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1.
Am J Respir Crit Care Med ; 209(12): 1463-1476, 2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358857

RESUMO

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.


Assuntos
Rejeição de Enxerto , Transplante de Pulmão , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Rejeição de Enxerto/microbiologia , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Estudos Transversais , Adulto , Microbiota , RNA Ribossômico 16S/genética , Pulmão/microbiologia , Idoso , Doença Aguda
2.
Ann Pharmacother ; 57(1): 5-15, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35590468

RESUMO

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.


Assuntos
Tratamento Farmacológico da COVID-19 , Síndrome do Desconforto Respiratório , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Respiração Artificial , Corticosteroides/uso terapêutico , Dexametasona/uso terapêutico , Oxigênio
3.
Ann Pharmacother ; 56(3): 237-244, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34180274

RESUMO

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: 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: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE: 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.


Assuntos
Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19 , Insuficiência Respiratória , Adulto , COVID-19/mortalidade , Mortalidade Hospitalar , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/virologia , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Resultado do Tratamento
4.
Arterioscler Thromb Vasc Biol ; 40(11): 2586-2597, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32960072

RESUMO

The severe acute respiratory syndrome coronavirus-2 emerged as a serious human pathogen in late 2019, causing the disease coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is acute respiratory failure consistent with the acute respiratory distress syndrome. Airway, lung parenchymal, pulmonary vascular, and respiratory neuromuscular disorders all feature in COVID-19. This article reviews what is known about the effects of severe acute respiratory syndrome coronavirus-2 infection on different parts of the respiratory system, clues to understanding the underlying biology of respiratory disease, and highlights current and future translation and clinical research questions.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Pulmão/virologia , Pneumonia Viral/virologia , Respiração , Síndrome do Desconforto Respiratório/virologia , Insuficiência Respiratória/virologia , Pesquisa Translacional Biomédica , Animais , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/fisiopatologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Prognóstico , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Embolia Pulmonar/virologia , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Fatores de Risco , SARS-CoV-2 , Tromboembolia Venosa/fisiopatologia , Tromboembolia Venosa/terapia , Tromboembolia Venosa/virologia
5.
Crit Care ; 25(1): 311, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461959

RESUMO

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .


Assuntos
Embolia Pulmonar/terapia , Terapia Trombolítica/métodos , Embolectomia/métodos , Humanos , Unidades de Terapia Intensiva/organização & administração , Embolia Pulmonar/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Terapia Trombolítica/tendências
6.
J Thromb Thrombolysis ; 51(2): 330-338, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32910409

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism Response Teams (PERT) have previously been associated with improved outcomes. We aimed to investigate whether PERT utilization, recommendations, and outcomes for patients diagnosed with acute PE changed during the COVID-19 pandemic. This is a retrospective cohort study of all adult patients with acute PE who received care at an academic hospital system in New York City between March 1st and April 30th, 2020. These patients were compared against historic controls between March 1st and April 30th, 2019. PE severity, PERT utilization, initial management, PERT recommendations, and outcomes were compared. There were more cases of PE during the pandemic (82 vs. 59), but less PERT activations (26.8% vs. 64.4%, p < 0.001) despite similar markers of PE severity. PERT recommendations were similar before and during the pandemic; anticoagulation was most recommended (89.5% vs. 86.4%, p = 0.70). During the pandemic, those with PERT activations were more likely to be female (63.6% vs. 31.7%, p = 0.01), have a history of DVT/PE (22.7% vs. 1.7%, p = 0.01), and to be SARS-CoV-2 PCR negative (68.2% vs. 38.3% p = 0.02). PERT activation during the pandemic is associated with decreased length of stay (7.7 ± 7.7 vs. 13.2 ± 12.7 days, p = 0.02). PERT utilization decreased during the COVID-19 pandemic and its activation was associated with different biases. PERT recommendations and outcomes were similar before and during the pandemic, and led to decreased length of stay during the pandemic.


Assuntos
Anticoagulantes/administração & dosagem , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospitais Universitários , Pandemias , Embolia Pulmonar , SARS-CoV-2/metabolismo , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Guias de Prática Clínica como Assunto , Embolia Pulmonar/sangue , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Crit Care Med ; 48(9): 1319-1326, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32618696

RESUMO

OBJECTIVES: The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk. We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states. DESIGN: Retrospective. SETTING: Tertiary ICU in New York City. PATIENTS: Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 3.05). Reaction time and K values were below the lower limit of normal in 43.8% of the population consistent with a hypercoagulable profile. The median α angle and maximum amplitude (75.8° and 72.8 mm, respectively) were in the hypercoagulable range. The α angle was above reference range in 70.3% of patients indicative of rapid clot formation. Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 60.1% of patients. Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort. Those with D-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with D-dimer levels less than or equal to 2,000 (4.8 vs 5.6 min; p = 0.001). CONCLUSIONS: A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function. As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Tromboelastografia , Trombofilia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Estado Terminal , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Valores de Referência , Estudos Retrospectivos , SARS-CoV-2 , Trombofilia/diagnóstico , Trombose/etiologia
8.
Vasc Med ; 25(2): 133-140, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31709912

RESUMO

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


Assuntos
Ecocardiografia Doppler de Pulso , Embolia Pulmonar/diagnóstico por imagem , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Adulto , Idoso , Feminino , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudo de Prova de Conceito , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Choque Cardiogênico/terapia , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia
11.
Diabetes Care ; 47(11): 1930-1940, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39287394

RESUMO

OBJECTIVE: Studies show metformin use before and during SARS-CoV-2 infection reduces severe COVID-19 and postacute sequelae of SARS-CoV-2 (PASC) in adults. Our objective was to describe the incidence of PASC and possible associations with prevalent metformin use in adults with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This is a retrospective cohort analysis using the National COVID Cohort Collaborative (N3C) and Patient-Centered Clinical Research Network (PCORnet) electronic health record (EHR) databases with an active comparator design that examined metformin-exposed individuals versus nonmetformin-exposed individuals who were taking other diabetes medications. T2DM was defined by HbA1c ≥6.5 or T2DM EHR diagnosis code. The outcome was death or PASC within 6 months, defined by EHR code or computable phenotype. RESULTS: In the N3C, the hazard ratio (HR) for death or PASC with a U09.9 diagnosis code (PASC-U09.0) was 0.79 (95% CI 0.71-0.88; P < 0.001), and for death or N3C computable phenotype PASC (PASC-N3C) was 0.85 (95% CI 0.78-0.92; P < 0.001). In PCORnet, the HR for death or PASC-U09.9 was 0.87 (95% CI 0.66-1.14; P = 0.08), and for death or PCORnet computable phenotype PASC (PASC-PCORnet) was 1.04 (95% CI 0.97-1.11; P = 0.58). Incident PASC by diagnosis code was 1.6% metformin vs. 2.0% comparator in the N3C, and 2.1% metformin vs. 2.5% comparator in PCORnet. By computable phenotype, incidence was 4.8% metformin and 5.2% comparator in the N3C and 24.7% metformin vs. 26.1% comparator in PCORnet. CONCLUSIONS: Prevalent metformin use is associated with a slightly lower incidence of death or PASC after SARS-CoV-2 infection. PASC incidence by computable phenotype is higher than by EHR code, especially in PCORnet. These data are consistent with other observational analyses showing prevalent metformin is associated with favorable outcomes after SARS-CoV-2 infection in adults with T2DM.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Registros Eletrônicos de Saúde , Hipoglicemiantes , Metformina , Humanos , Metformina/uso terapêutico , COVID-19/epidemiologia , COVID-19/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Hipoglicemiantes/uso terapêutico , Incidência , Adulto , SARS-CoV-2 , Estudos de Coortes
12.
ERJ Open Res ; 10(4)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978558

RESUMO

Introduction: Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study. Material and methods: We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load. Results: While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p<0.05), while there was no such association with antibody levels in the systemic circulation. Discussion: Our data highlight the critical role of local adaptive immunity in the airways as a key defence mechanism against primary SARS-CoV-2 infection.

13.
Crit Care Explor ; 5(1): e0828, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36699257

RESUMO

Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENTS: We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1-20.3 hr) in the early group versus 33.4 (27.9-41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6-20 mm Hg] vs 6 mm Hg [1-10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523). CONCLUSIONS: Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.

14.
J Crit Care ; 76: 154291, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37043893

RESUMO

PURPOSE: Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. MATERIALS/METHODS: A retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. RESULTS: A total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. CONCLUSION: Compared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.


Assuntos
COVID-19 , Insuficiência Respiratória , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Resultado do Tratamento , Tratamento Farmacológico da COVID-19 , Insuficiência Respiratória/tratamento farmacológico
15.
J Crit Care ; 77: 154344, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37244209

RESUMO

PURPOSE: The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19. MATERIALS AND METHODS: We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered. RESULTS: Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53). CONCLUSION: This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.


Assuntos
COVID-19 , Neoplasias , Tromboembolia Venosa , Humanos , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Estado Terminal , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Tromboembolia Venosa/tratamento farmacológico
16.
Sleep ; 46(9)2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37166330

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS: We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS: Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS: Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.


Assuntos
COVID-19 , Apneia Obstrutiva do Sono , Adulto , Humanos , Criança , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Registros Eletrônicos de Saúde , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Progressão da Doença , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
17.
PLoS One ; 18(6): e0286297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37352211

RESUMO

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Estudos Observacionais como Assunto , Síndrome de COVID-19 Pós-Aguda , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Adolescente , Adulto , Estudos Multicêntricos como Assunto
18.
ATS Sch ; 3(4): 522-534, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36726709

RESUMO

With growing patient complexity, the cardiovascular intensive care unit (CICU) of today has evolved substantially from the coronary care unit (CCU) of decades ago. The growing burden of noncardiac critical illness and highly specialized acute cardiovascular disease requires a degree of expertise beyond that afforded through a general cardiology training program. Therefore, the American Heart Association (AHA) has proposed a CICU staffing model to include dedicated cardiac intensivists; in the present day, "dual-trained" physicians are extremely sparse. Guidance on designing critical care fellowships for cardiologists is limited but will require collaboration between cardiologists and medical intensivists. Here, we review the evolution of the CICU, describe training pathways, and offer guidance on creating a cardiology critical care training program.

19.
Ann N Y Acad Sci ; 1507(1): 49-59, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060087

RESUMO

Cardiac arrest has many implications for morbidity and mortality. Few interventions have been shown to improve return of spontaneous circulation (ROSC) and long-term outcomes after cardiac arrest. Ischemic-reperfusion injury upon achieving ROSC creates an imbalance between oxygen supply and demand. Multiple events occur in the postcardiac arrest period, including excitotoxicity, mitochondrial dysfunction, and oxidative stress and inflammation, all of which contribute to ongoing brain injury and cellular death. Given that complex pathophysiology underlies global brain hypoxic ischemia, neuroprotective strategies targeting multiple stages of the neuropathologic cascade should be considered as a means of mitigating secondary neuronal injury and improving neurologic outcomes and survival in cardiac arrest victims. In this review article, we discuss a number of different pharmacologic agents that may have a potential role in targeting these injurious pathways following cardiac arrest. Pharmacologic therapies most relevant for discussion currently include memantine, perampanel, magnesium, propofol, thiamine, methylene blue, vitamin C, vitamin E, coenzyme Q10 , minocycline, steroids, and aspirin.


Assuntos
Lesões Encefálicas/prevenção & controle , Isquemia Encefálica/prevenção & controle , Parada Cardíaca/tratamento farmacológico , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Isquemia Encefálica/etiologia , Isquemia Encefálica/metabolismo , Parada Cardíaca/complicações , Parada Cardíaca/metabolismo , Humanos , Memantina/administração & dosagem , Neuroproteção/fisiologia , Nitrilas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Piridonas/administração & dosagem , Tiamina/administração & dosagem
20.
J Invasive Cardiol ; 34(1): E32-E38, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34866048

RESUMO

BACKGROUND: The initial wave of the coronavirus disease 2019 (COVID-19) pandemic resulted in an influx of patients with acute viral illness and profound changes in healthcare delivery in New York City. The impact of this pandemic on the presentation and invasive management of acute myocardial infarction (MI) is not well described. METHODS: This single-center retrospective study compared patients with MI who underwent invasive coronary angiography at New York University from March-April 2020, during the peak of the first wave of the pandemic, with those presenting in March-April 2019. RESULTS: Only 35 patients with MI underwent angiography during the study period in 2020 vs 109 patients in 2019. No differences in comorbidities or baseline medications were identified. The proportion of patients with ST-segment elevation MI (STEMI) was higher in 2020 than in 2019 (48.6% vs 24.8%, respectively; P=.01). Median peak troponin concentration was higher (14.5 ng/mL vs 2.9 ng/mL; P<.01) and left ventricular ejection fraction was lower (43.34% vs 51.1%; P=.02) during the pandemic. Among patients with non-STEMI, time from symptom onset to presentation was delayed in 2020 compared with 2019 (median, 24 hours vs 10 hours; P=.04). CONCLUSION: There was a dramatic decrease in the number of patients with MI undergoing coronary angiography during the first wave of the COVID-19 pandemic. Of those who presented, patients tended to seek care later after symptom onset and had excess myocardial injury. These data indicate a need for improved patient education to ensure timely cardiovascular care during public health emergencies.


Assuntos
COVID-19 , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Cidade de Nova Iorque , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Volume Sistólico , Função Ventricular Esquerda
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