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1.
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
2.
Cytokine Growth Factor Rev ; 53: 43-52, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32409230

RESUMO

The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Diabetes Mellitus/patologia , Insuficiência de Múltiplos Órgãos/patologia , Neoplasias/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Comorbidade , Humanos , Hidroxicloroquina/uso terapêutico , Hipertensão/patologia , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Pandemias , Peptidil Dipeptidase A/metabolismo
3.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801287

RESUMO

Multiple organ dysfunction syndrome (MODS) caused by the systemic inflammatory response during sepsis is responsible for millions of deaths worldwide each year, and despite broad consensus concerning its pathophysiology, no specific or effective therapies exist. Recent efforts to treat and/or prevent MODS have included a variety of biologics, recombinant proteins targeting various components of the host response to the infection (e.g., inflammation, coagulation, etc.) Improvements in molecular biology and pharmaceutical engineering have enabled a wide range of utility for biologics to target various aspects of the systemic inflammatory response. The majority of clinical trials to date have failed to show clinical benefit, but some have demonstrated promising results in certain patient populations. In this review we summarize the underlying rationale and outcome of major clinical trials where biologics have been tested as a pharmacotherapy for MODS in sepsis. A brief description of the study design and overall outcome for each of the major trials are presented. Emphasis is placed on discussing targets and/or trials where promising results were observed. Post hoc analyses of trials where therapy demonstrated harm or additional risk to certain patient subgroups are highlighted, and details are provided about specific trials where more stringent inclusion/exclusion criteria are warranted.


Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Sepse/tratamento farmacológico , 1-Alquil-2-acetilglicerofosfocolina Esterase/uso terapêutico , Fosfatase Alcalina/uso terapêutico , Coagulação Sanguínea/genética , Coagulação Sanguínea/imunologia , Ensaios Clínicos como Assunto , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação , Insuficiência de Múltiplos Órgãos/genética , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/patologia , Sepse/genética , Sepse/imunologia , Sepse/patologia
4.
Am J Med Sci ; 358(4): 289-293, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31543102

RESUMO

Patients with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia have poor clinical outcomes and high frequency of mortality, especially in patents with postinfluenza infection. Herein, we report a case of community-acquired pneumonia with multiple organ failure in a 51-year-old patient with initial presentation of flu-like symptoms. The influenza rapid test from the specimen of nasopharyngeal swab was positive for type B influenza virus and was confirmed by real-time polymerase chain reaction. Gram stain of bronchoalveolar lavage fluid revealed gram positive cocci in group. Both sputum and blood culture yielded MRSA. We identified the CA-MRSA was staphylococcal cassette chromosome mec type IV strain carried Panton-Valentine leukocidin gene. The patient made a complete recovery following an 8-week treatment course of linezolid and was discharged with independent daily activity. According to our experience, linezolid may be a reasonable treatment choice for CA-MRSA pneumonia due to the virulence of exotoxins.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Pneumonia/tratamento farmacológico , Coinfecção , Hepatite B/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/tratamento farmacológico
5.
J Infect Chemother ; 25(12): 1037-1039, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31151810

RESUMO

Streptococcal toxic shock syndrome (STSS) is a systemic, life-threatening illness usually caused by invasive respiratory tract or skin and soft tissue infections of Streptococcus pyogenes (group A streptococcus, GAS). We report the case of an adult woman with lactational amenorrhea and GAS vulvovaginitis progressing to STSS. She was admitted to our hospital because of fever, lethargy, and a 2-week history of vaginal discharge; she also had hypotension and multiple organ failure. Blood and urine cultures yielded gram-positive cocci and GAS. After 14 days of antimicrobial therapy, she fully recovered without any complications. The vulvovaginitis was most likely the portal of entry for GAS, which is rarely recognized as a causative pathogen of vulvovaginitis. Lactational amenorrhea is thought to be a risk factor for GAS vulvovaginitis. It is important for clinicians to recognize the possibility of GAS vulvovaginitis in breastfeeding women with vaginal symptoms and consider the necessity of prompt antibiotic treatment.


Assuntos
Antibacterianos/uso terapêutico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes/isolamento & purificação , Vulvovaginite/tratamento farmacológico , Adulto , Amenorreia/imunologia , Aleitamento Materno , Quimioterapia Combinada , Feminino , Humanos , Lactação/imunologia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/microbiologia , Fatores de Risco , Choque Séptico/imunologia , Choque Séptico/microbiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/imunologia , Resultado do Tratamento , Vagina/microbiologia , Vulvovaginite/complicações , Vulvovaginite/imunologia , Vulvovaginite/microbiologia
6.
Pract Neurol ; 19(4): 350-351, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30975708

RESUMO

Both multiple system atrophy and Parkinson's disease may present with parkinsonism and autonomic dysfunction. We describe a patient who initially met the diagnostic criteria for multiple system atrophy and had atypical features for Parkinson's disease including blackouts and pyramidal signs. Ultimately, he was found to have three separate diagnoses rather than a single unifying one.


Assuntos
Insuficiência de Múltiplos Órgãos/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Humanos , Levodopa/uso terapêutico , Masculino , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/tratamento farmacológico
7.
Am J Health Syst Pharm ; 76(8): 493-500, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30851043

RESUMO

PURPOSE: The utility of low-dose corticosteroids in septic shock is reviewed. SUMMARY: Low-dose corticosteroids are suggested as treatment for septic shock patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. However, the risks and benefits of corticosteroids are unclear in this patient population. Previous multicenter trials have yielded conflicting results on the survival benefits of corticosteroids. The recently published Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) and Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trials provide valuable but opposing insight into this ongoing debate. Discordant findings related to mortality in these trials are likely related to differences in study design, corticosteroid regimen, and baseline characteristics among enrolled patients. The utility of adding fludrocortisone to hydrocortisone compared with using hydrocortisone alone is unclear. There does not appear to be an advantage to administering corticosteroids as a continuous infusion to reduce the rate of hyperglycemia or providing a taper to prevent rebound hypotension. CONCLUSION: The mortality benefit of corticosteroids appears to be greatest in septic shock patients with high vasopressor requirements, evidence of multiorgan failure, and primary lung infections. Corticosteroids consistently lead to a faster reversal of shock and may shorten the duration of mechanical ventilation. Corticosteroids do not seem to increase the risk of superinfection at low doses but frequently lead to a higher frequency of hyperglycemia. We recommend the administration of corticosteroids to septic shock patients with escalating doses of vasopressors and evidence of multiorgan dysfunction.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Glucocorticoides/administração & dosagem , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Vasoconstritores/administração & dosagem , Insuficiência Adrenal/etiologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Choque Séptico/complicações , Choque Séptico/mortalidade , Resultado do Tratamento
8.
Mil Med ; 184(Suppl 1): 282-290, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901474

RESUMO

OBJECTIVE: Blast injury is associated with multi-organ failure (MOF), causing significant morbidity and mortality in trauma patients. However, the pathogenesis of blast-induced MOF still remains obscure. In this study, we evaluate the pathophysiological changes related to blast-induced MOF in a clinically relevant rat model of blast injury. METHODS: A moderate blast overpressure was applied to induce injury in anesthetized rats. Pathological changes were evaluated by H&E staining. Complement activation, plasminogen, and myeloperoxidase levels were analyzed by complement hemolytic assay (CH50) and/or ELISA in blood samples. RESULTS: Analysis of lung, brain, and liver tissue at 24 hour after blast overpressure revealed severe injuries. The level of complement components C3 and C1q decreased in parallel with the reduction of CH50 level in injured animals at 1, 3, and 6 hours after blast. Consumption of plasminogen was also detected as early as 1 hour post-injury. Myeloperoxidase levels were elevated within 1 hour of blast injury. CONCLUSION: Our data reveal that blast injury triggers the complement and fibrinolytic systems, which likely contribute to blast-induced MOF. Conceivably, therapies that target these systems early may improve clinical outcomes in blast patients.


Assuntos
Traumatismos por Explosões/tratamento farmacológico , Fibrinolíticos/farmacocinética , Insuficiência de Múltiplos Órgãos/etiologia , Animais , Traumatismos por Explosões/complicações , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Fibrinolíticos/sangue , Fibrinolíticos/uso terapêutico , Escala de Gravidade do Ferimento , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Ratos , Ratos Sprague-Dawley/sangue , Estatísticas não Paramétricas
9.
Medicine (Baltimore) ; 98(10): e14532, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30855439

RESUMO

RATIONALE: Idiopathic hypereosinophilic syndrome (IHES) is a rare disease in which patients which present with eosinophilia-associated damage. Previous studies focused on organ damage from increased eosinophilic granulocytosis. We report IHES in a patient who presented with multiple organ damage (MOD). PATIENT CONCERNS: A 52-year-old male presented with MOD, including myocardial damage suggestive of myocardial infarction, cardiac tamponade, respiratory failure, skin damage, and gastrointestinal damage. DIAGNOSES: The absolute eosinophil count was 12,920/mm, much higher than occurs in other diseases associated with eosinophilia (1500/mm), and suggesting a diagnosis of IHES. INTERVENTIONS: Prednisone combined with hydroxyurea. OUTCOMES: At 6 months after completion of drug treatment, the patient had no chest pain or dyspnea, and the results of a blood panel, chest computed tomography, and gastroscopy were normal. LESSONS: MOD is very rare in patients with IHES. Patients receiving prompt diagnosis and treatment have very good prognoses.


Assuntos
Síndrome Hipereosinofílica/diagnóstico , Diagnóstico Diferencial , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/etiologia
10.
Am J Med ; 132(7): 862-868, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30831065

RESUMO

PURPOSE: The objective of this study was to assess whether earlier antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) and evidence of organ dysfunction identified through electronic alerts improves patient mortality. METHODS: This is a retrospective observational cohort study of adult patients admitted across 5 acute-care hospitals. Mortality, Premier CareScienceTM Analytics Expected Mortality Score, and clinical and demographic variables were obtained through the electronic medical record and Premier (Premier Healthcare Solutions, Inc, Charlotte NC) reports. Patients with 2 SIRS criteria and organ dysfunction were identified through an automated alert. Univariate and multivariate logistic regression was performed. RESULTS: Of those with SIRS and organ dysfunction, 8146 patients were identified through the electronic Best Practice Alert (BPA). Overall 30-day mortality rate was 8.7%. There was no significant association between time to antibiotic administration from BPA alert and mortality (P = 0.21) after adjusting for factors that could influence mortality, including age, heart rate, blood pressure, plasma lactate levels, creatinine, bilirubin levels, and the CareScienceTM Predicted Mortality Risk Score. Female gender (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.06-1.63) and facility were also independently associated with mortality. CONCLUSION: The use of alerts in the electronic medical record may misclassify patients with SIRS as having sepsis. Time to antibiotic administration in patients meeting SIRS criteria and evidence of end-organ dysfunction through BPA alerts did not affect 30-day mortality rates across a health system. Patient severity of illness, gender, and facility also independently predicted mortality. There were higher rates of antibiotic use and Clostridioides difficile infection in patients with BPA alerts.


Assuntos
Alarmes Clínicos , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Idoso , Antibacterianos/uso terapêutico , Registros Eletrônicos de Saúde , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/mortalidade , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/mortalidade , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/mortalidade
11.
Braz J Med Biol Res ; 52(3): e7905, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30810621

RESUMO

Dexmedetomidine (DEX), a selective agonist of α2-adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO2) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-ß, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-ß, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-ß, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α2-adrenergic receptors.


Assuntos
Dexmedetomidina/uso terapêutico , Endotoxemia/tratamento farmacológico , Hemorragia/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Ressuscitação , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Endotoxemia/patologia , Hemorragia/patologia , Masculino , Insuficiência de Múltiplos Órgãos/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Receptores Adrenérgicos beta 2/metabolismo , Fatores de Tempo
12.
BMC Infect Dis ; 19(1): 130, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736735

RESUMO

BACKGROUND: Pseudomonas aeruginosa is an unusual pathogen in community-acquired pneumonia, especially in previously healthy adults, but often indicates poor prognosis. CASE PRESENTATION: We report a previously healthy patient who developed severe community-acquired pneumonia (CAP) caused by P. aeruginosa. He deteriorated to septic shock and multiple organ dysfunction syndrome (MODS) quickly, complicated by secondary hematogenous central nervous system (CNS) infection. After 1 month of organ support and antipseudomonal therapy, he had significant symptomatic improvement and was discharged from hospital. During treatment, the pathogen developed resistance to carbapenems quickly and the antibiotic regimen was adjusted accordingly. CONCLUSIONS: According to our case and related literature review, we conclude that more attention should be paid to community-acquired Pseudomonas aeruginosa pneumonia, because of its rapid progression and poor prognosis.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia Associada a Assistência à Saúde/diagnóstico , Insuficiência de Múltiplos Órgãos/diagnóstico , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Infecções Bacterianas do Sistema Nervoso Central/complicações , Infecções Bacterianas do Sistema Nervoso Central/diagnóstico , Infecções Bacterianas do Sistema Nervoso Central/tratamento farmacológico , Infecções Bacterianas do Sistema Nervoso Central/microbiologia , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Pneumonia Associada a Assistência à Saúde/complicações , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Choque Séptico/complicações , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia
13.
J Neurosurg ; 131(6): 1931-1937, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30641838

RESUMO

OBJECTIVE: Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS. METHODS: The authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI. RESULTS: Two hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94-42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)-6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20-1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01-1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24-2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18-19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06-1.40, p = 0.006). CONCLUSIONS: Admission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/diagnóstico , Citocinas/sangue , Escala de Resultado de Glasgow , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Lesões Encefálicas Traumáticas/tratamento farmacológico , Eritropoetina/uso terapêutico , Feminino , Escala de Resultado de Glasgow/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Probabilidade , Adulto Jovem
14.
Am J Med Sci ; 357(1): 67-74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30278875

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of massive, dysregulated cytokine release and secondary multiorgan failure and is associated with high mortality. Primary HLH occurs predominately in infants and young children with a genetic predisposition. Acquired HLH is less well characterized and usually occurs in younger adults in the setting of severe inflammation triggered by infection or malignancy. Little is known about the disease in elderly. We report 3 patients >50 years old who presented with multiorgan failure and shock without an identifiable source and were ultimately diagnosed with acquired HLH. We performed a literature review of HLH in adults >50 years of age and identified an additional 68 cases. Mean age was 62 years, with male predominance. Most cases were triggered by infection (49%) followed by malignancy (27%). Nineteen patients were treated with the HLH-94 protocol, 11 received corticosteroids and the remainder received non-HLH specific interventions. Overall mortality was 62%.


Assuntos
Linfo-Histiocitose Hemofagocítica/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade
15.
BMJ Case Rep ; 11(1)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30567262

RESUMO

Hyperthyroidism is a common metabolic disorder, although its presentation as an endocrine emergency called thyroid storm is rare. Here we review a case of a thyroid storm as the initial presentation of thyrotoxicosis, with multiple organ failure and haemodynamic collapse due to low-output cardiac dysfunction. Quick intervention with aggressive antithyroid therapy, including steroid pulse, and supportive intensive care measures led to an outstanding improvement and full recovery. The present case clearly shows the beneficial impact of initial clinical suspicion resulting in an early diagnosis and intensive therapy. Moreover, it supports the additional role of steroids to aggressive antithyroid strategy in order to control associated deleterious systemic inflammatory reactions.


Assuntos
Antitireóideos/uso terapêutico , Cuidados Críticos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Choque Cardiogênico/tratamento farmacológico , Esteroides/uso terapêutico , Crise Tireóidea/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Resina de Colestiramina/uso terapêutico , Cuidados Críticos/métodos , Frequência Cardíaca , Hemodinâmica , Humanos , Iodetos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Propiltiouracila/uso terapêutico , Choque Cardiogênico/etiologia , Choque Cardiogênico/fisiopatologia , Crise Tireóidea/complicações , Crise Tireóidea/fisiopatologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Perda de Peso
16.
World J Emerg Surg ; 13: 51, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30459824

RESUMO

Background: Post-cardiac arrest syndrome, which has no specific curative treatment, contributes to the high mortality rate of victims who suffer traumatic cardiac arrest (TCA) and initially can be resuscitated. In the present study, we investigated the potential of ulinastatin to mitigate multiple organ injury after resuscitation in a swine TCA model. Methods: Twenty-one male pigs were subjected to hemodynamic shock (40% estimated blood loss in 20 min) followed by cardiac arrest (electrically induced ventricular fibrillation) and respiratory suspension for 5 min, and finally manual resuscitation. At 5 min after resuscitation, pigs were randomized to receive 80,000 U/kg ulinastatin (n = 7) or the same volume of saline (n = 9) in the TCA group. Pigs in the sham group (n = 5) were not exposed to bleeding or cardiac arrest. At baseline and at 1, 3, and 6 h after the return of spontaneous circulation, blood samples were collected and assayed for tumor necrosis factor-alpha, interleukin 6, and other indicators of organ injury. At 24 h after resuscitation, pigs were sacrificed and apoptosis levels were assessed in samples of heart, brain, kidney, and intestine. Results: One pig died in the ulinastatin group and one pig died in the TCA group; the remaining animals were included in the final analysis. TCA and resuscitation caused significant increases in multiple organ function biomarkers in serum, increases in tumor necrosis factor-alpha, and interleukin 6 in serum and increases in the extent of apoptosis in key organs. All these increases were lower in the ulinastatin group. Conclusion: Ulinastatin may attenuate multiple organ injury after TCA, which should be explored in clinical studies.


Assuntos
Glicoproteínas/farmacologia , Parada Cardíaca/fisiopatologia , Interleucina-6/sangue , Insuficiência de Múltiplos Órgãos/prevenção & controle , Choque/fisiopatologia , Inibidores da Tripsina/farmacologia , Fator de Necrose Tumoral alfa/sangue , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Reanimação Cardiopulmonar/efeitos adversos , Modelos Animais de Doenças , Parada Cardíaca/sangue , Hemodinâmica , Masculino , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Choque/sangue , Suínos
17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(9): 848-854, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30309410

RESUMO

OBJECTIVE: To systematical evaluate the effect of Xuebijing injection in the treatment of multiple organ dysfunction syndrome (MODS). METHODS: With the keywords including Xuebijing, multiple organ dysfunction syndrome, multiple organ dysfunction and multiple organ failure, PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP and Wanfang Data from the database start until March 4th, 2018 were searched for relevant randomized controlled trials (RCTs) related to Xuebijing injection combined conventional treatment versus conventional treatment alone for MODS. The control group received conventional western medicine treatment, including etiological treatment, antibiotics, mechanical ventilation, nutritional support, and comprehensive treatment to maintain fluid, electrolyte, acid and alkali balance. The experimental group was given traditional western medicine combined with Xuebijing injection. The observation parameters included 7-day and 28-day mortality, acute physiology and chronic health evaluation II (APACHE II) and Marshall score, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the number of platelets, activated partial thromboplastin time (APTT) and prothrombin time (PT). According to the inclusion and exclusion criteria, two evaluators independently screened the literature, extracted data and evaluated the methodological quality of the included studies. RevMan 5.3 software was used for Meta analysis. Funnel plot was used to analyze publication bias. RESULTS: A total of 35 RCTs and 2 131 patients were enrolled, including 1 076 in the experimental group and 1 055 in the control group. The results of Meta analysis showed that compared with control group, Xuebijing combined conventional treatment was in favor to decrease the mortality of patients with MODS [7-day mortality: odds ratio (OR) = 0.42, 99% confidence interval (99%CI) = 0.26-0.69, P < 0.000 01; 28-day mortality: OR = 0.31, 99%CI = 0.21-0.45, P < 0.000 01], also could obviously reduce critical condition degree of APACHE II score and the organ function of Marshall score [APACHE II: mean difference (MD) = 3.24, 99%CI = 2.00-4.49, P < 0.000 01; Marshall score: MD = 1.95, 99%CI = 0.50-3.40, P = 0.000 5]. Meanwhile, the results of conventional western medicine combined with Xuebijing in the removal of IL-6 and TNF-α, platelets increase and improvement of PT were better than those of conventional western medicine (IL-6: MD = 5.56, 99%CI = 1.44-9.68, P = 0.000 5; TNF-α: MD = 4.97, 99%CI = 3.44-6.50, P < 0.000 01; platelets: MD = -50.79, 99%CI = -74.84 to -26.74, P < 0.000 1; PT: MD = 4.55, 99%CI = 3.96-5.14, P < 0.000 01), however, there was no obvious advantage in improving APTT (MD = 0.96, 99%CI = -5.08-7.00, P = 0.68). The analysis of funnel map showed that the effect points of various studies were mainly centered on the amount of combined effect, and the "inverted funnel" type was generally symmetrical distribution. However, because the number of the included studies was less, the literature bias could not be completely eliminated. CONCLUSIONS: Xuebijing injection may through its strong cytokines clearance, platelet increase and blood coagulation improvement to protect the organ function in patients with MODS, so as to reduce the mortality and improve the prognosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , APACHE , China , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Am J Physiol Gastrointest Liver Physiol ; 315(5): G838-G847, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30138574

RESUMO

This study was conducted to investigate the effect of 4-phenylbutyric acid (4-PBA) on vital organ injury following sodium taurocholate-induced acute pancreatitis (AP) in rats and the pertinent mechanism. The serum biochemical indicators and key inflammatory cytokines, histopathological damage and apoptosis of vital organs in rat AP, were evaluated in the presence or absence of 4-PBA. Moreover, mRNA and protein levels of endoplasmic reticulum stress (ERS) markers were assessed. 4-PBA significantly attenuated the structural and functional damage of vital organs, including serum pancreatic enzymes, hepatic enzymes, creatinine, and urea. The morphological changes and infiltration of neutrophils and macrophages were reduced as well. These effects were accompanied by decreased serum levels of proinflammatory TNF-α and IL-1ß. Furthermore, 4-PBA diminished the expression of ERS markers (glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, protein kinase R-like ER kinase, activated transcription factor 6, and type-1 inositol requiring enzyme) in vital organs of AP rats. 4-PBA also reduced AP-induced apoptosis in lung, liver, and kidney tissues as shown by TUNEL assay. The present study demonstrated that 4-PBA protected pancreas, lung, liver, and kidney from injury in rat AP by regulating ERS and mitigating inflammatory response to restrain cell death and further suggested that 4-PBA may have potential therapeutic implications in the disease. NEW & NOTEWORTHY In this study, we suggest that endoplasmic reticulum stress (ERS) is an important player in the development of acute pancreatitis-induced multiorgan injury, providing additional evidence for the proinflammatory role of ERS. Because 4-phenylbutyric acid has been suggested to inhibit ERS in many pathological conditions, it is possible that this effect can be involved in alleviating inflammatory response and cell death to ameliorate vital organ damage following acute pancreatitis induced by sodium taurocholate in rats.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Pancreatite Necrosante Aguda/tratamento farmacológico , Fenilbutiratos/uso terapêutico , Animais , Apoptose , Interleucina-1beta/sangue , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite Necrosante Aguda/complicações , Fenilbutiratos/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
19.
BMJ Case Rep ; 20182018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082461

RESUMO

A 43-year-old Japanese man with a low haemoglobin level of 1.3 g/dL and multiorgan dysfunction syndrome (MODS) was admitted to our hospital. He was diagnosed with folate deficiency, which was initially attributed to his malnutrition. He was transfused with several units of packed red blood cells and treated with folate, thiamine and vitamin B12 supplements; he showed a prompt haematological response and recovery from MODS. However, 3 weeks after the initial recovery, he had a relapse of pancytopenia and developed high-grade fever along with rapidly enlarging, generalised lymphadenopathy. Bone marrow biopsy revealed hemophagocytosis, and lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified. Folate supplementation may have promoted lymphoma progression.


Assuntos
Deficiência de Ácido Fólico/tratamento farmacológico , Ácido Fólico/efeitos adversos , Linfoma de Células T Periférico/diagnóstico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Progressão da Doença , Evolução Fatal , Humanos , Linfoma de Células T Periférico/sangue , Masculino , Recidiva Local de Neoplasia/sangue
20.
Front Immunol ; 9: 891, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867926

RESUMO

Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr), at a clinically relevant time point in vivo would reduce the severity of organ injury in this model. CONCLUSIONS: We have shown that the release of mtDNA is sufficient for the development of multiple organ injury. MtDNA concentrations likely peak at different points in the early postinjury phase dependent on the degree of isolated trauma vs combined trauma and hemorrhagic shock. HDMBr scavenging of circulating mtDNA (and nuclear DNA, nDNA) is associated with rescue from severe multiple organ injury in the animal model. This suggests that HDMBr could have utility in rescue from human trauma-induced MODS.


Assuntos
DNA Bacteriano/imunologia , DNA Mitocondrial/imunologia , Brometo de Hexadimetrina/uso terapêutico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Traumatismo Múltiplo/tratamento farmacológico , Choque Hemorrágico/tratamento farmacológico , Adulto , Idoso , Alarminas/imunologia , Alarminas/metabolismo , Animais , Estudos de Coortes , DNA Bacteriano/sangue , DNA Mitocondrial/sangue , Modelos Animais de Doenças , Feminino , Brometo de Hexadimetrina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/patologia , Traumatismo Múltiplo/imunologia , Traumatismo Múltiplo/mortalidade , Traumatismo Múltiplo/patologia , Estudos Prospectivos , Ratos Wistar , Choque Hemorrágico/imunologia , Choque Hemorrágico/mortalidade , Choque Hemorrágico/patologia , Índices de Gravidade do Trauma , Resultado do Tratamento , Adulto Jovem
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