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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1844-1847, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018359

RESUMO

Sepsis is life threatening organ dysfunction caused by microcirculatory dysfunction. With progression of sepsis, the patients are likely to develop septic shock which is associated with multi organ dysfunction. To treat sepsis and septic shock, Thrombomodulin alfa (TM alfa) was developed. Direct observation of the microcirculation may provide new and rich information in terms of the effect of TM alfa on sepsis. Thus we conducted rodent experiments in which we observed the microcirculation with a non-contact optical imaging setup and measured lactate value from collected blood. From the acquired motion pictures, we estimated the blood velocity. As a result, from experiments, the sham rats showed no significant change in both lactate value and the blood velocity during the observation. On the other hand, lactate value of the septic model rats increased and the blood velocity of them decreased. Lactate value of the septic model rats treated with TM alfa decreased after showing an increase while the blood velocity of them increased after showing a decrease. These findings suggest that microcirculatory alteration may be a sign of sepsis as well as septic shock progression and that the TM alfa may be effective for the treatment of sepsis and septic shock.


Assuntos
Sepse , Choque Séptico , Animais , Anticoagulantes , Humanos , Microcirculação , Ratos , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Trombomodulina
2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2772-2775, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018581

RESUMO

Usual care regarding vasopressor (VP) initiation is ill-defined. We aimed to further validate a quantitative model for usual care in the Emergency Department (ED) regarding the timing of VP initiation in sepsis. We retrospectively studied a cohort of adult critically-ill ED patients who also received antibiotics in the ED. We applied a multivariable model previously developed from another patient cohort which distinguishes between time points at which patients were or were not subsequently started on a continuous VP infusion. The model has six independently significant predictors (respiratory rate, Glasgow Coma Scale score, systolic blood pressure, SpO2, administered intravenous fluids, and elapsed time). The outcome was initiation of VP infusion, either within the ED or within 6 hours after leaving the ED. We applied the model to all time points, beginning when all model input parameters were first available for a given patient, and ending when either VP were first started, or the patient left the ED. Out of 55,963 adult ED patients during the two-year study interval, we identified 1,629 who met our inclusion criteria. The area under the receiver operating characteristic curve was 0.81 for all patients, and 0.72 for the subset with at least one hypotensive blood pressure measurement. At a model threshold with sensitivity and specificity 0.74 and 0.74, respectively, the median advance detection time was 170.5 minutes (IQR 53 - 363).


Assuntos
Sepse , Adulto , Estudos de Coortes , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Sepse/tratamento farmacológico , Vasoconstritores/uso terapêutico
3.
Am J Chin Med ; 48(6): 1315-1330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907362

RESUMO

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/tratamento farmacológico , Sepse/tratamento farmacológico , Artemisininas/uso terapêutico , Astragalus propinquus , Berberina/uso terapêutico , Betacoronavirus , Estado Terminal , Emodina/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Mucosa Intestinal , Microcirculação , Pandemias , Permeabilidade , Rheum , Salvia miltiorrhiza
4.
Internist (Berl) ; 61(10): 1002-1009, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32865593

RESUMO

Sepsis and septic shock are still associated with a high mortality and morbidity. A decisive factor for improvement of the outcome is the prompt initiation of an effective antibiotic treatment. The early recognition of sepsis within the first hour is here one of the biggest challenges. Effective empirical treatment comprises purposefully selected broad-spectrum antibiotics and also combination treatment or antimycotics in special situations. De-escalation strategies to narrow down or shorten the treatment are safe and can limit the side effects.


Assuntos
Anti-Infecciosos/uso terapêutico , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Humanos , Resultado do Tratamento
5.
N Z Med J ; 133(1520): 35-49, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994592

RESUMO

AIM: Early recognition and timely management, including prompt administration of antibiotics, has been fundamental in improving the mortality related to sepsis. We aimed to study the effect of the Sepsis Pathway Programme, a set of guidelines for sepsis, on the recognition, early investigation and management of septic patients in the emergency department. METHODS: We conducted a comparative prospective cohort study of patients who presented with suspected sepsis pre- and post-implementation of the Sepsis Pathway. Patients where the Sepsis Pathway was used were identified and followed prospectively to analyse outcomes. This group was compared to a pre-intervention control group who were identified retrospectively before the Sepsis Pathway was implemented to determine if there was any difference in outcomes. RESULTS: A total of 109 patients were identified to be septic in the emergency department following the implementation of the Sepsis Pathway. Of these, 52 cases involved the initiation and completion of the Sepsis Pathway. One hundred and fifty-seven cases were identified in the pre-intervention group of which 18 cases were excluded. The time to antibiotic administration decreased from 182 to 75 minutes (p<0.00001). The proportion of cases where antibiotics were given within the hour was higher in the pathway group (36.5% vs 8.6%, OR 6.09, 95% CI 2.69-13.81, p<0.0001). Similarly, the time to lactate measurement decreased from 64 minutes to 54.5 minutes (p=0.0117) and the proportion of cases where lactate was measured improved from 64% to 92.3% (p=0.0005). Blood culture rates improved from 79.1% to 100%. CONCLUSION: The implementation of the Sepsis Pathway improved time taken to perform investigations and manage patients with sepsis. Although it had improved, there was still a delay in recognition of sepsis and initiation of investigations and management, demonstrating that further strategies need to be employed to reduce poor outcomes associated with sepsis. However, it did not affect ICU admissions, length of stay or mortality.


Assuntos
Antibacterianos/uso terapêutico , Serviço Hospitalar de Emergência/organização & administração , Sepse/tratamento farmacológico , Antibacterianos/administração & dosagem , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Ácido Láctico/análise , Tempo de Internação/tendências , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Sepse/diagnóstico , Sepse/mortalidade , Fatores de Tempo
6.
Biomolecules ; 10(8)2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796765

RESUMO

Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab (HAM8101) is a first-in-class humanized monoclonal anti-Adrenomedullin (anti-ADM) antibody, targeting the sepsis- and inflammation-based vascular and capillary leakage. Within a "treatment on a named-patient basis" approach, Adrecizumab was administered to eight extreme-critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). The patients received a single dose of Adrecizumab, which was administered between 1 and 3 days after the initiation of mechanical ventilation. The SOFA (median 12.5) and SAPS-II (median 39) scores clearly documented the population at highest risk. Moreover, six of the patients suffered from acute renal failure, of whom five needed renal replacement therapy. The length of follow-up ranged between 13 and 27 days. Following the Adrecizumab administration, one patient in the low-dose group died at day 4 due to fulminant pulmonary embolism, while four were in stable condition, and three were discharged from the intensive care unit (ICU). Within 12 days, the SOFA score, as well as the disease severity score (range 0-16, mirroring critical resources in the ICU, with higher scores indicating more severe illness), decreased in five out of the seven surviving patients (in all high-dose patients). The PaO2/FiO2 increased within 12 days, while the inflammatory parameters C-reactive protein, procalcitonin, and interleukin-6 decreased. Importantly, the mortality was lower than expected and calculated by the SOFA score. In conclusion, in this preliminary uncontrolled case series of eight shock patients with life-threatening COVID-19 and ARDS, the administration of Adrecizumab was followed by a favorable outcome. Although the non-controlled design and the small sample size preclude any definitive statement about the potential efficacy of Adrecizumab in critically ill COVID-19 patients, the results of this case series are encouraging.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/complicações , Endotélio Vascular/efeitos dos fármacos , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Sepse/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Infecções por Coronavirus/patologia , Estado Terminal , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Sepse/etiologia
7.
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
8.
Internist (Berl) ; 61(10): 997-1001, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32857172

RESUMO

The management of hemodynamic instability in the context of sepsis or septic shock is at the forefront in emergency care as well as in the intensive care unit. Cardiovascular instability has a dramatic impact on the rate of organ complications and mortality from sepsis. According to the guideline for the treatment of sepsis, mean arterial pressure should not fall below 65 mm Hg. Crystalloid balanced fluid and catecholamines are the cornerstones of therapy management for septic cardiovascular instability. In this article, the most important points of what, when and how much regarding circulation therapy are presented and critically discussed.


Assuntos
Catecolaminas/uso terapêutico , Soluções Cristaloides/uso terapêutico , Sepse/tratamento farmacológico , Hidratação , Humanos , Unidades de Terapia Intensiva , Sepse/diagnóstico , Choque Séptico
9.
Medicine (Baltimore) ; 99(29): e21066, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702849

RESUMO

INTRODUCTION: Sepsis is the most common etiology of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Capillary leakage caused by lung endothelial injury is the central cause of ARDS. The results of research in modern medicine in reducing endothelial damage and restoring endothelial functions are limited. In the previous clinical observations, we found that the Fusu mixture not only improves the clinical symptoms but also reduces the leakage of pulmonary capillaries. Therefore, the purpose of this study is to determine the clinical efficacy of the Fusu mixture combined with Western medicine in the treatment of ARDS caused by sepsis and to explore the mechanism of traditional Chinese medicine. METHODS: This is a prospective, single-center, randomized, single-blind, and controlled clinical study involving 620 eligible patients. The patients will be randomly divided into 2 groups: the Western medicine treatment group and the combination of Chinese and Western medicine treatment group. After 14 days of intervention, the clinical efficacy and safety of the Fusu mixture on sepsis-induced ARDS patients will be observed. The primary outcome will be measured as 28-day mortality. The secondary outcome indices include inflammatory markers (CRP, PCT, IL-6, TNF - α), APACHE II score, SOFA score, days without a ventilator, blood gas analysis (Lac, PaO2 / FiO2), intensive care unit hospital stay time, intensive care unit mortality. Simultaneously, the analysis of the exploratory results will be carried out to analyze the possible mechanism of Fusu mixture in the treatment of sepsis-induced ARDS by the high-throughput sequencing and bioinformatics. DISCUSSION: The purpose of this study is to evaluate the clinical efficacy of Fusu mixture in the treatment of sepsis-induced ARDS and explore its possible mechanism of action. If successful, it will provide evidence-based adjuvant therapy for the clinical treatment of ARDS.


Assuntos
Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/etiologia , Sepse/complicações , Adulto , Gasometria , Síndrome de Vazamento Capilar/complicações , Síndrome de Vazamento Capilar/etiologia , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/normas , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Método Simples-Cego , Resultado do Tratamento
10.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32611807

RESUMO

BACKGROUND AND OBJECTIVES: Vancomycin remains one of the most commonly prescribed antibiotics in NICUs despite recommendations to limit its use for known resistant infections. Baseline data revealing substantially higher vancomycin use in our NICU compared to peer institutions informed our quality improvement initiative. Our aim was to reduce the vancomycin prescribing rate in neonates hospitalized in our NICU by 50% within 1 year and sustain for 1 year. METHODS: In the 60-bed level IV NICU of an academic referral center, we used a quality improvement framework to develop key drivers and interventions including (1) physician education with benchmarking antibiotic prescribing rates; (2) pharmacy-initiated 48-hour antibiotic time-outs on rounds; (3) development of clinical pathways to standardize empirical antibiotic choices for early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis; coupled with (4) daily prospective audit with feedback from the antimicrobial stewardship program. RESULTS: We used statistical process u-charts to show vancomycin use declined from 112 to 38 days of therapy per 1000 patient-days. After education, pharmacy-initiated 48-hour time-outs, and development of clinical pathways, vancomycin use declined by 29%, and by an additional 52% after implementation of prospective audit with feedback. Vancomycin-associated acute kidney injury also declined from 1.4 to 0.1 events per 1000 patient-days. CONCLUSIONS: Through a sequential implementation approach of education, standardization of care with clinical pathways, pharmacist-initiated 48-hour time-outs, and prospective audit with feedback, vancomycin days of therapy declined by 66% over a 1-year period and has been sustained for 1 year.


Assuntos
Gestão de Antimicrobianos/estatística & dados numéricos , Prescrição Inadequada/prevenção & controle , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/organização & administração , Brasil , Procedimentos Clínicos , Enterocolite Necrosante/tratamento farmacológico , Hospitais Pediátricos/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Prescrição Inadequada/estatística & dados numéricos , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Serviço de Farmácia Hospitalar/organização & administração , Estudos Prospectivos , Melhoria de Qualidade , Sepse/tratamento farmacológico
11.
S Afr Med J ; 110(2): 123-125, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657682

RESUMO

BACKGROUND: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality. Surgical site infection (SSI) rates are reported to range from 2.5% to 41%. HAI increases the risk of death by 2 - 11%, and three-quarters of these deaths are directly attributable to SSIs. OBJECTIVES: To determine the incidence of HAI and to identify risk factors amenable to modification with a resultant reduction in infection rates. METHODS: An analysis of HAIs was performed between January and April 2018 in the trauma centre surgical wards at Groote Schuur Hospital, Cape Town, South Africa. RESULTS: There were 769 admissions during the study period. Twenty-two patients (0.03%) developed an HAI. The majority were men, and the mean age was 32 years (range 18 - 57). The mean length of hospital stay (LoS) was 9 days, higher than the mean LoS for the hospital of 6 days. Fourteen patients underwent emergency surgery, 3 patients underwent abbreviated damage control surgery, and 9 patients were admitted to the critical care unit. Most patients with nosocomial sepsis were treated with appropriate culture-based antibiotics (82%). Four patients were treated with amoxicillin/clavulanic acid presumptively prior to culture and sensitivity results, after which antibiotic therapy was tailored. All but 1 patient received antibiotics. CONCLUSIONS: A combination of measures is required to prevent trauma-related infections. By determining the incidence of nosocomial infections in our trauma patients, uniform policies to reduce infection rates further could be determined. Our low incidence of infection may be explained by established preventive care bundles already in place.


Assuntos
Antibacterianos/administração & dosagem , Infecção Hospitalar/epidemiologia , Sepse/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Adolescente , Adulto , Infecção Hospitalar/prevenção & controle , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Sepse/tratamento farmacológico , África do Sul/epidemiologia , Centros de Traumatologia , Serviços Urbanos de Saúde , Adulto Jovem
12.
Chin J Traumatol ; 23(4): 190-195, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32690231

RESUMO

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/complicações , Sepse/etiologia , Corticosteroides/uso terapêutico , Glicoproteínas/uso terapêutico , Humanos , Pandemias , Sepse/tratamento farmacológico , Timalfasina/uso terapêutico
13.
Biomed Res Int ; 2020: 1594726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626733

RESUMO

Acute kidney injury (AKI) is a common complication of sepsis and has also been observed in some patients suffering from the new coronavirus pneumonia COVID-19, which is currently a major global concern. Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has a variety of beneficial properties including anti-inflammatory and antioxidative activities. Here, we investigated the possible protective effects of TQ against kidney damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ+CLP. CLP was performed after 2 weeks of TQ gavage. After 48 h, we measured the histopathological alterations in the kidney tissue and the serum levels of creatinine (CRE) and blood urea nitrogen (BUN). We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1ß, and IL-6)-related protein and gene expression levels. Our results demonstrated that TQ inhibited CLP-induced increased serum CRE and BUN levels. It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1ß, and IL-6 induced by CLP. Furthermore, NF-κB protein level was significantly decreased in the TQ+CLP group than in the CLP group. Together, our results indicate that TQ may be a potential therapeutic agent for sepsis-induced AKI.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/etiologia , Benzoquinonas/uso terapêutico , Sepse/complicações , Sepse/tratamento farmacológico , Lesão Renal Aguda/patologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Betacoronavirus , Nitrogênio da Ureia Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Creatinina/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
14.
Medicine (Baltimore) ; 99(27): e19811, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629622

RESUMO

INTRODUCTION: Nosocomial Enterococcus faecium (E faecium) infections are common among immunocompromised patients; however, sepsis caused by E faecium is rarely encountered in the clinical setting. PATIENT CONCERNS: A 69-year-old woman with a previous history of tuberculosis (TB), developed symptoms of recurrent fever, paroxysmal cough, and exertional dyspnea for over 2 months before she presented to the hospital. DIAGNOSIS: The patient was initially misdiagnosed with recurrent TB, and did not respond to anti-TB therapy. Culture results of blood, endotracheal necrotic tissue, and urine confirmed a diagnosis of multifocal E faecium infection. INTERVENTIONS: On definitive diagnosis, the patient received intensive antimicrobial combination treatment with linezolid, teicoplanin, caspofungin, and voriconazole on the basis of antimicrobial susceptibility results. OUTCOMES: After transient improvement, the patient's condition deteriorated due to secondary infections, and the patient died after discharge against medical advice. CONCLUSION: E faecium bacteremia may cause sepsis in immunocompromised patients, and has a high mortality rate. Careful pathogen detection and early initiation of treatment is crucial to good patient outcome.


Assuntos
Enterococcus faecium/isolamento & purificação , Infecções por Bactérias Gram-Positivas/diagnóstico , Sepse/microbiologia , Idoso , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Feminino , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Sepse/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(6): 691-695, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32684214

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Xuebijing injection for treating sepsis by systematic review. METHODS: Randomized controlled trials (RCT) of relevant Xuebijing injection for sepsis were searched in PubMed, Cochrane Library, CNKI, Wanfang database, VIP database from January 2000 to July 2019. Patients in control group were given conventional treatment, while patients in experimental group were treated with Xuebijing injection combined with conventional treatment. The qualities of the included trials were evaluated according to the Cochrane bias risk assessment tool. Meta-analysis of 28-day mortality, acute physiology and chronic health evaluation II (APACHE II), white blood cell count (WBC), C-reactive protein (CRP) and safety for sepsis patients with Xuebijing injection were conducted by RevMan 5.3 software. And the funnel chart was used to evaluate the publication bias of 28-day mortality. RESULTS: Fourteen clinical studies involving 938 patients in total were enrolled, among whom 475 cases in experimental group and 463 cases in control group. Meta-analysis showed that compared with the control group, the 28-day mortality, APACHE II score, WBC and CRP of the experimental group were significantly decreased [28-day mortality: relative risk (RR) = 0.52, 95% confidence interval (95%CI) was 0.40 to 0.67, P < 0.000 01, I2 = 0%; APACHE II score: mean difference (MD) = -5.48, 95%CI was -7.52 to -3.43, P < 0.000 01, I2 = 86%; WBC: MD = -2.26, 95%CI was -3.35 to -1.17, P < 0.000 1, I2 = 87%; CRP: MD = -37.43, 95%CI was -56.70 to -18.16, P = 0.000 1, I2 = 99%]. None of the 14 literatures reported the safety of Xuebijing injection, and there were no reports of participants' withdrawnness in halfway. Funnel chart analysis showed that there was a publication bias among studies with 28-day mortality. CONCLUSIONS: Xuebijing injection can improve the clinical symptoms, significantly reduce the mortality, and has high clinical application value.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Sepse , APACHE , Humanos , Sepse/tratamento farmacológico , Resultado do Tratamento
16.
Life Sci ; 258: 118161, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32730835

RESUMO

AIMS: Tubulointerstitial inflammation is recognized as a key determinant of progressive sepsis-induced acute kidney injury (AKI). Schisantherin A (SchA) has been shown to be capable of regulating inflammatory processes. In the present study, we explored the possibility of SchA in preventing lipopolysaccharide (LPS)-induced kidney inflammation and injury. MATERIALS AND METHODS: AKI was induced by a single intraperitoneal injection of LPS in CD1 mice, administration of SchA was used for treatment. The protective effect of SchA on renal function and inflammation were analyzed respectively; the NRK-52E cell line was employed for the in vitro study and relative molecular mechanism was explored. KEY FINDINGS: Administration with SchA markedly attenuated LPS-induced damage on renal function and histopathological changes of the kidney. Additionally, pretreatment with SchA could inhibit the expression of inflammatory factors in the kidneys. In NRK-52E cells, SchA treatment significantly inhibited LPS-induced NF-κB activation and pro-inflammatory cytokine expression. Moreover, SchA could promote NRF2 pathway activation, and further blockade of NRF2 activation reversed the SchA-induced inhibition of NF-κB activation. SIGNIFICANCE: These presented results indicated that SchA may have great potential for protecting against sepsis-induced AKI.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/etiologia , Anti-Inflamatórios/uso terapêutico , Ciclo-Octanos/uso terapêutico , Dioxóis/uso terapêutico , Lignanas/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Sepse/complicações , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Ratos , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais/efeitos dos fármacos
17.
PLoS One ; 15(7): e0236864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730359

RESUMO

BACKGROUND: Combination therapy in the treatment of sepsis, especially the value of combining a ß-Lactam antibiotic with an aminoglycoside, has been discussed. This retrospective cohort study including patients with sepsis or septic shock aimed to investigate whether one single dose of gentamicin at admittance (SGA) added to ß-Lactam antibiotic could result in a lower risk of mortality than ß-Lactam monotherapy, without exposing the patient to the risk of nephrotoxicity. METHODS AND FINDINGS: All patients with positive blood cultures were evaluated for participation (n = 1318). After retrospective medical chart review, a group of patients with community-acquired sepsis with positive blood cultures who received ß-Lactam antibiotic with or without the addition of SGA (n = 399) were included for the analysis. Mean age was 74.6 yrs. (range 19-98) with 216 (54%) males. Sequential Organ Failure Assessment score (SOFA score) median was 3 (interquartile range [IQR] 2-5) and the median Charlson Comorbidity Index for the whole group was 2 (IQR 1-3). Sixty-seven (67) patients (17%) had septic shock. The 28-day mortality in the combination therapy group was 10% (20 of 197) and in the monotherapy group 22% (45 of 202), adjusted HR 3.5 (95% CI (1.9-6.2), p = < 0.001. No significant difference in incidence of acute kidney injury (AKI) was detected. CONCLUSION: This retrospective observational study including patients with community-acquired sepsis or septic shock and positive blood cultures, who meet Sepsis-3 criteria, shows that the addition of one single dose of gentamicin to ß-lactam treatment at admittance was associated with a decreased risk of mortality and was not associated with AKI. This antibiotic regime may be an alternative to broad-spectrum antibiotic treatment of community-acquired sepsis. Further prospective studies are warranted to confirm these results.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/mortalidade , Bactérias/efeitos dos fármacos , Infecções Comunitárias Adquiridas/mortalidade , Gentamicinas/administração & dosagem , Sepse/mortalidade , beta-Lactamas/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/patologia , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/patologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/patologia , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Escores de Disfunção Orgânica , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/microbiologia , Sepse/patologia
19.
Niger J Clin Pract ; 23(6): 883-886, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525127

RESUMO

A complicated case of female genital mutilation (FGM) type 2b done in late-pregnancy is presented and the interplay of Yoruba and Kwale culture, in this case, is discussed. A Yoruba who grew up among Kwales/Urhobos had FGM at 38 weeks and 4 days gestation (to assure vaginal delivery) and presented with vulvar hematoma, septicemia, obstructed labor, and a distressed fetus. 5 days after FGM procedure, she had an emergency cesarean section (EmCS), repair of FGM site and baby was admitted in special care. There was the obvious synergy of the Yoruba culture of FGM in infancy and Kwale/Urhobo culture of FGM in pregnancy. The patient and her fetus/baby almost became mortalities but for prompt intervention. The role of sociocultural factors in the practice of FGM is recommended to be further investigated as FGM even in educated women and at the dangerous stage of term pregnancy is still prevalent.


Assuntos
Cesárea , Circuncisão Feminina/efeitos adversos , Hematoma/cirurgia , Complicações do Trabalho de Parto/etiologia , Sepse/diagnóstico , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Drenagem , Tratamento de Emergência , Feminino , Gentamicinas/uso terapêutico , Hematoma/reabilitação , Humanos , Metronidazol/uso terapêutico , Gravidez , Resultado da Gravidez , Sepse/tratamento farmacológico , Sepse/microbiologia , Toxoide Tetânico , Resultado do Tratamento , Doenças da Vulva/tratamento farmacológico , Doenças da Vulva/etiologia , Adulto Jovem
20.
PLoS One ; 15(6): e0234039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555710

RESUMO

Sepsis is characterized by organ dysfunction due to a dysregulated immune response to infection. Currently, no effective treatment for sepsis exists. Platelets are recognized as mediators of the immune response and may be a potential therapeutic target for the treatment of sepsis. We previously demonstrated that NLRP3 inflammasome activation in sepsis-induced activated platelets was associated with multi-organ injury in the cecal-ligation puncture (CLP) rat model of sepsis. In this study, we tested the hypothesis that inhibition of NLRP3 would inhibit platelet activation and attenuate multi-organ injury in the CLP rat. CLP (n = 10) or Sham (n = 10) surgery were performed in male and female Sprague-Dawley rats. A subset of CLP rats were treated with MCC950 (50mg/kg/d), a specific NLRP3 inhibitor (CLP+MCC950, n = 10). At 72 hrs. post-CLP, blood and organs were harvested for analysis of platelet activation, NLRP3 activation, inflammation and end organ damage. Platelet activation increased from 8±0.8% in Sham to 16±1% in CLP, and was reduced to 9±1% in CLP+M rats (p<0.05). NLRP3 activation was also increased in platelets of CLP vs Sham. NLRP3 expression was unchanged in kidney and lung after CLP, but Caspase 1 expression and IL-1ß were increased. MCC950 treatment attenuated NLRP3 activation in platelets. Plasma, kidney, and lung levels of NLRP3 inflammasome associated cytokines, IL-1ß and IL-18, were significantly increased in CLP compared to Sham rats. Inhibition of NLRP3 normalized cytokine levels. Glomerular injury, pulmonary edema, and endothelial dysfunction markers were increased in CLP rats vs Sham. MCC950 treatment significantly decreased renal and pulmonary injury and endothelial dysfunction in CLP+M. Our results demonstrate a role for NLRP3 in contributing to platelet activation and multi-organ injury in sepsis.


Assuntos
Ceco/cirurgia , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Ativação Plaquetária/efeitos dos fármacos , Punções/efeitos adversos , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Animais , Caspase 1/metabolismo , Citocinas/metabolismo , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Ligadura/efeitos adversos , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Sepse/metabolismo
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