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1.
Medicine (Baltimore) ; 99(43): e22812, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120803

RESUMO

INTRODUCTION: Legionnaires' disease is caused by Legionella bacteria, and commonly manifests as pneumonia and has a high fatality rate. PATIENT CONCERNS: This case study reports on the fatal incident of a patient, initially diagnosed with pneumonia, and subsequently diagnosed with Legionnaires' disease caused by a new sequence type (ST) of Legionella. DIAGNOSIS: It is speculated that the patient acquired Legionnaires' disease from a contaminated water source. Legionnaires' disease was diagnosed using the Legionella urinary antigen assay and bacterial cultures of respiratory secretions; Legionella pneumophilia Type 1 was also identified through serological testing. Sequence-based typing of the cultured bacterium revealed it to be a previously unidentified species, and it was named ST2345 new-type. INTERVENTIONS: In addition to the treatment of Legionnaires' disease, blood samples taken on the second day of admission showed a co-infection of Candida tropicalis, which was treated with anti-fungal treatment. The patient improved after a week, however, on the seventh day of administration lower respiratory secretions showed the growth of Klebsiella pneumonia, indicative of ventilator-associated pneumonia. OUTCOMES: Despite active treatment, the patient passed away due to multiple organ failure. As this was a fatal case, further research is needed to determine whether the critical condition of this case was related to the virulence of the novel Legionella strain. CONCLUSION: A key finding of this study is that treatment for suspected Legionnaires' disease must be administered rapidly, as infection with Legionella may give rise to secondary pathogenic infections.


Assuntos
Legionella pneumophila/genética , Doença dos Legionários/complicações , Insuficiência de Múltiplos Órgãos/etiologia , Humanos , Doença dos Legionários/terapia , Masculino , Pessoa de Meia-Idade , Sorogrupo
2.
Fa Yi Xue Za Zhi ; 36(4): 525-530, 2020 Aug.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33047538

RESUMO

Abstract: Objective To investigate the epidemiological and forensic characteristics of multiple organ dysfunction syndrome (MODS) after severe trauma and explore the reference indexes for determining traumatic MODS. Methods In terms of the number of organs or systems involved in MODS, the number of failures of each organ or system, the first failing organ and the survival time after organ failure, 72 cases of MODS death caused by traffic accidents were retrospectively analyzed. The cases were divided into two groups according to the mean injury severity score (ISS). The t test was used to analyze the differences in the number of organs or systems involved in MODS in the two groups. Chi-square test was used to analyze the differences in the types of first failing organs and the differences between the two groups in the number of cases of organ or system failure involved in MODS. Wilcoxon signed-rank test was used to analyze the differences between the two groups in survival time of MODS after trauma. Kaplan-Meier survival curve was drawn and Log-Rank test was performed. Results The number of MODS involved organs or systems after trauma in ISS≤35 group was 3-5, and 2-4 in the ISS>35 group (P<0.05). The cases of MODS organ or system failure after trauma occurred more in brain and lung in the two groups. The first failing organ after trauma was mainly the lung or kidney. The median time of first organ failure after trauma was 2.00 d, the median survival time of MODS after trauma in ISS≤35 group was 6.00 d, and 2.33 d in ISS>35 group (P<0.05). The survival curve of ISS≤35 group was relatively high and declined gradually, while the survival curve of ISS>35 group was relatively low and the decline was steep (P<0.05). Conclusion The epidemiological and forensic characteristics of MODS caused by traffic accidents have certain specificity. The ISS and the forensic characteristics of MODS at ISS>35 can be used as reliable reference indexes for evaluation of the causal relationship among trauma, MODS and death.


Assuntos
Insuficiência de Múltiplos Órgãos , Ferimentos e Lesões , Acidentes de Trânsito , Humanos , Escala de Gravidade do Ferimento , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Ferimentos e Lesões/complicações
4.
Medicine (Baltimore) ; 99(42): e22793, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080751

RESUMO

RATIONALE: Thrombocytepenia, anasarca, fever, renal insufficiency, and organomegaly (TAFRO) syndrome is a novel disease entity characterized by a constellation of symptoms (thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly). Here, we describe the development of TAFRO syndrome-like features during the treatment of rheumatoid arthritis with a Janus kinase (JAK) inhibitor. PATIENT CONCERNS: In this report, a 74-year-old woman treated with a JAK inhibitor (tofacitinib) for rheumatoid arthritis was admitted because of fever and thrombocytopenia. DIAGNOSES: On laboratory examination, marked thrombocytopenia and elevated creatinine and C-reactive protein levels were present. A computed tomography scan revealed lymphadenopathy, hepato-splenomegaly, and anasarca. A left axillary lymph node biopsy revealed Castleman's disease-like features. These clinical features satisfied the proposed diagnostic criteria for TAFRO syndrome. Since autoimmune disorders should be excluded when diagnosing TAFRO syndrome, it is not strictly correct to diagnose her as TAFRO syndrome. Therefore, we diagnosed her as rheumatoid arthritis complicated by TAFRO syndrome-like features. INTERVENTIONS: The patient was treated with high-dose glucocorticoid, tacrolimus, eltrombopag, intravenous immunoglobulin, and rituximab. OUTCOMES: Her condition was refractory to the above-mentioned treatment, and she eventually died because of multi-organ failure 6 months after the first admission. LESSONS: TAFRO syndrome-like features can develop during treatment with a JAK inhibitor for rheumatoid arthritis. Patients with autoimmune diseases complicated by TAFRO syndrome-like features can follow a fatal clinical course, and thus, an intensive combined treatment is warranted for such patients, especially in cases refractory to glucocorticoid.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/induzido quimicamente , Inibidores de Janus Quinases/efeitos adversos , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Trombocitopenia/induzido quimicamente , Idoso , Evolução Fatal , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/etiologia
5.
Mediators Inflamm ; 2020: 8198963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029105

RESUMO

The novel coronavirus is not only causing respiratory problems, but it may also damage the heart, kidneys, liver, and other organs; in Wuhan, 14 to 30% of COVID-19 patients have lost their kidney function and now require either dialysis or kidney transplants. The novel coronavirus gains entry into humans by targeting the ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, and this leads to hyperinflammation, forcing the immune cells to destroy healthy cells. This is why some COVID-19 patients need intensive care. The inflammatory chemicals released during COVID-19 infection cause the liver to produce proteins that defend the body from infections. However, these proteins can cause blood clotting, which can clog blood vessels in the heart and other organs; as a result, the organs are deprived of oxygen and nutrients which could ultimately lead to multiorgan failure and consequent progression to acute lung injury, acute respiratory distress syndrome, and often death. However, there are novel protein modification tools called the QTY code, which are similar in their structure to antibodies, which could provide a solution to excess cytokines. These synthetic proteins can be injected into the body to bind the excess cytokines created by the cytokine storm; this will eventually remove the excessive cytokines and inhibit the severe symptoms caused by the COVID-19 infection. In this review, we will focus on cytokine storm in COVID-19 patients, their impact on the body organs, and the potential treatment by QTY code-designed detergent-free chemokine receptors.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Receptores de Quimiocinas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Citocinas/antagonistas & inibidores , Desenho de Fármacos , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Modelos Moleculares , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/terapia , Pandemias , Pneumonia Viral/terapia , Engenharia de Proteínas , Modificação Traducional de Proteínas , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo
6.
BMC Surg ; 20(1): 224, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023552

RESUMO

BACKGROUND: Immunosuppressed patients, including individuals with organ transplantation, have been among susceptible groups with regard to COVID-19, on the other hand pediatric patients more commonly undergo a mild clinical course after acquiring COVID-19. To the best of the authors knowledge, to this date very little data exists on COVID-19 in a pediatric patient with liver transplantation. CASE PRESENTATION: We report a three year-old boy who had liver transplantation at 18 months old. He was admitted due to dyspnea with impression of acute respiratory distress syndrome and was then transferred to the intensive care unit. Chest X-ray at admission showed bilateral infiltration. Vancomycin, meropenem, azithromycin, voriconazole and co-trimoxazole were started from the first day of admission. On day 4 of admission, with suspicion of COVID-19, hydroxychloroquine, lopinavir/ritonavir and oseltamivir were added to the antibiotic regimen. PCR was positive for COVID-19. The patient developed multi-organ failure and died on day 6 of admission. CONCLUSIONS: For pediatric patients with organ transplantations, extreme caution should be taken, to limit and prevent their contact with COVID-19 during the outbreak, as these patients are highly susceptible to severe forms of the disease.


Assuntos
Infecções por Coronavirus/complicações , Transplante de Fígado , Insuficiência de Múltiplos Órgãos/etiologia , Pneumonia Viral/complicações , Pré-Escolar , Humanos , Unidades de Terapia Intensiva , Masculino , Pandemias
7.
Pediatr Crit Care Med ; 21(11): e1031-e1037, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32886460

RESUMO

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.


Assuntos
Infecções por Coronavirus/complicações , Pediatria/normas , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto , Sepse/terapia , Algoritmos , Atitude Frente a Saúde , Betacoronavirus , Criança , Cuidados Críticos/normas , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/terapia , Pandemias , Ressuscitação/normas , Sepse/etiologia , Choque Séptico/etiologia , Choque Séptico/terapia , Vasoconstritores/uso terapêutico
8.
Life Sci ; 260: 118431, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946915

RESUMO

Coronavirus disease 2019 (COVID-19) is a prominent pandemic disease that emerged in China and hurriedly stretched worldwide. There are many reports on COVID-19 associated with the amplified incidence of thrombotic events. In this review, we focused on COVID-19 coupled with the coagulopathy contributes to severe outcome inclusive of comorbidities such as venous thromboembolism, stroke, diabetes, lung, heart attack, AKI, and liver injury. Initially, the COVID-19 patient associated coagulation disorders show an elevated level of the D-dimer, fibrinogen, and less lymphocyte count such as lymphopenia. COVID-19 associated with the Kawasaki disease has acute vasculitis in childhood which further affects the vessels found all over the body. COVID-19 linked with the thrombotic microangiopathy triggers the multiple vasculitis along with the arterioles thrombosis, medium, large venous and arterial vessels mediates the disseminated intravascular coagulation (DIC). SARS-Co-V-2 patients have reduced primary platelet production, increased destruction of the platelet, decreased circulating platelet leads to the condition of increased thrombocytopenia which contributes to the coagulation disorder. Endothelial dysfunction plays an important role in the coagulation disorders via increased generation of the thrombin and stops fibrinolysis further leads to hypercoagulopathy. Along with that endothelial dysfunction activates the complement system pathways and contributes to the acute and chronic inflammation via cytokine storm with the production of the cytokines and chemokines, coagulation in different organs such as lung, brain, liver, heart, kidney and further leads to multi-organ failure.


Assuntos
Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Insuficiência de Múltiplos Órgãos/etiologia , Pneumonia Viral/complicações , Transtornos da Coagulação Sanguínea/patologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico
9.
Rev Paul Pediatr ; 38: e2020165, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32876282

RESUMO

OBJECTIVE: Recently, there have been reports of children with severe inflammatory syndrome and multiorgan dysfunction associated with elevated inflammatory markers. These cases are reported as presenting the Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. In this study, we describe with parental permission a case of MIS-C in an infant with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE DESCRIPTION: A seven-month-old infant, with SARS-CoV-2 infection and a history of extreme preterm birth and very low weight at birth, with an initial course of mild respiratory symptoms and abrupt progression to vasoplegic shock, myocarditis and hyperinflammation syndrome, shown by high levels of troponin I, ferritin, CRP, D-dimer and hypoalbuminemia. Despite the intensive care provided, the child developed multiple organ dysfunction and died. COMMENTS: Patients with a history of extreme prematurity may present with MIS-C in the presence of COVID-19 and are a group of special concern.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Insuficiência de Múltiplos Órgãos , Pandemias , Pneumonia Viral , Ressuscitação , Choque , Síndrome de Resposta Inflamatória Sistêmica , Deterioração Clínica , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Evolução Fatal , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Recém-Nascido , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/terapia , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Nascimento Prematuro , Respiração Artificial/métodos , Ressuscitação/métodos , Fatores de Risco , Choque/etiologia , Choque/terapia , Síndrome de Resposta Inflamatória Sistêmica/terapia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Tomografia Computadorizada por Raios X/métodos
10.
Eur Rev Med Pharmacol Sci ; 24(16): 8606-8620, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32894568

RESUMO

OBJECTIVE: COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection. Pathobiological transitions and clinical stages of the COVID-19 syndrome following the attack of SARS-CoV-2 on the human body have not been fully explored. The aim of this review is to outline the three critical prominent phase regarding the clinicogenomics course of the COVID-19 immune syndrome. MATERIALS AND METHODS: In the clinical setting, the COVID-19 process presents as "asymptomatic/pre-symptomatic phase", "respiratory phase with mild/moderate/severe symptoms" and "multi-systemic clinical syndrome with impaired/disproportionate and/or defective immunity". The corresponding three genomic phases include the "ACE2, ANPEP transcripts in the initial phase", "EGFR and IGF2R transcripts in the propagating phase" and the "immune system related critical gene involvements of the complicating phase". RESULTS: The separation of the phases is important since the genomic features of each phase are different from each other and these different mechanisms lead to distinct clinical multi-systemic features. Comprehensive genomic profiling with next generation sequencing may play an important role in defining and clarifying these three unique separate phases for COVID-19. From our point of view, it is important to understand these unique phases of the syndrome in order to approach a COVID-19 patient bedside. CONCLUSIONS: This three-phase approach may be useful for future studies which will focus on the clinical management and development of the vaccines and/or specific drugs targeting the COVID-19 processes. ANPEP gene pathway may have a potential for the vaccine development. Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course. Moreover, future CRISPR technology can be utilized for the genomic editing and future management of the clinical course of the syndrome.


Assuntos
Doenças Assintomáticas , Infecções por Coronavirus/patologia , Sistema Imunitário/metabolismo , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação da Expressão Gênica , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Prognóstico , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismo , Sepse/complicações , Sepse/patologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32968029

RESUMO

In this report, we describe the case of a 17-year-old boy with progressive respiratory failure requiring extracorporeal support who met clinical criteria for a presumptive diagnosis of electronic cigarette or vaping-associated acute lung injury (EVALI), with clinical, pathologic, and laboratory evidence of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). The patient in our report had a history of tetrahydrocannabinol and nicotine electronic cigarette use for months leading up to his presentation of fever, headache, emesis, and weight loss with respiratory distress. Multiple potential diagnoses were explored, and the patient's respiratory status improved, and he was initially discharged from the hospital. Roughly one week later, the patient was readmitted for worsening respiratory distress. The patient then met sufficient criteria for a potential diagnosis of HLH and MAS (elevated ferritin level, inflammatory markers, and cytopenia) to warrant a bone marrow aspirate, which revealed rare hemophagocytic cells. Given the severity of his symptoms and laboratory evidence of HLH and MAS, the patient was started on a course of steroids and anakinra. Although laboratory markers improved after treatment, the patient's respiratory failure worsened, ultimately progressing to a need for mechanical ventilation and extracorporeal support and leading to worsening multiorgan system failure and, ultimately, death. To the best of our knowledge, this is the first report of a patient with a presumptive diagnosis of EVALI with evidence of HLH and MAS, raising the possibility that macrophage activation may play a role in the pathogenesis of EVALI.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Sistemas Eletrônicos de Liberação de Nicotina , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Vaping/efeitos adversos , Adolescente , Evolução Fatal , Humanos , Síndrome de Ativação Macrofágica/induzido quimicamente , Masculino , Insuficiência de Múltiplos Órgãos/etiologia
13.
Mol Neurobiol ; 57(12): 4921-4928, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32813238

RESUMO

The global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore and examine the possible links between COVID-19 and ischemic stroke (IS). Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. The swift increase in the knowledge of SARS-CoV-2 has given creditable evidence that SARS-CoV-2 infected patients also encounter neurological deficits. As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra. The COVID-19 pandemic has affected people with various pre-existing diseases, including IS, in such a way that these patients need special care and attention for their survival. Several clinical trials are currently ongoing worldwide as well as many other projects are in different stages of conceptualization and planning to facilitate the effective management of stroke patients with COVID-19 infection.


Assuntos
Betacoronavirus , Isquemia Encefálica/etiologia , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Acidente Vascular Cerebral/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Barreira Hematoencefálica , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Quimiotaxia de Leucócito , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Encefalite Viral/complicações , Encefalite Viral/fisiopatologia , Hemodinâmica , Humanos , Inflamação , Modelos Imunológicos , Modelos Neurológicos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Receptores Virais/fisiologia , Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia
15.
JAMA ; 324(7): 642-650, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32809003

RESUMO

Importance: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. Objective: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. Design, Setting, and Participants: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. Interventions: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). Main Outcomes and Measures: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. Results: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). Conclusions and Relevance: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. Trial Registration: ClinicalTrials.gov Identifier: NCT03389555.


Assuntos
Corticosteroides/uso terapêutico , Ácido Ascórbico/uso terapêutico , Insuficiência de Múltiplos Órgãos/prevenção & controle , Choque Séptico/tratamento farmacológico , Tiamina/uso terapêutico , Corticosteroides/efeitos adversos , Adulto , Idoso , Ácido Ascórbico/efeitos adversos , Infecção Hospitalar , Quimioterapia Combinada , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hipernatremia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Escores de Disfunção Orgânica , Modelos de Riscos Proporcionais , Choque Séptico/complicações , Tiamina/efeitos adversos , Falha de Tratamento
16.
Chem Biol Interact ; 329: 109220, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32763245

RESUMO

The sepsis is considered as serious clinic-pathological condition related with high rate of morbidity and mortality in critical care settings. In the proposed study, the hydrazides derivatives N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) were investigated against the LPS-induced sepsis in rodents. The NCHDH and NTHDH markedly improved the physiological sign and symptoms associated with the sepsis such as mortality, temperature, and clinical scoring compared to negative control group, which received only LPS (i.p.). The NCHDH and NTHDH also inhibited the production of the NO and MPO compared to the negative control. Furthermore, the treatment control improved the histological changes markedly of all the vital organs. Additionally, the Masson's trichrome and PAS (Periodic Acid Schiff) staining also showed improvement in the NCHDH and NTHDH treated group in contrast to LPS-induced group. The antioxidants were enhanced by the intervention of the NCHDH and NTHDH and the level of the MDA and POD were attenuated marginally compared to the LPS-induced group. The hematology study showed marked improvement and the reversal of the LPS-induced changes in blood composition compared to the negative control. The synthetic function of the liver and kidney were preserved in the NCHDH and NTHDH treated group compared to the LPS-induced group. The NCHDH and NTHDH markedly enhanced the Nrf2, HO-1 (Heme oxygenase-1), while attenuated the Keap1 and TRPV1 expression level as compared to LPS treated group. Furthermore, the NCHDH and NTHDH treatment showed marked increased in the mRNA expression level of the HSP70/90 proteins compared to the negative control.


Assuntos
Hidrazinas/farmacologia , Insuficiência de Múltiplos Órgãos/etiologia , Sepse/etiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Heme Oxigenase-1/metabolismo , Hidrazinas/química , Hidrazinas/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/mortalidade , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Sepse/tratamento farmacológico , Sepse/mortalidade , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
17.
Stroke ; 51(9): 2674-2682, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32755348

RESUMO

BACKGROUND AND PURPOSE: No studies have reported the effect of the coronavirus disease 2019 (COVID-19) epidemic on patients with preexisting stroke. We aim to study the clinical course of COVID-19 patients with preexisting stroke and to investigate death-related risk factors. METHODS: We consecutively included 651 adult inpatients with COVID-19 from the Central Hospital of Wuhan between January 2 and February 15, 2020. Data on the demography, comorbidities, clinical manifestations, laboratory findings, treatments, complications, and outcomes (ie, discharged or death) of the participants were extracted from electronic medical records and compared between patients with and without preexisting stroke. The association between risk factors and mortality was estimated using a Cox proportional hazards regression model for stroke patients infected with severe acute respiratory syndrome coronavirus 2. RESULTS: Of the 651 patients with COVID-19, 49 with preexisting stroke tended to be elderly, male, had more underlying comorbidities and greater severity of illness, prolonged length of hospital stay, and greater hospitalization expenses than those without preexisting stroke. Cox regression analysis indicated that the patients with stroke had a higher risk of developing critical pneumonia (adjusted hazard ratio, 2.01 [95% CI, 1.27-3.16]) and subsequent mortality (adjusted hazard ratio, 1.73 [95% CI, 1.00-2.98]) than the patients without stroke. Among the 49 stroke patients, older age and higher score of Glasgow Coma Scale or Sequential Organ Failure Assessment were independent risk factors associated with in-hospital mortality. CONCLUSIONS: Preexisting stroke patients infected with severe acute respiratory syndrome coronavirus 2 were readily predisposed to death, providing an important message to individuals and health care workers that preventive measures must be implemented to protect and reduce transmission in stroke patients in this COVID-19 crisis.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Comorbidade , Infecções por Coronavirus/terapia , Progressão da Doença , Registros Eletrônicos de Saúde , Feminino , Escala de Coma de Glasgow , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Pandemias , Pneumonia/etiologia , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
18.
Am J Case Rep ; 21: e925020, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32661220

RESUMO

BACKGROUND C-reactive protein (CRP) plasma levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel viral disease, are surprisingly high. Pulmonary inflammation with subsequent fibrosis in SARS-CoV-2 infection is strongly accelerated. Recently, we have developed CRP apheresis to selectively remove CRP from human plasma. CRP may contribute to organ failure and pulmonary fibrosis in SARS-CoV-2 infection by CRP-mediated complement and macrophage activation. CASE REPORT A 72-year-old male patient at high risk was referred with dyspnea and fever. Polymerase chain reaction analysis of throat smear revealed SARS-CoV-2 infection. CRP levels were ~200 mg/L. Two days after admission, CRP apheresis using the selective CRP adsorber (PentraSorb® CRP) was started. CRP apheresis was performed via peripheral venous access on days 2, 3, 4, and 5. Following a 2-day interruption, it was done via central venous access on days 7 and 8. Three days after admission the patient was transferred to the intensive care unit and intubated due to respiratory failure. Plasma CRP levels decreased by ~50% with peripheral (processed blood plasma ≤6000 mL) and by ~75% with central venous access (processed blood plasma ≤8000 mL), respectively. No apheresis-associated side effects were observed. After the 2-day interruption in apheresis, CRP levels rapidly re-increased (>400 mg/L) and the patient developed laboratory signs of multi-organ failure. When CRP apheresis was restarted, CRP levels and creatinine kinases (CK/CK-MB) declined again. Serum creatinine remained constant. Unfortunately, the patient died of respiratory failure on day 9 after admission. CONCLUSIONS This is the first report on CRP apheresis in a SARS-CoV-2 patient. SARS-CoV-2 may cause multi-organ failure in part by inducing an excessive CRP-mediated autoimmune response of the ancient innate immune system.


Assuntos
Betacoronavirus , Remoção de Componentes Sanguíneos/métodos , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/terapia , Insuficiência de Múltiplos Órgãos/terapia , Pneumonia Viral/terapia , Idoso , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações
19.
Med Sci Monit ; 26: e925047, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32720649

RESUMO

BACKGROUND The aim of this study was to describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and compare these parameters in an elderly group with those in a younger group. MATERIAL AND METHODS This retrospective, single-center observational study included 69 hospitalized patients with laboratory-confirmed COVID-19 from a tertiary hospital in Wuhan, China, between January 14, 2020, and February 26, 2020. Epidemiological, demographic, clinical, and laboratory data, as well as treatments, complications, and outcomes were extracted from electronic medical records and compared between elderly patients (aged ≥60 years) and younger patients (aged <60 years). Patients were followed until March 19, 2020. RESULTS Elderly patients had more complications than younger patients, including acute respiratory distress syndrome (ARDS; 9/25, 36% vs. 5/44, 11.4%) and cardiac injury (7/25, 28% vs. 1/44, 2.3%), and they were more likely to be admitted to the intensive care unit (6/25, 24% vs. 2/44, 4.5%). As of March 19, 2020, 60/69 (87%) of the patients had been discharged, 6/69 (8.7%) had died, and 3/69 (4.3%) remained in the hospital. Of those who were discharged or died, the median duration of hospitalization was 13.5 days (interquartile range, 10-18 days). CONCLUSIONS Elderly patients with confirmed COVID-19 were more likely to develop ARDS and cardiac injury than younger patients and were more likely to be admitted to the intensive care unit. In addition to routine monitoring and respiratory support, cardiac monitoring and supportive care should be a focus in elderly patients with COVID-19.


Assuntos
Fatores Etários , Infecções por Coronavirus/epidemiologia , Cardiopatias/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , China/epidemiologia , Terapia Combinada , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Cardiopatias/etiologia , Humanos , Pacientes Internados , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Cuidados Paliativos/estatística & dados numéricos , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
20.
Kidney Blood Press Res ; 45(4): 612-622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32712607

RESUMO

INTRODUCTION: Severe acute respiratory viral infections are frequency accompanied by multiple organ dysfunction, including acute kidney injury (AKI). In December 2019, the coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, Hubei Province, China, and rapidly spread worldwide. While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described. We assessed the incidence and clinical characteristics of AKI in patients with laboratory-confirmed COVID-19 and its effects on clinical outcomes. METHODS: We conducted a multicenter, retrospective, observational study of patients with COVID-19 admitted to two general hospitals in Wuhan from 5 January 2020 to 21 March 2020. Demographic data and information on organ dysfunction were collected daily. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 72 h after admission or after 72 h, respectively. RESULTS: Of the 116 patients, AKI developed in 21 (18.1%) patients. Among them, early and late AKI were found in 13 (11.2%) and 8 (6.9%) patients, respectively. Compared with patients without AKI, patients with AKI had more severe organ dysfunction, as indicated by a higher level of disease severity status, higher sequential organ failure assessment (SOFA) score on admission, an increased prevalence of shock, and a higher level of respiratory support. Patients with AKI had a higher SOFA score on admission (4.5 ± 2.1 vs. 2.8 ± 1.4, OR 1.498, 95% CI 1.047-2.143 ) and greater hospital mortality (57.1% vs. 12.6%, OR 3.998, 95% CI 1.088-14.613) than patients without AKI in both the univariate and multivariate analyses. Patients with late AKI, but not those with early AKI, had a significantly prolonged length of stay (19.6 vs. 9.6 days, p = 0.015). CONCLUSION: Our findings show that admission SOFA score was an independent risk factor for AKI in COVID-19 patients, and patients with AKI had higher in-hospital mortality. Moreover, AKI development after 72 h of admission was related to prolonged hospitalization time.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Lesão Renal Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Progressão da Doença , Feminino , Mortalidade Hospitalar , Hospitais Gerais , Humanos , Incidência , Testes de Função Renal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/terapia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Equilíbrio Hidroeletrolítico
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