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1.
Khirurgiia (Mosk) ; (4): 21-28, 2021.
Artigo em Russo | MEDLINE | ID: mdl-33759464

RESUMO

OBJECTIVE: To determine the main trigger mechanisms of multiple organ failure in acute severe pancreatitis. MATERIAL AND METHODS: An experimental study included 26 dogs with pancreatic necrosis. We assessed homeostasis disorders and functional changes in the pancreas, bowel, liver, kidneys, lungs and heart. Forty-six patients with severe acute pancreatitis were examined. We studied homeostasis disorders and functional state of the organs, endotoxemia, lipid peroxidation, phospholipase activity, coagulation system and hypoxia. RESULTS: Injury of various organs and systems due to systemic inflammatory response at the early stage of disease is an important aspect in progression of acute pancreatitis. Membrane destabilizing phenomena and disturbances in tissue component of coagulation system are the most significant factors. Patients with severe acute pancreatitis had significant changes in homeostasis. We distinguished two subgroups of patients. The course of disease was different. In the first subgroup, changes in homeostatic parameters were 15.4-24.2% less than in the second subgroup. This largely determined treatment outcomes as a whole. In the first subgroup, therapy was effective in most cases, in the second one - less effective that required surgical interventions. In the first subgroup, mortality and hospital-stay were less compared to the second subgroup. CONCLUSION: Oxidative stress, hypoxia, activation of phospholipases, and coagulation abnormalities are important in the development of systemic inflammatory response syndrome following acute pancreatitis. These factors are triggers for a cascade of the same kind of pathophysiological phenomena contributing to multiple organ failure and pancreatitis. In the tissues of various organs, proportional growth of these markers is observed until the 6th day, while in the blood - until the 4th day.


Assuntos
Insuficiência de Múltiplos Órgãos , Pancreatite Necrosante Aguda , Síndrome de Resposta Inflamatória Sistêmica , Animais , Progressão da Doença , Cães , Homeostase , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia
2.
Br J Haematol ; 193(1): 43-51, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538335
3.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462030

RESUMO

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.


Assuntos
Bacillus cereus/genética , Exotoxinas/genética , Doenças Transmitidas por Alimentos/diagnóstico , Acetilcisteína/uso terapêutico , Acidose/fisiopatologia , Acidose/terapia , Adulto , Antiarrítmicos/uso terapêutico , Antibacterianos/uso terapêutico , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Bacillus cereus/isolamento & purificação , Transtornos da Coagulação Sanguínea/fisiopatologia , Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue , Encefalopatias , Terapia de Substituição Renal Contínua , Evolução Fatal , Feminino , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/fisiopatologia , Doenças Transmitidas por Alimentos/terapia , Depuradores de Radicais Livres/uso terapêutico , Humanos , Imunocompetência , Falência Hepática/fisiopatologia , Falência Hepática/terapia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Plasmaferese , Insuficiência Renal/fisiopatologia , Insuficiência Renal/terapia , Rabdomiólise/fisiopatologia , Rabdomiólise/terapia , Sepse/fisiopatologia , Sepse/terapia , Choque/fisiopatologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sequenciamento Completo do Genoma
4.
Swiss Med Wkly ; 151: w20420, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33516166

RESUMO

The authors present the case of a 58-year-old man with the unique combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and, later on, haemophagocytic lymphohistiocytosis admitted to the intensive care unit. During his ICU stay the patient developed a variety of complications including acute respiratory distress syndrome, pulmonary embolism, right heart failure and suspected HLH leading to multiorgan failure and death. Despite the proven diagnosis of haemophagocytic lymphohistiocytosis, the excessively high ferritin levels of the patient did not seem fully explained by this diagnosis. Therefore, the authors want to highlight different causes of hyperferritinaemia in critically ill patients and underline the importance of differential diagnoses when interpreting continuously rising ferritin levels.


Assuntos
Lesão Renal Aguda/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Falência Hepática/fisiopatologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Embolia Pulmonar/fisiopatologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Alanina Transaminase/sangue , /complicações , Creatinina/sangue , Progressão da Doença , Evolução Fatal , Insuficiência Cardíaca/etiologia , Humanos , Falência Hepática/sangue , Falência Hepática/etiologia , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Embolia Pulmonar/etiologia , /fisiopatologia , /terapia
5.
Respir Physiol Neurobiol ; 283: 103548, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956843

RESUMO

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Insuficiência de Múltiplos Órgãos/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/fisiopatologia , Arritmias Cardíacas/imunologia , Arritmias Cardíacas/fisiopatologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/imunologia , Endotélio Vascular/metabolismo , Eritrócitos/metabolismo , Gastroenteropatias/imunologia , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/metabolismo , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Inflamação/imunologia , Rim/metabolismo , Fígado/metabolismo , Hepatopatias/imunologia , Hepatopatias/fisiopatologia , Pulmão/metabolismo , Insuficiência de Múltiplos Órgãos/fisiopatologia , Miocárdio/metabolismo , Pandemias , Pneumonia Viral/fisiopatologia , Tromboembolia/imunologia , Tromboembolia/fisiopatologia , Carga Viral
6.
J Am Heart Assoc ; 9(24): e016850, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33317366

RESUMO

Background The physiologic hallmarks of the Fontan circulation-chronically elevated central venous pressures and low cardiac output-have significant effects not only on cardiovascular status but also impact other organ systems. Exercise capacity is limited in many and declines with age, accelerating in adolescence, but with wide variability. We explore the relationship between exercise performance and end-organ function in outpatient subjects with a Fontan circulation. Methods and Results This is a cross-sectional analysis of subject end-organ characterization from our outpatient Fontan circulation clinic with peak oxygen consumption (peak Vo2) at cardiopulmonary exercise testing as the primary outcome. We perform linear regression to assess associations between clinical characteristics and peak Vo2 as well as the magnitude of the association of clinical characteristics with peak Vo2. Of 265 subjects age 12.8 (9.5-16.4) years, there is a negative correlation between age and peak Vo2 (-0.49, P<0.001). Of those undergoing ramp cycle exercise testing, 34% perform above 80% predicted peak Vo2. Variables positively associated with peak Vo2 and their effect size include vitamin D sufficiency (+3.00, P=0.020) and absolute lymphocyte count (+0.23, P=0.005). Status as overweight/obese (-3.91, P=0.003) and hemoglobin (-0.77, P=0.003) are negatively associated. Neither ventricular morphology, timing of Fontan palliation, nor Fontan circulation type affect peak Vo2. Conclusions Higher peak Vo2 in those with a Fontan circulation is associated with younger age, vitamin D sufficiency, absence of overweight/obese, lower hemoglobin, and a healthier hepatic profile. Whether exercise training or other initiatives can modify organ characteristics in those with a Fontan circulation is worthy of exploration.


Assuntos
Tolerância ao Exercício/fisiologia , Técnica de Fontan/estatística & dados numéricos , Cardiopatias Congênitas/cirurgia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Adolescente , Criança , Estudos Transversais , Teste de Esforço/métodos , Feminino , Técnica de Fontan/efeitos adversos , Hemoglobinas/análise , Humanos , Testes de Função Hepática/estatística & dados numéricos , Testes de Função Hepática/tendências , Masculino , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Consumo de Oxigênio/fisiologia , Estudos Retrospectivos , Vitamina D/análise
7.
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
8.
Nursing ; 50(7): 54-60, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32558792

RESUMO

The prognosis for a patient with multiple organ dysfunction syndrome (MODS)-also known as organ dysfunction or organ failure-is grave, and mortality can be high when three or more organ systems fail. This article reviews ongoing abnormalities of organ-specific parameters and a bedside clinical scoring assessment tool to identify the mortality of MODS, focusing on the management of MODS resulting from cardiogenic shock in ICU patients who require support of failing organs to survive.


Assuntos
Insuficiência de Múltiplos Órgãos/enfermagem , Choque Cardiogênico/enfermagem , Humanos , Unidades de Terapia Intensiva , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Avaliação em Enfermagem , Diagnóstico de Enfermagem , Testes Imediatos , Choque Cardiogênico/complicações
10.
Infection ; 48(5): 779-782, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32418190

RESUMO

At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , RNA Viral/sangue , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/imunologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/virologia , Convalescença , Infecções por Coronavirus/virologia , Estado Terminal , Darunavir/administração & dosagem , Darunavir/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Evolução Fatal , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/virologia , Pandemias , Pneumonia Viral/virologia , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatologia , Torsades de Pointes/virologia
11.
Lancet Diabetes Endocrinol ; 8(6): 546-550, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32334646

RESUMO

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Pandemias , Pneumonia Viral/fisiopatologia , Comorbidade , Contraindicações de Medicamentos , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Hipoglicemiantes/administração & dosagem , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Insuficiência de Múltiplos Órgãos/fisiopatologia , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , /fisiopatologia
13.
Mil Med ; 185(Suppl 1): 57-66, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32074309

RESUMO

INTRODUCTION: Rapid aeromedical evacuation (AE) is standard of care in current conflicts. However, not much is known about possible effects of hypobaric conditions. We investigated possible effects of hypobaria on organ damage in a swine model of acute lung injury. METHODS: Lung injury was induced in anesthetized swine via intravenous oleic acid infusion. After a stabilization phase, animals were subjected to a 4 hour simulated AE at 8000 feet (HYPO). Control animals were kept at normobaria. After euthanasia and necropsy, organ damage was assessed by combined scores for hemorrhage, inflammation, edema, necrosis, and microatelectasis. RESULTS: Hemodynamic, neurological, or hematologic measurements were similar prior to transport. Hemodynamic instability became apparent during the last 2 hours of transport in the HYPO group. Histological injury scores in the HYPO group were higher for all organs (lung, kidney, liver, pancreas, and adrenal glands) except the brain, with the largest difference in the lungs (P < 0.001). CONCLUSIONS: Swine with mild acute lung injury subjected to a 4 hour simulated AE showed more injury to most organs and, in particular, to the lungs compared with ground transport. This may exacerbate otherwise subclinical pathology and, eventually, manifest as abnormalities in gas exchange or possibly end-organ function.


Assuntos
Lesão Pulmonar Aguda/etiologia , Insuficiência de Múltiplos Órgãos/patologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Medicina Aeroespacial/métodos , Animais , Modelos Animais de Doenças , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Ácido Oleico/efeitos adversos , Ácido Oleico/farmacologia , Suínos/lesões , Suínos/fisiologia
14.
J Clin Oncol ; 38(1): 29-42, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622133

RESUMO

PURPOSE: Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality. METHODS: Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality. RESULTS: Survivors (mean age ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min; P for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance. CONCLUSION: Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Tolerância ao Exercício/fisiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Neoplasias/mortalidade , Neoplasias/fisiopatologia , Adulto , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Teste de Esforço , Feminino , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/epidemiologia , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Consumo de Oxigênio/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Surg Infect (Larchmt) ; 21(1): 69-74, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31460841

RESUMO

Background: The grading systems for intra-abdominal sepsis (IAS) are not employed commonly in clinical practice because they are too complicated or too specific. We propose to grade IAS with a simple grading system: the TNM system, which is an acronym borrowed from cancer staging, where T indicates Temperature, N indicates Neutrophils, and M indicates Multiple organ failure (MOF). The aim of this prospective observational study is to assess the predictive value of the TNM score on deaths of patients with complicated IAS. Patients and Methods: We considered 147 patients with complicated IAS. Three classes of attribute were chosen: Temperature (T), Neutrophil count (N), and MOF (M). After defining the categories T (T0-T4), N (N0-N3), and M (M0-M2), they were grouped in stages (0-IV). We analyzed specific variables for their possible relation to death: Age, gender, blood transfusion, causes of IAS, T, N, pre-operative organ failure, immunocompromised status, stage 0, I, II, III, and IV. Odds ratios were calculated in a uni-variable and multi-variable analysis. Results: This was the distribution in classes, based on TNM stages: One patient was in stage 0; 15 patients in stage I; 47 patients in stage II; 56 patients in stage III; 28 patients in stage IV. Death occurred in 45 (30.6%) patients. The N, pre-operative organ failure, immunocompromised status, stage III-IV were potential predictors of post-operative death in uni-variable analysis. Only pre-operative organ failure and stage IV were significant independent predictors of post-operative death in multi-variable analysis. Conclusions: The TNM classification is an easy system that could be considered to define the death risk of patients with IAS and to compare patients with sepsis.


Assuntos
Temperatura Corporal , Classificação , Infecções Intra-Abdominais/classificação , Infecções Intra-Abdominais/diagnóstico , Insuficiência de Múltiplos Órgãos/classificação , Insuficiência de Múltiplos Órgãos/diagnóstico , Neutrófilos/classificação , Sepse/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infecções Intra-Abdominais/complicações , Infecções Intra-Abdominais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Razão de Chances , Estudos Prospectivos , Estudos Retrospectivos , Sepse/fisiopatologia , Adulto Jovem
16.
Pediatr Crit Care Med ; 20(12): 1147-1156, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31688812

RESUMO

OBJECTIVES: Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. DESIGN: Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. SETTING: Thirty-five PICUs. PATIENTS: Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. INTERVENTIONS: Randomization to a lower versus higher glucose target group. MEASUREMENTS AND MAIN RESULTS: Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dys function syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). CONCLUSIONS: Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research.


Assuntos
Hiperglicemia/epidemiologia , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Adolescente , Glicemia , Criança , Pré-Escolar , Estado Terminal , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Lactente , Insulina/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Masculino , Fatores de Risco
17.
Pediatr Crit Care Med ; 20(12): 1137-1146, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31568246

RESUMO

OBJECTIVES: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis. DESIGN: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure. SETTING: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: Children with severe sepsis and indwelling arterial or central venous catheters. INTERVENTIONS: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge. MEASUREMENTS AND MAIN RESULTS: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08). CONCLUSIONS: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.


Assuntos
Inflamação/etiologia , Inflamação/fisiopatologia , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Sepse/complicações , Adolescente , Cateteres de Demora , Criança , Pré-Escolar , Cuidados Críticos , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Falência Hepática/etiologia , Masculino , Paralisia/etiologia , Fenótipo , Estudos Prospectivos , Sepse/fisiopatologia , Trombocitopenia/etiologia
18.
Br J Hosp Med (Lond) ; 80(10): 589-593, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31589506

RESUMO

Multiple organ dysfunction and resultant mortality in critically ill patients has been linked with impaired cellular energy supply and oxidative stress. Clinical studies supplementing selenium, on the basis of its role as a key cofactor of antioxidant enzymes, have reported variable outcomes in critically ill patients. However, the synergistic interaction between selenium and coenzyme Q10, which has essential roles in cellular energy supply and as an antioxidant, has not been considered in such studies. This article reviews the link between selenium and coenzyme Q10, and the potential role of their co-supplementation in critical illness.


Assuntos
Estado Terminal/terapia , Suplementos Nutricionais , Insuficiência de Múltiplos Órgãos/prevenção & controle , Selênio/uso terapêutico , Ubiquinona/análogos & derivados , Antioxidantes/farmacologia , Biomarcadores , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Humanos , Mediadores da Inflamação/metabolismo , Insuficiência de Múltiplos Órgãos/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Selênio/administração & dosagem , Ubiquinona/administração & dosagem , Ubiquinona/uso terapêutico
19.
Ann Surg ; 270(3): 502-510, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31356275

RESUMO

OBJECTIVE: We sought to compare traditional inpatient outcomes to long-term functional outcomes and mortality of surgical intensive care unit (SICU) patients with sepsis. SUMMARY OF BACKGROUND DATA: As inpatient sepsis mortality declines, an increasing number of initial sepsis survivors now progress into a state of chronic critical illness (CCI) and their post-discharge outcomes are unclear. METHODS: We performed a prospective, longitudinal cohort study of SICU patients with sepsis. RESULTS: Among this recent cohort of 301 septic SICU patients, 30-day mortality was 9.6%. Only 13 (4%) patients died within 14 days, primarily of refractory multiple organ failure (62%). The majority (n = 189, 63%) exhibited a rapid recovery (RAP), whereas 99 (33%) developed CCI. CCI patients were older, with greater comorbidities, and more severe and persistent organ dysfunction than RAP patients (all P < 0.01). At 12 months, overall cohort performance status was persistently worse than presepsis baseline (WHO/Zubrod score 1.4 ±â€Š0.08 vs 2.2 ±â€Š0.23, P > 0.0001) and mortality was 20.9%. Of note at 12 months, the CCI cohort had persistent severely impaired performance status and a much higher mortality (41.4%) than those with RAP (4.8%) after controlling for age and comorbidity burden (Cox hazard ratio 1.27; 95% confidence interval, 1.14-1.41, P < 0.0001). Among CCI patients, independent risk factors for death by 12 months included severity of comorbidities and persistent organ dysfunction (sequential organ failure assessment ≥6) at day 14 after sepsis onset. CONCLUSIONS: There is discordance between low inpatient mortality and poor long-term outcomes after surgical sepsis, especially among older adults, increasing comorbidity burden and patients that develop CCI. This represents important information when discussing expected outcomes of surgical patients who experience a complicated clinical course owing to sepsis.


Assuntos
Estado Terminal/mortalidade , Mortalidade Hospitalar , Insuficiência de Múltiplos Órgãos/mortalidade , Complicações Pós-Operatórias/mortalidade , Sepse/epidemiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Idoso , Causas de Morte , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Alta do Paciente , Complicações Pós-Operatórias/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Sepse/fisiopatologia , Procedimentos Cirúrgicos Operatórios/métodos , Análise de Sobrevida , Fatores de Tempo
20.
Pediatr Crit Care Med ; 20(7): e311-e318, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31149968

RESUMO

OBJECTIVES: To assess the etiologies and outcomes of patients with secondary hemophagocytic lymphohistiocytosis in the PICU. DESIGN: Prospective observational cohort study. SETTING: A single PICU at a pediatric tertiary hospital in Hanoi, Vietnam. PATIENTS: Pediatric patients meeting the criteria for secondary hemophagocytic lymphohistiocytosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between June 2017 and May 2018, 25 consecutive patients with a mean (SD) age of 23.3 months (21.6 mo) were included. Collected variables included etiologies of hemophagocytic lymphohistiocytosis and clinical and laboratory findings at admission. The Pediatric Index of Mortality 2 score at admission was calculated. Outcomes were death and multiple organ dysfunction. The severity of multiple organ dysfunction was assessed by the Pediatric Logistic Organ Dysfunction 2 score. The mean (SD) Pediatric Index of Mortality 2 predicted mortality rate was 5.6% (7.6%). Cytomegalovirus and Epstein-Barr virus coinfections (60%) were the most common suspected etiology of hemophagocytic lymphohistiocytosis. Other etiologies included Epstein-Barr virus sole infections (20%), cytomegalovirus sole infections (16%), and one unknown cause (4%). Multiple organ dysfunction (excluding hematologic failure) was found in 22 patients (88%) with death occurring in 14 patients (56%). The mean (SD) Pediatric Logistic Organ Dysfunction 2 predicted mortality rate among patients with multiple organ dysfunction was 11.9% (11.2%). Despite having lower Pediatric Index of Mortality 2 predicted mortality rates at admission, Epstein-Barr virus-cytomegalovirus coinfection cases with multiple organ dysfunction had slightly greater Pediatric Logistic Organ Dysfunction 2 predicted mortality rates than Epstein-Barr virus sole infection cases with multiple organ dysfunction: 12.2% (10.5%) versus 11.3% (11.0%). However, these rates were lower than cytomegalovirus sole infection cases with multiple organ dysfunction (14.4% [16.3%]). Area under the curve values for Pediatric Index of Mortality 2 and Pediatric Logistic Organ Dysfunction 2 were 0.74 (95% CI, 0.52-0.95) and 0.78 (95% CI, 0.52-1.00), respectively, suggesting that both scales were fair to good at predicting mortality. CONCLUSIONS: Viral infections, particularly Epstein-Barr virus-cytomegalovirus coinfections, were a common cause of secondary hemophagocytic lymphohistiocytosis. The implication of these coinfections on the clinical course of hemophagocytic lymphohistiocytosis needs to be delineated.


Assuntos
Coinfecção/complicações , Infecções por Citomegalovirus/complicações , Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/virologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/virologia , Criança , Pré-Escolar , Coinfecção/mortalidade , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Insuficiência de Múltiplos Órgãos/fisiopatologia , Escores de Disfunção Orgânica , Taxa de Sobrevida , Centros de Atenção Terciária , Vietnã/epidemiologia
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