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1.
Surg Clin North Am ; 100(4): 695-705, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32681870

RESUMO

Wound healing is affected by several factors. Preexisting diagnoses may significantly alter, delay, or inhibit normal wound healing. This is most commonly seen with chronic disorders, such as diabetes and renal failure, but also occurs secondary to aging and substance abuse. Less commonly, genetic or inflammatory disorders are the cause of delayed wound healing. In some cases, it is not the illness, but the treatment that can inhibit wound healing. This is seen in patients getting chemotherapy, radiation, steroids, methotrexate, and a host of other medications. Understanding these processes may help treat or avoid wound healing problems.


Assuntos
Falência Renal Crônica/fisiopatologia , Cicatrização/fisiologia , Ferimentos e Lesões/fisiopatologia , Fatores Etários , Antineoplásicos/efeitos adversos , Doenças Autoimunes/complicações , Doenças Autoimunes/fisiopatologia , Doença Crônica , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/fisiopatologia , Humanos , Infecções/complicações , Infecções/fisiopatologia , Falência Renal Crônica/complicações , Transtornos Nutricionais/complicações , Transtornos Nutricionais/fisiopatologia , Lesões por Radiação/complicações , Lesões por Radiação/fisiopatologia , Pele/efeitos da radiação , Dermatopatias/complicações , Dermatopatias/fisiopatologia , Fumar/efeitos adversos , Fumar/fisiopatologia , Ferimentos e Lesões/complicações
2.
Cell ; 181(6): 1194-1199, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: covidwho-525968

RESUMO

SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.


Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Predisposição Genética para Doença , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Fatores Etários , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Resistência à Doença , Estudos de Associação Genética , Doenças Genéticas Inatas/imunologia , Variação Genética , Genoma Humano , Interações Hospedeiro-Patógeno , Humanos , Infecções/genética , Infecções/imunologia , Infecções/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia
3.
Cell ; 181(6): 1194-1199, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: covidwho-245693

RESUMO

SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.


Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Predisposição Genética para Doença , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Fatores Etários , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Resistência à Doença , Estudos de Associação Genética , Doenças Genéticas Inatas/imunologia , Variação Genética , Genoma Humano , Interações Hospedeiro-Patógeno , Humanos , Infecções/genética , Infecções/imunologia , Infecções/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia
4.
PLoS One ; 15(5): e0232497, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392257

RESUMO

BACKGROUND: Spleen volume reduction followed by re-expansion has been described in acute ischemic stroke in both animal and human studies. Splenic contraction might be partially due to sympathetic hyperactivity and might be accompanied by release of splenocytes in the peripheral circulation, leading to immunodepression. AIMS: To investigate whether spleen volume changes in the first week after stroke are associated with post-stroke infections, changes in lymphocytes count and autonomic dysfunction. METHODS: In patients with acute ischemic stroke, spleen sizes were calculated from abdominal CT images on day one and day seven. Spleen size reduction was defined as > 10% spleen size reduction between day one and day seven. Post stroke infections were diagnosed during the first seven days after stroke onset using the modified criteria of the US Center of Disease Control and Prevention. We assessed the time course of leukocyte subsets and analysed pulse rate variability (PRV) indices. RESULTS: Post-stroke infections occurred in six out of 11 patients (55%) with spleen size reduction versus in five out of 27 patients (19%) without spleen size reduction (p = 0,047). Spleen size reduction was associated with a drop in lymphocytes and several lymphocyte subsets from admission to day one, and a higher NIHSS at admission and at day three (p = 0,028 and p = 0,006 respectively). No correlations could be found between spleen volume change and PRV parameters. CONCLUSION: Post-stroke infections and a drop in lymphocytes and several lymphocyte subsets are associated with spleen volume reduction in acute ischemic stroke.


Assuntos
Infecções/diagnóstico por imagem , Infecções/etiologia , Baço/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Animais , Sistema Nervoso Autônomo/fisiopatologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Infecções/fisiopatologia , Contagem de Linfócitos , Subpopulações de Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Projetos Piloto , Estudos Prospectivos , Baço/patologia , Acidente Vascular Cerebral/fisiopatologia , Tomografia Computadorizada por Raios X
5.
Cell ; 181(6): 1194-1199, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32405102

RESUMO

SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.


Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Predisposição Genética para Doença , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Fatores Etários , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Resistência à Doença , Estudos de Associação Genética , Doenças Genéticas Inatas/imunologia , Variação Genética , Genoma Humano , Interações Hospedeiro-Patógeno , Humanos , Infecções/genética , Infecções/imunologia , Infecções/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia
6.
Nat Commun ; 10(1): 5563, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804490

RESUMO

The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies. However, whether this mechanism governs native non-transplant B-ALL development is unknown. Here we show that, surprisingly, AID genetic deletion does not affect B-ALL development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. We next test the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. The generation of AID off-target mutagenic activity in precursor B-cells does not promote B-ALL. Likewise, known drivers of human B-ALL are not preferentially targeted by AID. Overall these results suggest that infections promote B-ALL through AID-independent mechanisms, providing evidence for a new model of childhood B-ALL development.


Assuntos
Linfócitos B/metabolismo , Transformação Celular Neoplásica/metabolismo , Citidina Desaminase/metabolismo , Infecções/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Animais , Linfócitos B/patologia , Transformação Celular Neoplásica/genética , Criança , Citidina Desaminase/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Infecções/genética , Estimativa de Kaplan-Meier , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Knockout , Fator de Transcrição PAX5/genética , Fator de Transcrição PAX5/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
7.
Khirurgiia (Mosk) ; (10): 43-49, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31626238

RESUMO

OBJECTIVE: To analyze the effectiveness of complex therapy of necrotizing infection using the original method of stimulation of angiogenesis in patients with chronic arterial insufficiency of the lower extremities. MATERIAL AND METHODS: In 53 patients, operations were performed using the proposed technologies for stimulation of angiogenesis. A control group consisting of 56 patients was formed to compare the results of treatment. They had standard vascular therapy for the correction of ischemia. Morphological studies of the muscles of the lower extremities included assessment of capillary bed density and spatial orientation of the capillaries before and after treatment. Computed angiography of the lower extremities followed by calculation of perfusion index was performed to assess changes in the microvasculature. Clinical evaluation of the results was carried out using R. Rutherford scale. RESULTS: Revascularization resulted significant augmentation of capillary bed density and the number of functioning capillaries in muscular tissue. This was accompanied by increased perfusion index and TcPO2 values. The effect of treatment is observed in 12-14 days after surgery and persists for a long time. The best outcomes are found in patients with ischemia grade IIb-III. Incidence of lower limb amputations was more than 2 times lower in the main group compared with the control group. CONCLUSION: Combined stimulation of angiogenesis including mechanical tunneling of the muscles of the affected limb and administration of platelet rich plasma is effective procedure. This method does not require complex equipment and may be used in the treatment of patients with complications of chronic lower limb ischemia and contraindicated direct arterial reconstruction.


Assuntos
Arteriopatias Oclusivas/cirurgia , Capilares/cirurgia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Necrose/cirurgia , Neovascularização Fisiológica , Arteriopatias Oclusivas/fisiopatologia , Capilares/fisiopatologia , Humanos , Infecções/fisiopatologia , Infecções/terapia , Isquemia/fisiopatologia , Isquemia/cirurgia , Extremidade Inferior/fisiopatologia , Microvasos/fisiopatologia , Microvasos/cirurgia , Músculo Esquelético/fisiopatologia , Músculo Esquelético/cirurgia , Necrose/etiologia , Necrose/fisiopatologia , Plasma Rico em Plaquetas/fisiologia , Resultado do Tratamento
8.
Curr Opin Organ Transplant ; 24(5): 527-534, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31385886

RESUMO

PURPOSE OF REVIEW: Posttransplantation infections are common. It is anticipated that infection will be no less common in xenotransplantation recipients. Prolonged xenograft survivals have resulted from advances in immunosuppressive strategies and development of swine that decrease host immune responses via genetic manipulation, notably CRISPR/cas9 manipulation. As prospects for clinical trials improve, consideration of the unique infectious risks posed by xenotransplantation reemerge. RECENT FINDINGS: Organisms likely to cause infection in human recipients of porcine xenografts are unknown in advance of clinical trials. Microbiological screening of swine intended as xenograft donors can be more intensive than is currently feasible for human allograft donors. Monitoring infection in recipients will also be more intensive. Key opportunities in infectious diseases of xenotransplantation include major technological advances in evaluation of the microbiome by unbiased metagenomic sequencing, assessments of some risks posed by porcine endogenous retroviruses (PERVs) including antiretroviral susceptibilities, availability of swine with deletion of genomic PERVs, and recognition of the rapidly changing epidemiology of infection in swine worldwide. SUMMARY: Unknown infectious risks in xenotransplantation requires application of advanced microbiological techniques to discern and prevent infection in graft recipients. Clinical trials will provide an opportunity to advance the safety of all of organ transplantation.


Assuntos
Sobrevivência de Enxerto/fisiologia , Controle de Infecções/métodos , Infecções/etiologia , Transplante de Órgãos , Transplante Heterólogo , Animais , Humanos , Infecções/fisiopatologia , Técnicas Microbiológicas , Suínos
9.
Ann Acad Med Singapore ; 48(5): 145-149, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31210251

RESUMO

INTRODUCTION: The National Early Warning Score (NEWS) is well established in acute medical units to identify acutely deteriorating patients and is shown to have good prognostic value. NEWS, however, has only been used in the Emergency Department as a triage tool. We aimed to evaluate the validity of NEWS in Acute Medical Ward (AMW) that treats predominantly acute infection-related conditions to the Internal Medicine service. MATERIALS AND METHODS: We undertook a retrospective cohort study and analysed NEWS records of all patients admitted to AMW at Singapore General Hospital between 1 August 2015 and 30 July 2017. The outcome was defined as deterioration that required transfer to Intermediate Care Area (ICA), Intensive Care Unit (ICU) or death within 24 hours of a vital signs observation set. RESULTS: A total of 298,743 vital signs observation sets were obtained from 11,300 patients. Area under receiver operating characteristic curve for any of the 3 outcomes (transfer to ICA, ICU or death) over a 24-hour period was 0.896 (95% confidence interval, 0.890-0.901). Event rate was noted to be high above 0.250 when the score was >9. In the medium-risk group (score of 5 or 6), event rate was <0.125. CONCLUSION: NEWS accurately triages patients according to the likelihood of adverse outcomes in infection-related acute medical settings.


Assuntos
Escore de Alerta Precoce , Unidades Hospitalares/estatística & dados numéricos , Infecções , Medição de Risco/métodos , Sepse/diagnóstico , Triagem , Feminino , Mortalidade Hospitalar , Humanos , Infecções/complicações , Infecções/epidemiologia , Infecções/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/etiologia , Sepse/terapia , Índice de Gravidade de Doença , Singapura/epidemiologia , Triagem/métodos , Triagem/normas
11.
Pancreatology ; 19(5): 638-645, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31204259

RESUMO

BACKGROUND: /Objectives: Evaluation of the local and systemic effects of aging on the severity of acute pancreatitis (AP) in an experimental rat model in elderly animals. METHODS: AP was induced in Wistar rats by intraductal 2.5% taurocholate injection and divided into two groups: Young (3 month old) and Aged (18 month old). Two and 24 h after AP induction blood samples were collected for determinations of amylase, AST, ALT, urea, creatinine, glucose, and of plasma I-FABP. TNF-α and IL-6 levels were determined in serum and ascitic fluid. Liver mitochondrial function and malondialdehyde (MDA) contents, pancreas histological analysis, and pulmonar myeloperoxidade (MPO) activity were performed. Bacterial translocation was evaluated by bacterial cultures of pancreas. RESULTS: A significant increase in serum amylase, AST, ALT, urea, creatinine, glucose, I-FABP, and IL-6 levels, and a reduction in serum and ascitic fluid TNF-α levels were observed in the aged group compared to the young group. Liver mitochondrial dysfunction, MDA contents, and pulmonary MPO activity were increased in the Aged AP group compared to the Young AP group. Positive bacterial cultures obtained from pancreas tissue in aged group were significantly increased compared to the young group. Acinar necrosis was also increased in aged AP group when compared to young AP group. CONCLUSION: Aging worsens the course of acute pancreatitis evidenced by increased local and systemic lesions and increased bacterial translocation.


Assuntos
Envelhecimento/patologia , Pancreatite/patologia , Doença Aguda , Animais , Citocinas/sangue , Proteínas de Ligação a Ácido Graxo/metabolismo , Infecções/complicações , Infecções/fisiopatologia , Peroxidação de Lipídeos , Masculino , Mitocôndrias Hepáticas/metabolismo , Necrose , Oxirredução , Pancreatite/cirurgia , Peroxidase/metabolismo , Fosforilação , Ratos , Ratos Wistar
12.
Horm Behav ; 113: 67-75, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31047886

RESUMO

Pathogen threat affects social preferences and responses across species. Here we examined the effects of social context and the infection status of conspecific females and males on the social and mate responses of female mice. The responses of female mice to males were rapidly affected by the presence of infected female conspecifics and infected males. In mice odor cues drive appetitive and aversive social and mate responses. Brief (1 min) exposure to the fresh urinary odors of females infected with the murine nematode parasite, Heligmosomoides polygyrus, attenuated the responses of other uninfected females to the odors of naturally preferred unfamiliar males and enhanced their preferences for familiar males. Likewise exposure to the odors of a male either infected with H. polygyrus or treated with the bacterial endotoxin, lipopolysaccharide, reduced the responses of females to the odors of unfamiliar males. In addition, females displayed an avoidance of, and discrimination against, male mice whose odors had been associated with that of an infected female ("guilt by association") and a preference for the odors associated with an uninfected female ("mate copying"). These shifts in preferences for female associated male odors were attenuated in a dose-related manner by pre-treatment with the oxytocin receptor antagonist, L-368,899. These findings show that social information associated with the infection status of conspecifics can rapidly bias the mate preferences of female mice in an oxytocin receptor dependent manner.


Assuntos
Sinais (Psicologia) , Infecções/psicologia , Ocitocina/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Animais não Endogâmicos , Comportamento de Escolha/fisiologia , Asco , Feminino , Infecções/fisiopatologia , Masculino , Camundongos , Odorantes , Ocitocina/farmacologia , Receptores de Ocitocina/metabolismo , Receptores de Ocitocina/fisiologia , Comportamento Social , Meio Social
14.
Crit Care ; 23(1): 69, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845977

RESUMO

BACKGROUND: Fever improves pathogen control at a significant metabolic cost. No randomized clinical trials (RCT) have compared fever treatment thresholds in critically ill children. We performed a pilot RCT to determine whether a definitive trial of a permissive approach to fever in comparison to current restrictive practice is feasible in critically ill children with suspected infection. METHODS: An open, parallel-group pilot RCT with embedded mixed methods perspectives study in four UK paediatric intensive care units (PICUs) and associated retrieval services. Participants were emergency PICU admissions aged > 28 days to < 16 years receiving respiratory support and supplemental oxygen. Subjects were randomly assigned to permissive (antipyretic interventions only at ≥ 39.5 °C) or restrictive groups (antipyretic interventions at ≥ 37.5 °C) whilst on respiratory support. Parents were invited to complete a questionnaire or take part in an interview. Focus groups were conducted with staff at each unit. Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between group separation of temperature and safety. RESULTS: One hundred thirty-eight children met eligibility criteria of whom 100 (72%) were randomized (11.1 patients per month per site) without prior consent (RWPC). Consent to continue in the trial was obtained in 87 cases (87%). The mean maximum temperature (95% confidence interval) over the first 48 h was 38.4 °C (38.2-38.6) in the restrictive group and 38.8 °C (38.6-39.1) in the permissive group, a mean difference of 0.5 °C (0.2-0.8). Protocol deviations were observed in 6.8% (99/1438) of 6-h time periods and largely related to patient comfort in the recovery phase. Length of stay, duration of organ support and mortality were similar between groups. No pre-specified serious adverse events occurred. Staff (n = 48) and parents (n = 60) were supportive of the trial, including RWPC. Suggestions were made to only include invasively ventilated children for the duration of intubation. CONCLUSION: Uncertainty around the optimal fever threshold for antipyretic intervention is relevant to many emergency PICU admissions. A more permissive approach was associated with a modest increase in mean maximum temperature. A definitive trial should focus on the most seriously ill cases in whom antipyretics are rarely used for their analgesic effects alone. TRIAL REGISTRATION: ISRCTN16022198 . Registered on 14 August 2017.


Assuntos
Infecções/complicações , Níveis Máximos Permitidos , Resultado do Tratamento , Criança , Pré-Escolar , Estado Terminal/terapia , Feminino , Febre/etiologia , Febre/fisiopatologia , Grupos Focais/métodos , Humanos , Lactente , Infecções/fisiopatologia , Unidades de Terapia Intensiva Pediátrica/organização & administração , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Projetos Piloto , Inquéritos e Questionários , Reino Unido
15.
Intern Emerg Med ; 14(4): 539-548, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30729384

RESUMO

Either hypoglycemia or hypoalbuminemia alone is an independent condition associated with increased risk of mortality in critical illness. This study evaluates whether the mortality risk increases in septic patients if these conditions are combined. Patients admitted to our hospital from 2008 to 2015 who satisfied the definition of sepsis were targeted (n = 336). We classified cases into three groups based on blood glucose (BG) level measured at admission: hypoglycemia (Hypo-G; BG < 80 mg/dl), intermediate glycemia (Inter-G; 80-199 mg/dl), and hyperglycemia (Hyper-G; ≥ 200 mg/dl) group, and then estimated mortality. We also compared the clinical data of these glycemic groups in combination with hypoalbuminemia (Hypo-A) or Inter-G with non-hypoalbuminemia (Inter-G + Nonhypo-A), as a secondary analysis. Diagnostic cut-off level of Hypo-A (< 2.8 mg/dl) was determined using the ROC curve between blood albumin and mortality. In Hypo-G group (n = 40), APACHE II/SOFA scores are significantly higher than in the Inter-G (n = 196) and Hyper-G groups (n = 100). Mortality is 52.5% in the Hypo-G and 60.0% in the Hypo-G with Hypo-A (Hypo-G + Hypo-A) groups. Significantly higher APACHE II or SOFA scores and mortality are observed in the Hypo-G + Hypo-A group compared to the Inter-G + Nonhypo-A group. A higher mortality risk is observed in cases with Hypo-G + Hypo-A (OR 5.065) than those with Hypo-G (OR 3.503), Inter-G (OR 1.175), Hyper-G (OR 1.756) or Hypo-A (OR 3.243), calculated by a single logistic-regression analysis. Hypo-G + Hypo-A in patients with sepsis is related to higher ICU mortality. Physicians should be keenly aware of these conditions to provide immediate intensive treatment after admission of septic patients.


Assuntos
Hipoalbuminemia/etiologia , Hipoglicemia/etiologia , Mortalidade/tendências , Sepse/complicações , APACHE , Idoso , Idoso de 80 Anos ou mais , Feminino , Glucose/análise , Humanos , Hipoalbuminemia/mortalidade , Hipoalbuminemia/fisiopatologia , Hipoglicemia/mortalidade , Hipoglicemia/fisiopatologia , Infecções/complicações , Infecções/epidemiologia , Infecções/fisiopatologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Medição de Risco/métodos , Sepse/mortalidade , Sepse/fisiopatologia
16.
Intern Emerg Med ; 14(4): 603-615, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30725323

RESUMO

Quick Sequential Organ Failure Assessment (qSOFA) was proposed to replace SIRS as a new screening tool for the identification of septic patients at high mortality. However, researches from infected patients outside of ICU especially in Emergency Department (ED) drew contradictory conclusions on the prognostic value of qSOFA. This systematic review evaluated qSOFA as a prognostic marker of infected patients outside of ICU. The primary outcome was hospital mortality or 28- or 30-day mortality. Data were pooled based on sensitivity and specificity. Twenty-four trials with 121,237 participants were included. qSOFA had a poor sensitivity (0.58 [95% CI 0.47-0.67], 0.54 [95% CI 0.43-0.65]) and moderate specificity (0.69 [95% CI 0.48-0.84], 0.77 [95% CI 0.66-0.86]) for prediction of mortality in patients outside of ICU and ED patients only. Studies that used in-hospital mortality showed a higher sensitivity (0.61 [95% CI 0.50-0.71] vs 0.32 [95% CI 0.15-0.49]) and lower specificity (0.70 [95% CI 0.59-0.82] vs 0.92 [95% CI 0.85-0.99]) than studies that used 28 or 30-day mortality. Studies with overall mortality < 10% showed higher specificity (0.89 [95% CI 0.82-0.95] vs 0.62 [95% CI 0.48-0.76]) than studies with overall mortality ≥ 10%. There is no difference in the accuracy of diagnosis of sepsis between positive qSOFA scores and SIRS criteria. qSOFA was poor sensitivity and moderate specificity in predicting mortality of infected patients outside of ICU especially in ED. Combining qSOFA and SIRS may be helpful in predicting mortality.


Assuntos
Infecções/diagnóstico , Escores de Disfunção Orgânica , Prognóstico , Fatores de Tempo , Mortalidade Hospitalar , Humanos , Infecções/fisiopatologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Sensibilidade e Especificidade
18.
Neurol Sci ; 40(5): 915-922, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30604335

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is an encephalopathy characterized by a rapid onset of symptoms including headache, seizures, confusion, blurred vision, and nausea associated with a typical magnetic resonance imaging appearance of reversible subcortical vasogenic edema prominent and not exclusive of parieto-occipital lobes. Vasogenic edema is caused by a blood-brain barrier leak induced by endothelial damage or a severe arterial hypertension exceeding the limits of cerebral blood flow autoregulation. Although the exact pathophysiological mechanism is still unclear, frequent conditions that may induce PRES include severe hypertension, eclampsia/pre-eclampsia, acute kidney diseases and failure, immunosuppressive therapy, solid organ, or bone marrow transplantation. Conversely to other conditions, which may induce PRES, the link between severe infection or sepsis and PRES, often associated with gram-positive bacteria, is still poorly understood and less well known. Clinicians from multiple disciplines, such as neurologists and internists, may encounter during their profession patients with severe infection or sepsis and should consider the possible association between PRES and these conditions. We systematically reviewed the literature about this association in order to provide a helpful clinical insight of such complex pathophysiological mechanism, highlighting the importance of recognizing PRES in such a complex clinical scenario.


Assuntos
Infecções/fisiopatologia , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Humanos
19.
Int J Oncol ; 54(3): 779-796, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628661

RESUMO

Numerous types of cancer have been shown to be associated with either ischemic or hemorrhagic stroke. In this review, the epidemiology and pathophysiology of stroke in cancer patients is discussed, while providing vital information on the diagnosis and management of patients with cancer and stroke. Cancer may mediate stroke pathophysiology either directly or via coagulation disorders that establish a state of hypercoagulation, as well as via infections. Cancer treatment options, such as chemotherapy, radiotherapy and surgery have all been shown to aggravate the risk of stroke as well. The clinical manifestation varies greatly depending upon the underlying cause; however, in general, cancer­associated strokes tend to appear as multifocal in neuroimaging. Furthermore, several serum markers have been identified, such as high D­Dimer levels and fibrin degradation products. Managing cancer patients with stroke is a delicate matter. The cancer should not be considered a contraindication in applying thrombolysis and recombinant tissue plasminogen activator (rTPA) administration, since the risk of hemorrhage in cancer patients has not been reported to be higher than that in the general population. Anticoagulation, on the contrary, should be carefully examined. Clinicians should weigh the benefits and risks of anticoagulation treatment for each patient individually; the new oral anticoagulants appear promising; however, low­molecular­weight heparin remains the first choice. On the whole, stroke is a serious and not a rare complication of malignancy. Clinicians should be adequately trained to handle these patients efficiently.


Assuntos
Neoplasias/complicações , Neoplasias/fisiopatologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Anticoagulantes/uso terapêutico , Biomarcadores/análise , Humanos , Infecções/complicações , Infecções/fisiopatologia , Neoplasias/terapia , Neuroimagem , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Trombofilia/complicações , Trombofilia/fisiopatologia , Ativador de Plasminogênio Tecidual/uso terapêutico
20.
Mol Psychiatry ; 24(6): 869-887, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30116031

RESUMO

Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942-2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.71; 95% CI 0.33-1.09) and affective disorders (4 studies [298 patients]; SMD = 0.41; 95% CI 0.23-0.60, I2 = 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies [97 patients]; SMD = 0.41; 95% CI 0.15-0.67, I2 = 0%) and affective disorders (2 studies [53 patients]; SMD = 0.80; 95% CI 0.39-1.21, I2 = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.68; 95% CI 0.30-1.06), whereas the IgG Albumin ratio was decreased (1 study [32 patients]; SMD = -0.62; 95% CI -1.13 to -0.12). Interleukin-6 (IL-6) levels (7 studies [230 patients]; SMD = 0.55; 95% CI 0.35-0.76; I2 = 1%) and IL-8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17-0.75, I2 = 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2-6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation.


Assuntos
Inflamação/metabolismo , Transtornos do Humor/fisiopatologia , Esquizofrenia/fisiopatologia , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/metabolismo , Feminino , Humanos , Infecções/líquido cefalorraquidiano , Infecções/fisiopatologia , Inflamação/líquido cefalorraquidiano , Masculino , Transtornos do Humor/líquido cefalorraquidiano , Transtornos Psicóticos/líquido cefalorraquidiano , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/líquido cefalorraquidiano
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