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Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, especially in patients with recent percutaneous coronary intervention (PCI). We aimed to illustrate the types and timing of different surgeries occurring after PCI, and to evaluate the risk of thrombotic and bleeding events according to the perioperative antiplatelet management. Patients undergoing urgent or elective non-cardiac surgery within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, or stent thrombosis) at 30 days. Perioperative bleeding was defined as ≥ 2 units of blood transfusion. A total of 1092 surgeries corresponding to 747 patients were classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones, and were associated with an increased risk of both MACE and bleeding. Preoperative interruption of antiplatelet therapy (of any kind) occurred in 44.6% of all NCS and was more likely for procedures occurring later post-PCI and at intermediate risk. There was no significant association between interruption of antiplatelet therapy and adverse cardiac events. Among patients undergoing NCS within 1 year of PCI, perioperative ischemic and bleeding events primarily depend on the estimated surgical risk and urgency of the procedure, which are increased early after PCI. Preoperative antiplatelet interruption was not associated with an increased risk of cardiac events.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Daratumumab (DARA) is a monoclonal antibody for treatment of plasma cell myeloma targeting CD38, a surface molecule expressed on plasma cells and red blood cells (RBCs). This complicates blood bank testing, requiring dithiothreitol (DTT) to remove DARA interference. A simple in-house method of removing DARA interference without use of DTT, a potentially hazardous chemical, is desirable. We demonstrate a trypsin-based method to remove interference in antibody testing at a medical center (MC), with parallel testing at an immunohematology reference laboratory (IRL). STUDY DESIGN AND METHODS: Pre-DARA type and screen (T&S) samples were obtained from 61 patients for antibody testing and RBC phenotyping using untreated reagent RBCs. Subsequent post-DARA T&S testing was performed with untreated reagent RBCs to demonstrate interference and repeated after trypsin treatment. Positive trypsin-treated antibody screens were reflexed to antibody identification using trypsin-treated panel cells. Parallel testing was performed on the same post-DARA samples at IRL. RESULTS: DARA interference was detected in 61/61 (100%) samples by MC and IRL. After trypsin treatment, DARA interference was eliminated in 60/61 (98.4%) antibody screens by both institutions with an overall percent agreement of 96.7% (95% confidence interval [CI] 88.7%-99.6%). Identification of known alloantibodies was confirmed in 3/3 patients with 100% concordant results between MC and IRL. There were no false-negative results demonstrated by IRL's functionally CD38-negative controls. CONCLUSION: Our in-house trypsin-based method enables pretransfusion testing of patients receiving DARA in an accurate and cost-effective manner without missing clinically significant alloantibodies. This presents an additional testing option where DTT use is undesirable.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , ADP-Ribosil Ciclase 1/imunologia , Anticorpos Monoclonais/imunologia , Antineoplásicos/imunologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Humanos , Testes Imunológicos , Indicadores e Reagentes , Isoanticorpos/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologiaRESUMO
Patients with cirrhosis have coagulopathy often necessitating correction with blood products, such as plasma products (fresh frozen plasma and plasma frozen within 24âh) prior to certain invasive procedures. However, plasma administration has the potential for substantial negative adverse effects such as volume overload, transfusion-related lung injury and allergic/anaphylactic reactions. In addition, its effectiveness in preventing bleeding is similarly unclear. The purpose of this study was to determine the safety and efficacy of plasma administration in cirrhotic patients undergoing minimally invasive procedures, specifically vascular access placement, transjugular liver biopsies, renal biopsies and thoracenteses. In this retrospective cohort study, we identified patients receiving plasma products in preparation for an invasive procedure, with the primary outcomes of volume overload and bleeding. Of the 145 transfusion events that met the criteria from 2015 to 2018, the median INR decreased from 2.7 to 2.2 pre and post plasma administration and 13.8% of recipients had complications of volume overload. The cost of acquisition of plasma administered below clinically impactful doses accumulates to an estimated 19â000 dollars over this time period, not including nursing preparation or production costs. Plasma products minimally, if at all, improved laboratory values of coagulation and in some patients led to adverse effects.
Assuntos
Transfusão de Componentes Sanguíneos , Hemorragia/prevenção & controle , Cirrose Hepática/terapia , Procedimentos Cirúrgicos Minimamente Invasivos , Plasma , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Componentes Sanguíneos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Plasma/química , Estudos RetrospectivosRESUMO
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Through the length of the pandemic, the consortium has been a critical mechanism for sharing experience and best practices in dealing with issues including the following: instrument platforms, sample sources, test performance, pre- and post-analytical issues, supply chain, institutional testing capacity, pooled testing, biospecimen science, and research. The consortium also has been a mechanism for staying abreast of state and municipal policies and initiatives, and their impact on institutional and laboratory operations. The experience of this consortium may be of value to current and future laboratory professionals and policy-makers alike, in dealing with major events that impact regional laboratory services.
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As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections continue, there is a substantial need for cost-effective and large-scale testing that utilizes specimens that can be readily collected from both symptomatic and asymptomatic individuals in various community settings. Although multiple diagnostic methods utilize nasopharyngeal specimens, saliva specimens represent an attractive alternative as they can rapidly and safely be collected from different populations. While saliva has been described as an acceptable clinical matrix for the detection of SARS-CoV-2, evaluations of analytic performance across platforms for this specimen type are limited. Here, we used a novel sensitive RT-PCR/MALDI-TOF mass spectrometry-based assay (Agena MassARRAY®) to detect SARS-CoV-2 in saliva specimens. The platform demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of the platform and determined the limit of detection of the assay to be 1562.5 copies/ml. Furthermore, across the five individual target components of this assay, there was a range in analytic sensitivities for each target with the N2 target being the most sensitive. Overall, this system also demonstrated comparable performance when compared to the detection of SARS-CoV-2 RNA in saliva by the cobas® 6800/8800 SARS-CoV-2 real-time RT-PCR Test (Roche). Together, we demonstrate that saliva represents an appropriate matrix for SARS-CoV-2 detection on the novel Agena system as well as on a conventional real-time RT-PCR assay. We conclude that the MassARRAY® system is a sensitive and reliable platform for SARS-CoV-2 detection in saliva, offering scalable throughput in a large variety of clinical laboratory settings.
Assuntos
Teste de Ácido Nucleico para COVID-19/normas , COVID-19/diagnóstico , Testes Diagnósticos de Rotina/normas , RNA Viral/genética , SARS-CoV-2/genética , Saliva/virologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/normas , Benchmarking , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19/instrumentação , Teste de Ácido Nucleico para COVID-19/métodos , Testes Diagnósticos de Rotina/instrumentação , Testes Diagnósticos de Rotina/métodos , Humanos , Limite de Detecção , Nasofaringe/virologia , Manejo de Espécimes/normas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.
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COVID-19/fisiopatologia , Pulmão/fisiopatologia , Embolia Pulmonar/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Coagulação Sanguínea , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Causas de Morte , Citocinas/sangue , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Embolia Pulmonar/sangue , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , SARS-CoV-2/patogenicidadeRESUMO
Hospital acquired anemia (HAA) has been a recognized entity for nearly 50 years. Despite multiple hypotheses, a mechanistic understanding is lacking, and targeted interventions have not yet yielded significantly impactful results. Known risk factors include advanced age, multiple co-morbidities, low bone marrow reserve, admission to the intensive care unit, and frequent phlebotomy. However, confounding variables in many studies continues to complicate the identification of additional risk factors. Improved understanding of iron metabolism, erythropoiesis, and the erythroid iron restriction response in the last few decades, as well as the recent demonstration of poor outcomes correlating with increased transfusion have refocused attention on HAA. While retrospective database studies provide ample correlative data between 1) HAA and poor outcomes; 2) reduction of phlebotomy volume and decrease in transfusion requirement; and 3) over-transfusion and increased mortality, no causal link between reduced phlebotomy volume, decreased rates of HAA, and improved mortality or other relevant outcomes have been definitely established. Here, we review the current state of knowledge and provide a summary of potential directions to understand and mitigate HAA. There are at present no clear guidelines on whether and when to evaluate hospitalized patients for underlying causes of anemia. We thus provide a guide for clinicians in general practice toward identifying patients at the highest risk for HAA, decreasing blood loss through phlebotomy to the greatest degree feasible, and evaluating and treating reversible causes of anemia in a targeted population.
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Anemia/terapia , Anemia/epidemiologia , Anemia/metabolismo , Gerenciamento Clínico , Humanos , Doença Iatrogênica/epidemiologia , Ferro/metabolismo , Fatores de RiscoRESUMO
Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.
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Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/terapia , Testes de Neutralização , Ensaio de Imunoadsorção Enzimática , Humanos , Imunização Passiva , Soroterapia para COVID-19RESUMO
BACKGROUND: Convalescent plasma (CP) for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown preliminary signs of effectiveness in moderate to severely ill patients in reducing mortality. While studies have demonstrated a low risk of serious adverse events, the comprehensive incidence and nature of the spectrum of transfusion reactions to CP is unknown. We retrospectively examined 427 adult inpatient CP transfusions to determine incidence and types of reactions, as well as clinical parameters and risk factors associated with transfusion reactions. STUDY DESIGN AND METHODS: Retrospective analysis was performed for 427 transfusions to 215 adult patients with coronavirus 2019 (COVID-19) within the Mount Sinai Health System, through the US Food and Drug Administration emergency investigational new drug and the Mayo Clinic Expanded Access Protocol to Convalescent Plasma approval pathways. Transfusions were blindly evaluated by two reviewers and adjudicated by a third reviewer in discordant cases. Patient demographics and clinical and laboratory parameters were compared and analyzed. RESULTS: Fifty-five reactions from 427 transfusions were identified (12.9% incidence), and 13 were attributed to transfusion (3.1% incidence). Reactions were classified as underlying COVID-19 (76%), febrile nonhemolytic (10.9%), transfusion-associated circulatory overload (9.1%), and allergic (1.8%) and hypotensive (1.8%) reactions. Statistical analysis identified increased transfusion reaction risk for ABO blood group B or Sequential Organ Failure Assessment scores of 12 to 13, and decreased risk within the age group of 80 to 89 years. CONCLUSION: Our findings support the use of CP as a safe, therapeutic option from a transfusion reaction perspective, in the setting of COVID-19. Further studies are needed to confirm the clinical significance of ABO group B, age, and predisposing disease severity in the incidence of transfusion reaction events.
Assuntos
COVID-19/terapia , SARS-CoV-2/patogenicidade , Idoso , Transfusão de Sangue , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reação Transfusional , Soroterapia para COVID-19RESUMO
In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in China and has since caused a pandemic of coronavirus disease 2019 (COVID-19). The first case of COVID-19 in New York City was officially confirmed on 1 March 2020 followed by a severe local epidemic1. Here, to understand seroprevalence dynamics, we conduct a retrospective, repeated cross-sectional analysis of anti-SARS-CoV-2 spike antibodies in weekly intervals from the beginning of February to July 2020 using more than 10,000 plasma samples from patients at Mount Sinai Hospital in New York City. We describe the dynamics of seroprevalence in an 'urgent care' group, which is enriched in cases of COVID-19 during the epidemic, and a 'routine care' group, which more closely represents the general population. Seroprevalence increased at different rates in both groups; seropositive samples were found as early as mid-February, and levelled out at slightly above 20% in both groups after the epidemic wave subsided by the end of May. From May to July, seroprevalence remained stable, suggesting lasting antibody levels in the population. Our data suggest that SARS-CoV-2 was introduced in New York City earlier than previously documented and describe the dynamics of seroconversion over the full course of the first wave of the pandemic in a major metropolitan area.
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Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Teste Sorológico para COVID-19/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/imunologia , Monitoramento Epidemiológico , SARS-CoV-2/imunologia , Adolescente , Adulto , Assistência Ambulatorial/estatística & dados numéricos , COVID-19/diagnóstico , COVID-19/virologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVE: The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive. DESIGN: Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive. SETTING: All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system. PARTICIPANTS: Participants over the age of 18 years were included. PRIMARY OUTCOMES: We investigated in-hospital mortality during the study period. RESULTS: A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 µg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 µg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL. CONCLUSIONS: In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.
Assuntos
COVID-19/sangue , Cuidados Críticos , Mortalidade Hospitalar , Hospitalização , Pandemias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , COVID-19/epidemiologia , COVID-19/mortalidade , Comorbidade , Cuidados Críticos/estatística & dados numéricos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitais , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. METHODS: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. FINDINGS: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. INTERPRETATION: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. FUNDING: None.
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COVID-19 , Anticorpos Antivirais , COVID-19/diagnóstico , COVID-19/terapia , Humanos , Imunização Passiva , Cidade de Nova Iorque/epidemiologia , Reação em Cadeia da Polimerase , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus , Soroterapia para COVID-19RESUMO
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments1. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses2,3. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed1,2. This retrospective, propensity score-matched case-control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score-matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75-0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13-0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed.
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COVID-19/patologia , COVID-19/terapia , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pontuação de Propensão , Estudos Retrospectivos , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1ß in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
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Infecções por Coronavirus/imunologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Pneumonia Viral/imunologia , Fator de Necrose Tumoral alfa/imunologia , Idoso , Betacoronavirus , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Citocinas/imunologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , SARS-CoV-2 , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1ß in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.
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BACKGROUND: The coronavirus 2019 (Covid-19) pandemic is a global public health crisis, with over 1.6 million cases and 95,000 deaths worldwide. Data are needed regarding the clinical course of hospitalized patients, particularly in the United States. METHODS: Demographic, clinical, and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed Covid-19 between February 27 and April 2, 2020 were identified through institutional electronic health records. We conducted a descriptive study of patients who had in-hospital mortality or were discharged alive. RESULTS: A total of 2,199 patients with Covid-19 were hospitalized during the study period. As of April 2 nd , 1,121 (51%) patients remained hospitalized, and 1,078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 ug/ml, C-reactive protein was 162 mg/L, and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 ug/ml, C-reactive protein was 79 mg/L, and procalcitonin was 0.09 ng/mL. CONCLUSIONS: This is the largest and most diverse case series of hospitalized patients with Covid-19 in the United States to date. Requirement of intensive care and mortality were high. Patients who died typically had pre-existing conditions and severe perturbations in inflammatory markers.
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Daratumumab has proven to be highly efficacious for relapsed and refractory multiple myeloma (MM) and has recently been approved in the frontline setting for MM patients ineligible for transplantation. In the future, expanded indications are possible for daratumumab and other anti-CD38 monoclonal antibodies in development. For several years, it has been recognized that these therapies interfere with blood bank testing by binding to CD38 on red blood cells and causing panagglutination on the Indirect Antiglobulin Test. This can lead to redundant testing and significant delays in patient care. Given the anticipated increase in utilization of anti-CD38 monoclonal antibodies, as well as the transfusion needs of MM patients, it is critical to understand the nature of this interference with blood bank testing and to optimize clinical and laboratory procedures. In this review, we summarize the pathophysiology of this phenomenon, examine the clinical data reported to date, describe currently available methods to resolve this issue, and lastly provide a guide to clinical management of blood transfusions for patients receiving anti-CD38 monoclonal antibodies.
Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Transfusão de Sangue/métodos , Eritrócitos/metabolismo , Mieloma Múltiplo/terapia , ADP-Ribosil Ciclase 1/imunologia , Tipagem e Reações Cruzadas Sanguíneas , Teste de Coombs , Erros de Diagnóstico/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto , Ligação ProteicaRESUMO
Transfusion medicine (TM) physicians provide medical services that benefit all patients such as providing 24-hour laboratory coverage, advising health care providers on test interpretation and selection, validating new methods, and supervising technical personnel. These services ensure delivery of accurate, reliable, and timely laboratory test results and blood products. TM physicians also provide consultations to individual patients by 1) interpreting and determining the clinical significance of test results (e.g., alloantibodies, direct antiglobulin tests), 2) recommending appropriate component therapy and approving deviations from laboratory policy, and 3) evaluating and recommending treatment of suspected transfusion reactions. The potential benefits of consultations are improved quality and cost of health care, enhanced provider education, and decreased inappropriate testing and product utilization. When physician services are delivered to individual patients, are appropriately requested, provide a diagnosis or recommendation, and are properly documented, TM physicians can receive professional reimbursement. While many TM physicians provide medical direction and oversight of apheresis procedures, billing in this area is sufficiently complex to be reviewed elsewhere. The objective of this article is for educational purposes to describe the 1) benefits of a consultative TM service, 2) development of reimbursement systems in the United States for professional component services and the current regulatory requirements, 3) current procedural terminology codes commonly used for TM physician services, and 4) examples of consultation documentation and daily workflow at tertiary care teaching hospitals. The information provided should help guide physicians to deliver and bill for these services.
Assuntos
Bancos de Sangue , Médicos , Encaminhamento e Consulta , Bancos de Sangue/economia , Honorários e Preços , Humanos , Médicos/economia , Encaminhamento e Consulta/economia , Estados Unidos , Recursos HumanosRESUMO
Blood transfusion is the most common procedure in cardiac surgery. Increasing evidence exists that excess transfusions are harmful to patients. Transfusion reactions and complications, including infection, immune modulation, and lung injury, are known complications but underreported; hence, their significance is often disregarded. Furthermore, a number of randomized trials have shown that a restrictive transfusion strategy is equal to if not better than a liberal transfusion strategy. Despite the evidence for the use of restrictive transfusion triggers, its dissemination in the cardiac surgical community has met with resistance. In this review, we outline the risks of transfusion, compare restrictive and liberal transfusion strategies in cardiac surgery, and finally outline perioperative interventions to minimize transfusion in the cardiac surgical patient.