Relationship between peripheral ischemic microvascular reserve, persistent hyperlactatemia, and its temporal dynamics in sepsis: a post hoc study.

OBJECTIVE: To measure the prognostic value of peripheral ischemic microvascular reserve in the context of persistent sepsis-induced hyperlactatemia and measure its influence on the temporal dynamics of lactate and the strength of association between these variables. METHODS: This post hoc analysis of the peripheral perfusion index/postocclusive reactive hyperemia trial, an observational cohort study that enrolled patients with sepsis who persisted with lactate levels ≥ 2mmol/L after fluid resuscitation (with or without shock). Peripheral ischemic microvascular reserve was evaluated using the association of the peripheral perfusion index and postocclusive reactive hyperemia techniques. The cutoff point of ∆ peripheral perfusion index peak values (%) defined the groups with low (≤ 62%) and high peripheral ischemic microvascular reserve (> 62%). RESULTS: A total of 108 consecutive patients with persistent sepsis-induced hyperlactatemia were studied. The high peripheral ischemic microvascular reserve group showed higher 28-day mortality than the low peripheral ischemic microvascular reserve group (p < 0.01). The temporal dynamics of lactate within the first 48 hours showed a rapid decrease in lactate levels in the low peripheral ischemic microvascular reserve group (p < 0.01). However, this result was not reproduced in the linear mixed effects model. A weak correlation between peripheral ischemic microvascular reserve (%) and lactate level (mmol/L) was observed within the first 24 hours (r = 0.23; p < 0.05). CONCLUSION: The prognostic value of high peripheral ischemic microvascular reserve was confirmed in the context of persistent sepsis-induced hyperlactatemia. Although there was a weak positive correlation between peripheral ischemic microvascular reserve value and lactate level within the first 24 hours of sepsis diagnosis, the low peripheral ischemic microvascular reserve group appeared to have a faster decrease in lactate over the 48 hours of follow-up.

Peripheral ischemic reserve in sepsis and septic shock as a new bedside prognostic enrichment tool: A Brazilian cohort study.

Microvascular dysfunctions are associated with poor prognosis in sepsis. However, the potential role of clinical assessment of peripheral ischemic microvascular reserve (PIMR), a parameter that characterizes the variation of peripheral perfusion index (PPI) after brief ischemia of the upper arm, as a tool to detect sepsis-induced microvascular dysfunction and for prognostic enrichment has not been established. To address this gap, this study investigated the association of high PIMR with mortality over time in patients with sepsis and its subgroups (with and without shock) and peripheral perfusion (capillary-refill time). This observational cohort study enrolled consecutive septic patients in four Intensive-care units. After fluid resuscitation, PIMR was evaluated using the oximetry-derived PPI and post-occlusive reactive hyperemia for two consecutive days in septic patients. Two hundred and twenty-six patients were included-117 (52%) in the low PIMR group and 109 (48%) in the high PIMR group. The study revealed differences in mortality between groups on the first day, which was higher in the high PIMR group (RR 1.25; 95% CI 1.00-1.55; p = 0.04) and maintained its prognostic significance after multivariate adjustment. Subsequently, this analysis was made for sepsis subgroups and showed significant differences in mortality only for the septic-shock subgroup, with was higher in the high PIMR group (RR 2.14; 95% CI 1.49-3.08; p = 0.01). The temporal ΔPPI peak values (%) analyses did not demonstrate maintenance of the predictive value over the first 48 h in either group (p > 0.05). A moderate positive correlation (r = 0.41) between ΔPPI peak (%) and capillary-refill time (s) was found within the first 24 hours of diagnosis (p < 0.001). In conclusion, detecting a high PIMR within 24 h appears to be a prognostic marker for mortality in sepsis. Furthermore, its potential as a prognostic enrichment tool seems to occur mainly in septic shock.

The effects of flavonoids in experimental sepsis: A systematic review and meta-analysis.

Sepsis is a host's dysregulated immune response to an infection associated with systemic inflammation and excessive oxidative stress, which can cause multiple organ failure and death. The literature suggests that flavonoids, a broad class of secondary plant metabolites, have numerous biological activities which can be valuable in the treatment of sepsis. This study aimed to review the effects of flavonoids on experimental sepsis, focusing mainly on survival rate, and also summarizing information on its mechanisms of action. We searched in the main databases up to November 2022 using relevant keywords, and data were extracted and analyzed qualitatively and quantitatively. Thirty-two articles met the study criteria for review and 29 for meta-analysis. Overall, 30 different flavonoids were used in the studies. The flavonoids were able to strongly inhibit inflammatory response by reducing the levels of important pro-inflammatory mediators, for example, tumor necrosis factor-alpha and interleukin-1ß, oxidative stress, and showed antibacterial and anti-apoptotic actions. The meta-analysis found an increase of 50% in survival rate of the animals treated with flavonoids. They appear to act as multi-target drugs and may be an excellent therapeutic alternative to reduce a number of the complications caused by sepsis, and consequently, to improve survival rate.

Development and psychometric properties of the Cognitive Distortions Questionnaire for Adolescents (CD-Quest-T).

INTRODUCTION: The Cognitive Distortions Questionnaire (CD-Quest) is an instrument that identifies logical errors or cognitive distortions and is used in trial-based cognitive therapy (TBCT). However, it had previously only been available for adults. OBJECTIVES: To develop and validate a version of the CD-Quest for teens (CD-Quest-T) aged 11 to 17 years and test its psychometric properties. METHOD: A total of 299 schoolchildren participated in the investigation. After content validity was assessed, the language was adapted for the target age group, and the length of the instrument was reduced to eight items (from the initial 15). Five cognitive therapists analyzed the content and structure of the items. Finally, to investigate the construct validity of the CD-Quest-T, the instrument was divided into a full scale and two subscales, which measure the frequency of the distortions and the intensity attributed to them, respectively. RESULTS: The overall internal consistency of the scale was α = 0.77, whereas subscale indices were α = 0.75 for the frequency scale and α = 0.73 for the intensity scale. Results from exploratory factor analysis and concurrent validity analysis indicated that the CD-Quest-T items have good psychometric properties and generate scores reliably. CONCLUSION: The psychometric properties of the CD-Quest-T demonstrate its adequacy for measurement of cognitive distortions in adolescents.

Development and psychometric properties of the Cognitive Distortions Questionnaire for Adolescents (CD-Quest-T)

Abstract Introduction The Cognitive Distortions Questionnaire (CD-Quest) is an instrument that identifies logical errors or cognitive distortions and is used in trial-based cognitive therapy (TBCT). However, it had previously only been available for adults. Objectives To develop and validate a version of the CD-Quest for teens (CD-Quest-T) aged 11 to 17 years and test its psychometric properties. Method A total of 299 schoolchildren participated in the investigation. After content validity was assessed, the language was adapted for the target age group, and the length of the instrument was reduced to eight items (from the initial 15). Five cognitive therapists analyzed the content and structure of the items. Finally, to investigate the construct validity of the CD-Quest-T, the instrument was divided into a full scale and two subscales, which measure the frequency of the distortions and the intensity attributed to them, respectively. Results The overall internal consistency of the scale was α = 0.77, whereas subscale indices were α = 0.75 for the frequency scale and α = 0.73 for the intensity scale. Results from exploratory factor analysis and concurrent validity analysis indicated that the CD-Quest-T items have good psychometric properties and generate scores reliably. Conclusion The psychometric properties of the CD-Quest-T demonstrate its adequacy for measurement of cognitive distortions in adolescents.

Relationship between peripheral ischemic microvascular reserve, persistent hyperlactatemia, and its temporal dynamics in sepsis: a post hoc study / Relação entre reserva microvascular isquêmica periférica, hiperlactatemia persistente e sua dinâmica temporal na sepse: um estudo post hoc

ABSTRACT Objective: To measure the prognostic value of peripheral ischemic microvascular reserve in the context of persistent sepsis-induced hyperlactatemia and measure its influence on the temporal dynamics of lactate and the strength of association between these variables. Methods: This post hoc analysis of the peripheral perfusion index/postocclusive reactive hyperemia trial, an observational cohort study that enrolled patients with sepsis who persisted with lactate levels ≥ 2mmol/L after fluid resuscitation (with or without shock). Peripheral ischemic microvascular reserve was evaluated using the association of the peripheral perfusion index and postocclusive reactive hyperemia techniques. The cutoff point of ∆ peripheral perfusion index peak values (%) defined the groups with low (≤ 62%) and high peripheral ischemic microvascular reserve (> 62%). Results: A total of 108 consecutive patients with persistent sepsis-induced hyperlactatemia were studied. The high peripheral ischemic microvascular reserve group showed higher 28-day mortality than the low peripheral ischemic microvascular reserve group (p < 0.01). The temporal dynamics of lactate within the first 48 hours showed a rapid decrease in lactate levels in the low peripheral ischemic microvascular reserve group (p < 0.01). However, this result was not reproduced in the linear mixed effects model. A weak correlation between peripheral ischemic microvascular reserve (%) and lactate level (mmol/L) was observed within the first 24 hours (r = 0.23; p < 0.05). Conclusion: The prognostic value of high peripheral ischemic microvascular reserve was confirmed in the context of persistent sepsis-induced hyperlactatemia. Although there was a weak positive correlation between peripheral ischemic microvascular reserve value and lactate level within the first 24 hours of sepsis diagnosis, the low peripheral ischemic microvascular reserve group appeared to have a faster decrease in lactate over the 48 hours of follow-up.

RESUMO Objetivo: Avaliar o valor prognóstico da reserva microvascular isquêmica periférica no contexto da hiperlactatemia persistente induzida pela sepse, determinar sua influência na dinâmica temporal de lactato e analisar a força da associação entre essas variáveis. Métodos: Análise post hoc do estudo de índice de perfusão periférica/hiperemia reativa pós-oclusiva caracterizada por uma coorte observacional que incluiu pacientes com sepse que persistiram com níveis de lactato ≥ 2mmol/L após a ressuscitação volêmica (com ou sem choque). A reserva microvascular isquêmica periférica foi mensurada utilizando-se a associação dos métodos do índice de perfusão periférica e hiperemia reativa pós-oclusiva. O ponto de corte dos valores da ∆ índice de perfusão periférica de pico (%) definiu os grupos com baixa (≤ 62%) e alta (> 62%) reserva microvascular isquêmica periférica. Resultados: Estudaram-se 108 pacientes consecutivos com hiperlactatemia persistente induzida pela sepse. O grupo com alta reserva microvascular isquêmica periférica apresentou maior mortalidade aos 28 dias em relação ao grupo com baixa reserva microvascular isquêmica periférica (p < 0,01). A dinâmica temporal de lactato nas primeiras 48 horas mostrou redução rápida dos níveis de lactato no grupo com baixa reserva microvascular isquêmica periférica (p < 0,01). No entanto, esse resultado não foi reproduzido no modelo de efeitos mistos lineares. Observou-se fraca correlação (%) entre os valores da reserva microvascular isquêmica periférica e níveis de lactato (mmol/L) nas primeiras 24 horas (r = 0,23; p < 0,05). Conclusão: O valor prognóstico da alta reserva microvascular isquêmica periférica foi confirmado no contexto da hiperlactatemia persistente induzida por sepse. Embora tenha sido observada uma baixa correlação positiva entre os valores da reserva microvascular isquêmica periférica e os níveis de lactato nas primeiras 24 horas do diagnóstico de sepse, o grupo com baixa reserva microvascular isquêmica periférica pareceu apresentar redução mais rápida do lactato nas 48 horas de seguimento.

The prognostic value of peripheral ischemic microvascular reserve in sepsis is not related to calcitonin gene-related peptide or substance P. / O valor prognóstico da reserva microvascular isquêmica periférica na sepse não está vinculado ao peptídeo relacionado ao gene da calcitonina ou à substância P.

OBJECTIVE: To evaluate the mechanisms attributed to the prognostic value of peripheral ischemic microvascular reserve in patients with sepsis. METHODS: This observational cohort study enrolled 46 consecutive septic patients in the intensive care unit between November 2020 and October 2021. After fluid resuscitation, the peripheral ischemic microvascular reserve was evaluated using the association of postocclusion reactive hyperemia with the peripheral perfusion index. Additionally, peripheral venous blood samples were used to evaluate the neuropeptide calcitonin gene-related peptide and substance P levels in the upper limb before and immediately after postocclusion reactive hyperemia. RESULTS: There was no statistically significant correlation (p > 0.05) between basal values (pg/mL) or variations from neuropeptide levels (%) and the peripheral ischemic microvascular reserve (%). CONCLUSION: Although calcitonin gene-related peptide and substance P may have a prognostic role in sepsis, these neuropeptides do not appear to contribute to peripheral ischemic microvascular reserve.

OBJETIVO: Avaliar possíveis mecanismos atribuídos ao valor prognóstico da reserva microvascular isquêmica periférica em pacientes com sepse. MÉTODOS: Este estudo de coorte observacional incluiu 46 pacientes consecutivos com sepse em uma unidade de terapia intensiva entre novembro de 2020 e outubro de 2021. Após a ressuscitação volêmica com fluidos, avaliou-se a reserva microvascular isquêmica periférica mediante a associação dos testes hiperemia reativa pós-oclusão e índice de perfusão periférica. Adicionalmente, amostras de sangue venoso periférico foram coletadas para avaliar os níveis dos neuropeptídeos substância P e peptídeo relacionado ao gene da calcitonina no membro superior do paciente antes e imediatamente após o teste de hiperemia reativa pós-oclusão. RESULTADOS: Não houve correlação estatisticamente significativa (p > 0,05) entre os valores basais ou variações dos níveis de neuropeptídeos e a reserva microvascular isquêmica periférica. CONCLUSÃO: Embora o peptídeo relacionado ao gene da calcitonina e a substância P possam desempenhar papel prognóstico na sepse, esses neuropeptídeos não parecem contribuir para a reserva microvascular isquêmica periférica.

O valor prognóstico da reserva microvascular isquêmica periférica na sepse não está vinculado ao peptídeo relacionado ao gene da calcitonina ou à substância P / The prognostic value of peripheral ischemic microvascular reserve in sepsis is not related to calcitonin gene-related peptide or substance P

RESUMO Objetivo: Avaliar possíveis mecanismos atribuídos ao valor prognóstico da reserva microvascular isquêmica periférica em pacientes com sepse. Métodos: Este estudo de coorte observacional incluiu 46 pacientes consecutivos com sepse em uma unidade de terapia intensiva entre novembro de 2020 e outubro de 2021. Após a ressuscitação volêmica com fluidos, avaliou-se a reserva microvascular isquêmica periférica mediante a associação dos testes hiperemia reativa pós-oclusão e índice de perfusão periférica. Adicionalmente, amostras de sangue venoso periférico foram coletadas para avaliar os níveis dos neuropeptídeos substância P e peptídeo relacionado ao gene da calcitonina no membro superior do paciente antes e imediatamente após o teste de hiperemia reativa pós-oclusão. Resultados: Não houve correlação estatisticamente significativa (p > 0,05) entre os valores basais ou variações dos níveis de neuropeptídeos e a reserva microvascular isquêmica periférica. Conclusão: Embora o peptídeo relacionado ao gene da calcitonina e a substância P possam desempenhar papel prognóstico na sepse, esses neuropeptídeos não parecem contribuir para a reserva microvascular isquêmica periférica.

ABSTRACT Objective: To evaluate the mechanisms attributed to the prognostic value of peripheral ischemic microvascular reserve in patients with sepsis. Methods: This observational cohort study enrolled 46 consecutive septic patients in the intensive care unit between November 2020 and October 2021. After fluid resuscitation, the peripheral ischemic microvascular reserve was evaluated using the association of postocclusion reactive hyperemia with the peripheral perfusion index. Additionally, peripheral venous blood samples were used to evaluate the neuropeptide calcitonin gene-related peptide and substance P levels in the upper limb before and immediately after postocclusion reactive hyperemia Results: There was no statistically significant correlation (p > 0.05) between basal values (pg/mL) or variations from neuropeptide levels (%) and the peripheral ischemic microvascular reserve (%). Conclusion: Although calcitonin gene-related peptide and substance P may have a prognostic role in sepsis, these neuropeptides do not appear to contribute to peripheral ischemic microvascular reserve.

The Therapeutic Value of Hydralazine in Reducing Inflammatory Response, Oxidative Stress, and Mortality in Animal Sepsis: Involvement of the PI3K/AKT Pathway.

ABSTRACT: Sepsis is an amplified systemic immune-inflammatory response produced by a microorganism, which involves activation of inflammatory cytokine signaling pathways and oxidative stress. A variety of studies have shown that hydralazine (HDZ) has potent antioxidant and anti-inflammatory proprieties. Therefore, we hypothesize that HDZ can improve the clinical outcome of sepsis. Thus, this work aimed to evaluate therapeutic value of HDZ in reducing inflammatory response, oxidative stress, and mortality in animal sepsis, and to investigate its possible mechanism of action. Sepsis was induced by the cecal ligation and puncture (CLP) method in Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis, and sepsis + HDZ (1 mg/kg, s.c.). All groups were monitored for 48 h to assess survival rate, and clinical, hemodynamic, biochemical, and cellular parameters. After euthanasia, blood, spleen, liver, and kidneys were collected for analysis. Blood serum cytokines, tissue myeloperoxidase (MPO) activity, and oxidative stress parameters were assessed. Involvement of the PI3K/Akt pathway was also investigated. Sepsis was successfully induced by the CLP technique. HDZ treatment increased the survival rate (from 50% to 90%), improved glycemia control, reduced the clinical severity sepsis and mean arterial pressure; and prevented increased MPO activity, TNF-α, IL-1ß, IL-10 levels, and oxidative damage markers. Additionally, HDZ significantly prevented the increase of Akt activation in the liver and kidney. HDZ largely mitigated the effects of sepsis by suppressing inflammatory and antioxidant responses via the PI3K/Akt pathway. These findings provide evidence that HDZ can be a new therapeutic alternative for treating sepsis.

Monoterpenes and their derivatives as agents for cardiovascular disease management: A systematic review and meta-analysis.

BACKGROUND: Monoterpenes are one of the most studied plant's secondary metabolites, they are found abundantly in essential oils of aromatic plants. They also have a great range of pharmacological properties, such as antihypertensive, bradycardic, antiarrhythmic and hypotensive. In the face of the burden caused by cardiovascular disease (CVDs) worldwide, studies using monoterpenes to assess their cardiovascular effects have increased over the years. PURPOSE: This systematic review aimed to summarize the use of monoterpenes in animal models of any CVDs. METHODS: PubMed, SCOPUS, LILACS and Web of Science databases were used to search for articles that used monoterpenes, in any type of administration, to treat or prevent CVDs in animal models. The PRISMA guidelines were followed. Two independent researchers extracted main characteristics of studies, methods and outcomes. Data obtained were analyzed qualitatively and quantitatively. RESULTS: At the ending of the search process, 33 articles were selected for the systematic review. Of these, 17 articles were included in the meta-analysis. A total of 16 different monoterpenes were found for the treatment of hypertension, myocardial infarction, pulmonary hypertension, cardiac hypertrophy and arrhythmia. The main actions include hypotension, bradycardia, vasodilatation, antiarrhythmic, and antioxidant and antiapoptotic properties. From our data, it can be suggested that monoterpenes may be a significant source for new drug development. However, there is still a need to apply these knowledge into clinical research and a long path to pursue before putting them in the market. CONCLUSION: The variability of cardiovascular effects demonstrated by the monoterpenes highlighted them as a promising candidates for treatment or prevention of CVDs. Nevertheless, studies that investigate their biological sites of action needs to be further encouraged.

Monitoring peripheral perfusion in sepsis associated acute kidney injury: Analysis of mortality.

Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.

[Association between peripheral perfusion, microcirculation and mortality in sepsis: a systematic review]. / Associação entre perfusão periférica, microcirculação e mortalidade em sepse: uma revisão sistemática.

Although increasing evidence supports the monitoring of peripheral perfusion in septic patients, no systematic review has been undertaken to explore the strength of association between poor perfusion assessed in microcirculation of peripheral tissues and mortality. A search of the most important databases was carried out to find articles published until February 2018 that met the criteria of this study using different keywords: sepsis, mortality, prognosis, microcirculation and peripheral perfusion. The inclusion criteria were studies that assessed association between peripheral perfusion/microcirculation and mortality in sepsis. The exclusion criteria adopted were: review articles, animal/pre-clinical studies, meta-analyzes, abstracts, annals of congress, editorials, letters, case-reports, duplicate and articles that did not present abstracts and/or had no text. In the 26 articles were chosen in which 2465 patients with sepsis were evaluated using at least one recognized method for monitoring peripheral perfusion. The review demonstrated a heterogeneous critically ill group with a mortality-rate between 3% and 71% (median=37% [28%-43%]). The most commonly used methods for measurement were Near-Infrared Spectroscopy (NIRS) (7 articles) and Sidestream Dark-Field (SDF) imaging (5 articles). The vascular bed most studied was the sublingual/buccal microcirculation (8 articles), followed by fingertip (4 articles). The majority of the studies (23 articles) demonstrated a clear relationship between poor peripheral perfusion and mortality. In conclusion, the diagnosis of hypoperfusion/microcirculatory abnormalities in peripheral non-vital organs was associated with increased mortality. However, additional studies must be undertaken to verify if this association can be considered a marker of the gravity or a trigger factor for organ failure in sepsis.

Association between peripheral perfusion, microcirculation and mortality in sepsis: a systematic review / Associação entre perfusão periférica, microcirculação e mortalidade em sepse: uma revisão sistemática

Abstract Although increasing evidence supports the monitoring of peripheral perfusion in septic patients, no systematic review has been undertaken to explore the strength of association between poor perfusion assessed in microcirculation of peripheral tissues and mortality. A search of the most important databases was carried out to find articles published until February 2018 that met the criteria of this study using different keywords: sepsis, mortality, prognosis, microcirculation and peripheral perfusion. The inclusion criteria were studies that assessed association between peripheral perfusion/microcirculation and mortality in sepsis. The exclusion criteria adopted were: review articles, animal/pre-clinical studies, meta-analyzes, abstracts, annals of congress, editorials, letters, case-reports, duplicate and articles that did not present abstracts and/or had no text. In the 26 articles were chosen in which 2465 patients with sepsis were evaluated using at least one recognized method for monitoring peripheral perfusion. The review demonstrated a heterogeneous critically ill group with a mortality-rate between 3% and 71% (median = 37% [28%-43%]). The most commonly used methods for measurement were Near-Infrared Spectroscopy (NIRS) (7 articles) and Sidestream Dark-Field (SDF) imaging (5 articles). The vascular bed most studied was the sublingual/buccal microcirculation (8 articles), followed by fingertip (4 articles). The majority of the studies (23 articles) demonstrated a clear relationship between poor peripheral perfusion and mortality. In conclusion, the diagnosis of hypoperfusion/microcirculatory abnormalities in peripheral non-vital organs was associated with increased mortality. However, additional studies must be undertaken to verify if this association can be considered a marker of the gravity or a trigger factor for organ failure in sepsis.

Resumo Embora evidências crescentes apoiem a monitoração da perfusão periférica em pacientes sépticos, nenhuma revisão sistemática foi feita para explorar a força da associação entre a má perfusão avaliada na microcirculação dos tecidos periféricos e a mortalidade. Uma busca nas bases de dados mais importantes foi feita para encontrar artigos publicados até fevereiro de 2018 que correspondessem aos critérios deste estudo, com diferentes palavras-chave: sepse, mortalidade, prognóstico, microcirculação e perfusão periférica. Os critérios de inclusão foram estudos que avaliaram a associação entre perfusão/microcirculação periférica e mortalidade em sepse. Os critérios de exclusão adotados foram os seguintes: artigos de revisão, estudos com animais/pré-clínicos, metanálises, resumos, anais de congressos, editoriais, cartas, relatos de casos, artigos duplicados e artigos que não continham resumos e/ou texto. Foram selecionados 26 artigos nos quais 2465 pacientes com sepse foram avaliados com pelo menos um método reconhecido para monitorar a perfusão periférica. A revisão demonstrou um grupo heterogêneo de pacientes gravemente enfermos com uma taxa de mortalidade entre 3% e 71% (mediana = 37% [28%-43%]). Os métodos de avaliação mais comumente usados foram a espectroscopia na região do infravermelho próximo (Near-Infrared Spectroscopy - NIRS) (7 artigos) e a análise de imagens em campo escuro (Sidestream Dark-Field - SDF) (5 artigos). O leito vascular mais avaliado foi a microcirculação sublingual/bucal (8 artigos), seguida pela ponta do dedo (4 artigos). A maioria dos estudos (23 artigos) demonstrou uma clara relação entre má perfusão periférica e mortalidade. Em conclusão, o diagnóstico de hipoperfusão/anormalidades microcirculatórias em órgãos não vitais periféricos foi associado ao aumento da mortalidade. No entanto, estudos adicionais devem ser feitos para verificar se essa associação pode ser considerada um marcador da gravidade ou um fator desencadeante da falência de órgãos na sepse.

Evidências de validade na adaptação do Orpheus Business Personality Inventory no Brasil / Evidence of validity in the Orpheus Business Personality Inventory adaptation in Brazil / Evidencias de validez en la adaptación del Orpheus Business Personality Inventory en Brasil

O propósito deste trabalho foi apresentar as evidências de validade do Orpheus Business Personality Inventory para a população brasileira. Cinco juízes contribuíram para a investigação das evidências de validade de conteúdo. Participaram deste estudo 938 indivíduos. Para investigar as evidências de validade de construto, utilizou-se a Full Information Factor Analysis. Os resultados deste estudo exploratório identificaram um conjunto de itens com cargas fatoriais baixas. O alfa de Cronbach e o coeficiente Omega foram calculados para medir a confiabilidade das escalas, seus valores variaram de 0,65 a 0,77 e de 0,53 a 0,77, respectivamente. Também foram avaliadas medidas de misfit usando o modelo Rasch, todos os itens apresentaram valores adequados. Estudo futuros são necessários para definir com clareza a sua adaptabilidade à população, entretanto foi possível demonstrar evidências de validade de conteúdo, estrutura interna e estabilidade teste-reteste para o OBPI, que poderá ser um importante instrumento de seleção nas organizações brasileiras.

The purpose of this work was to present evidences of validity for Orpheus Business Personality Inventory to the Brazilian population. Five experts contributed to the investigation of evidence content validity. In total, 938 individuals responded the test. To examine the evidences of construct validity, a Full Information Factor Analysis was carried out. The results of this exploratory study identified a group of items with low factor loadings. Cronbach's alpha and omega coefficient were calculated to measure reliability in the scales, their values varied from .65 to .77, and from .53 to .77, respectively. Misfit measurements were also deployed using Rasch model all items presented adequate values. Future studies are needed to clearly define the adaptability to the population; however, the quality of the psychometric properties could be testified through evidences of content validity, internal structure and stability test-retest for OBPI, test-retest stability for OBPI, which may be an important selection test in Brazilian organizations.

El propósito de este trabajo fue presentar las evidencias de validez del Orpheus Business Personality Inventory para la población brasileña. Cinco jueces contribuyeron a la investigación de las evidencias de validez de contenido. Participaron de este estudio 938 individuos. Los datos fueron recolectados en la plataforma Concerto. Para investigar las evidencias de validez de constructo, se utilizó el Full Information Factor Analysis. Los resultados de este estudio exploratorio identificaron un conjunto de ítems con cargas factoriales bajas. El alfa de Cronbach y el coeficiente Omega fueron calculados para medir la confiabilidad de las escalas, sus valores variaron de 0,65 a 0,77 y de 0,53 a 0,77, respectivamente. También se evaluaron medidas de misfit usando el modelo Rasch, todos los elementos presentaron valores adecuados. Los estudios futuros son necesarios para definir con claridad su adaptabilidad a la población, sin embargo fue posible demostrar evidencias de validez de contenido, estructura interna y estabilidad test-reteste para el OBPI, que podrá ser un importante instrumento de selección en las organizaciones brasileñas.

Increase of Perfusion Index During Vascular Occlusion Test is Paradoxically Associated With Higher Mortality in Septic Shock After Fluid Resuscitation: A Prospective Study.

Microcirculation disturbances imply poor prognosis in septic shock. Microvascular reserve can be assessed by oximetry-derived Perfusion Index (PI) after vascular occlusion test (VOT). We investigated the relationship between PI during VOT, hyperlactatemia and mortality in septic shock and the role of adrenergic stimulus in these findings. The tests were performed in 106 patients within 24 h after admission. PI was evaluated before/after 03-min flow occlusion. Peaks of PI (ΔPI peak) and time-to-peak were evaluated. PI was also evaluated in hyperemic phases derived by mechanosensitive (ΔPI0-60) and metabolic mechanisms (ΔPI60-120). We compared nonsurvivors with survivors and patients with lowest and highest ΔPI peaks, divided by 50th percentile. ΔPI peak was evaluated in presence/absence of hyperlactatemia. A correlation test between ΔPI peaks and noradrenaline doses and an assessment after doses increasing were also performed. The ΔPI peak values were higher in nonsurvivors [79% (47%-169%) vs. 48% (25%-85%); P=0.003] although peaks were reached slower in nonsurvivors. ΔPI0-60 was similar between groups [-12% (-42% to 28%) vs. 01% (-16%-23%); P = 0.211]. However, ΔPI60-120 was higher in nonsurvivors [49% (29%-84%) vs. 31% (12%-65%); P = 0.035]. Additionally, the group with higher ΔPI peaks had higher mortality than those with lower peaks [HR 2.25 (95% CI = 1.32-4.14); P = 0.003]. Mortality was extremely high in the presence of hyperlactatemia. ΔPI peaks were positively correlated with noradrenaline doses and increased after increasing doses.In conclusion, high values of PI during VOT indicate higher mortality in septic shock and are associated with adrenergic stimulus. Additionally, the assessment of PI-VOT appears to improve the predictive value of arterial lactate.

An evidence-based policy for improving choice in global health access through medical travel.

Global medical travel has had an increasing trend without a comprehensive, evidence-driven policy to ensure safe and effective practice. To identify key factors that influence medical travel, we conducted a series of studies culminating with a preference and decision-making component of over 500 prospective medical travelers from a number of countries. Results indicated that quality of care was the most critical factor in the decision, followed by lower costs of procedure and shorter waiting times. Lower costs were less of a factor if the procedure was more invasive, which also increased the importance of waiting time in the decision. The most desired destinations for care were in Europe (United Kingdom, Germany) and North America (United States). Building on these insights and previous literature, we present a model that implements applications from these factors and additional insights generated across the series of studies toward an effective policy framework.

Atributos Desejáveis de Parceiro Ideal: Podem Variar Segundo o Sexo e o Lugar de Residência? / Atributos Deseables de la Pareja Ideal: ¿Pueden Variar Según el Sexo y el Lugar de Residencia? / Desirable Attributes in the Ideal Partner: Can they Vary According to Gender and Place of Residence?

Resumo Compreender a escolha por parceiros amorosos é relevante no sentido de minimizar possíveis problemas decorrentes de relacionamentos conflituosos. Este estudo objetivou conhecer em que medida a preferência por atributos desejáveis de um parceiro ideal varia segundo o sexo e o local de residência das pessoas. Participaram do estudo 3.124 indivíduos residentes em capitais (n = 1.583) ou cidades do interior (n = 1.541) dos nove estados do Nordeste brasileiro, com idade média de 23,6 anos (dp = 6,72), sendo 63,6% do sexo feminino. Estes responderam a Escala de Atributos Desejáveis do Parceiro Ideal e perguntas demográficas. Os resultados (Manova) mostraram diferenças nos atributos desejáveis de um parceiro ideal segundo o sexo: os homens deram maior importância ao componente atlética, enquanto as mulheres pontuaram mais alto no componente realizada. Observou-se ainda efeito do lugar de residência, onde os homens residentes no interior apresentaram maior média no atributo tradicional, ao passo que as mulheres residindo nesta localidade deram mais importância ao atributo realizada. Concluiu-se que o lugar de residência e, sobretudo, o sexo foram importantes para explicar as variações na preferência por atributos de um parceiro ideal, na direção prevista na literatura.

Resumen Comprender la selección de parejas sentimentales es importante para minimizar los problemas potenciales que surgen de las relaciones románticas en conflicto. El objetivo de este estudio ha sido conocer en qué medida la preferencia por los atributos deseables de una pareja ideal varía según el sexo y el lugar de residencia de las personas. Participaron de la investigación 3.124 personas residiendo en la capital (n = 1.583) o ciudades del interior (n = 1.541) de los nueve estados del Noreste de Brasil, con una edad promedia de 23.6 años (de = 6.72), (63.6% mujeres). Éstos contestaron a la Escala de Atributos Deseables de una Pareja Ideal y cuestiones demográficas. Los resultados (Manova) indicaron diferencias en los atributos deseables de una pareja ideal según el sexo: los varones han dado mayor importancia al componente atlético, mientras que las mujeres puntuaron más alto en el componente realizada. También se ha observado efecto del lugar de residencia, en que los varones residentes en el interior dieron mayor importancia al atributo tradicional, mientras que las mujeres residiendo en esta localidad consideraron más importante el atributo atlético. Se concluyó que el lugar de residencia y, sobre todo, el sexo han sido importantes para explicar las variaciones en las preferencias por atributos de una pareja ideal, coherente con la literatura.

Abstract Comprehending the choice of romantic partner is important in order to minimize possible problems stemming from conflictive loving relationships. This study aimed to identify to what extent the preference for desirable attributes in an ideal partner vary according to the respondent's gender and place of residence. A total of 3,124 people from capital cities (n = 1,583) or towns (n = 1,541) of the nine states of the Brazilian Northeast region participated in the study, with a mean age of 23.6 years (sd = 6.72) and 63.6% female. They answered the Desirable Attributes of the Ideal Partner Scale and demographic questions. Results (Manova) indicated differences in the desirable attributes in an ideal partner according to gender: the men gave greater importance to the athletic dimension, while the women scored higher in the accomplished dimension. An effect was also observed related to the place of residence, with the men living in towns presenting a higher mean score in the traditional dimension, whereas the women residing in this locality gave more importance to the athletic dimension. In conclusion, the place of residence and, above all, the gender were important in explaining the variations in preferences for attributes in an ideal partner, in agreement with the literature.

Perfusion index for assessing microvascular reactivity in septic shock after fluid resuscitation. / Uso do índice de perfusão para avaliar reatividade microvascular no choque séptico após ressuscitação volêmica.

OBJECTIVE: Microcirculation disturbances are implicated in the prognosis of septic shock. Microvascular hyporesponsiveness can be assessed by an oximetry-derived perfusion index and reactive hyperemia. Using this perfusion index, we investigated reactive hyperemia and its relationship with peripheral perfusion and clinical-hemodynamic parameters in septic shock. METHODS: Eighty-two patients were evaluated: 47 with septic shock and 35 controls. Tests were performed within 24 hours after admission. The perfusion index was evaluated before and after a 3-min blood flow occlusion using a time-response analysis for 5 min. The perfusion index was also evaluated in the hyperemic phases and was mainly derived by mechanosensitive (ΔPI0-60) and metabolic mechanisms (ΔPI60-120). Correlation tests were performed between reactive hyperemia and clinical-hemodynamic data. RESULTS: Reactive hyperemia measured by the perfusion index was significantly lower in patients with septic shock, but this was only observed for the first 45 seconds after cuff-deflation. In the remaining period, there were no statistical differences between the groups. The peaks in the perfusion index were similar between groups, although the peak was reached more slowly in the septic group. Values of ΔPI0-60 were lower in shock [01% (-19% - -40%) versus 39% (6% - 75%); p = 0.001]. However, ΔPI60-120 was similar between the groups [43% (18% - 93%) versus 48% (18% - 98%); p = 0.58]. The time-to-peak of the perfusion index was correlated positively with the SOFA scores and negatively with C-reactive protein; the peak of the perfusion index was positively correlated with vasopressor doses; and the ΔPI60-120 values were positively correlated with C-reactive protein and vasopressor doses. No other significant correlations occurred. CONCLUSIONS: This perfusion index-based study suggests that septic shock promotes initial peripheral vascular hyporesponsiveness and preserves posterior vascular reactivity to a considerable degree. These results demonstrate a time-dependent peripheral hyperemic response and a significant ischemic reserve in septic shock.

OBJETIVO: Os distúrbios microcirculatórios estão implicados no prognóstico do choque séptico. A hiporresponsividade microvascular pode ser avaliada por meio do índice de perfusão, derivado da oximetria de pulso e hiperemia reativa. Com utilização do índice de perfusão, investigamos a hiperemia reativa e sua relação com a perfusão periférica e os parâmetros clínico-hemodinâmicos no choque séptico. MÉTODOS: Avaliaram-se 82 pacientes, 47 deles com choque séptico e 35 controles. Os exames foram realizados dentro de 24 horas após a admissão. O índice de perfusão foi avaliado antes e após uma oclusão do fluxo sanguíneo durante 3 minutos, utilizando-se análise de resposta temporal por 5 minutos. O índice de perfusão foi também avaliado nas fases hiperêmicas, principalmente com derivação de mecanismos mecanossensitivos (ΔIP0-60) e metabólicos (ΔIP60-120). Realizaram-se testes de correlação entre a hiperemia reativa e dados clínicos hemodinâmicos. RESULTADOS: A hiperemia reativa, medida pelo índice de perfusão, foi significantemente mais baixa no choque séptico apenas até 45 segundos após a desinflação do manguito. No período restante, não houve diferenças estatisticamente significantes entre os grupos. Os picos de índice de perfusão foram similares entre os grupos, embora o pico tenha sido atingido de forma mais lenta no grupo séptico. Os valores de ΔIP0-60 foram mais baixos no choque [1% (-19% - -40%) versus 39% (6% - 75%); p = 0,001]. No entanto, o ΔIP60-120 foi similar entre os grupos [43% (18% - 93%) versus 48% (18% - 98%); p = 0,58]. O tempo até o pico do índice de perfusão se correlacionou de forma positiva com o SOFA e negativamente com os níveis de proteína C-reativa. O pico de índice de perfusão se correlacionou de forma positiva com as doses de vasopressores; os valores de ΔIP60-120 tiveram correlação positiva com o nível de proteína C-reativa e as doses de vasopressores. Não ocorreram outras correlações significantes. CONCLUSÕES: Este estudo com base no índice de perfusão sugere que o choque séptico promove hiporresponsividade vascular periférica, enquanto a reatividade vascular posterior é consideravelmente preservada. Estes resultados demonstram resposta hiperêmica periférica dependente do tempo e significante reserva isquêmica no choque séptico.

Uso do índice de perfusão para avaliar reatividade microvascular no choque séptico após ressuscitação volêmica / Perfusion index for assessing microvascular reactivity in septic shock after fluid resuscitation

RESUMO Objetivo: Os distúrbios microcirculatórios estão implicados no prognóstico do choque séptico. A hiporresponsividade microvascular pode ser avaliada por meio do índice de perfusão, derivado da oximetria de pulso e hiperemia reativa. Com utilização do índice de perfusão, investigamos a hiperemia reativa e sua relação com a perfusão periférica e os parâmetros clínico-hemodinâmicos no choque séptico. Métodos: Avaliaram-se 82 pacientes, 47 deles com choque séptico e 35 controles. Os exames foram realizados dentro de 24 horas após a admissão. O índice de perfusão foi avaliado antes e após uma oclusão do fluxo sanguíneo durante 3 minutos, utilizando-se análise de resposta temporal por 5 minutos. O índice de perfusão foi também avaliado nas fases hiperêmicas, principalmente com derivação de mecanismos mecanossensitivos (ΔIP0-60) e metabólicos (ΔIP60-120). Realizaram-se testes de correlação entre a hiperemia reativa e dados clínicos hemodinâmicos. Resultados: A hiperemia reativa, medida pelo índice de perfusão, foi significantemente mais baixa no choque séptico apenas até 45 segundos após a desinflação do manguito. No período restante, não houve diferenças estatisticamente significantes entre os grupos. Os picos de índice de perfusão foram similares entre os grupos, embora o pico tenha sido atingido de forma mais lenta no grupo séptico. Os valores de ΔIP0-60 foram mais baixos no choque [1% (-19% - -40%) versus 39% (6% - 75%); p = 0,001]. No entanto, o ΔIP60-120 foi similar entre os grupos [43% (18% - 93%) versus 48% (18% - 98%); p = 0,58]. O tempo até o pico do índice de perfusão se correlacionou de forma positiva com o SOFA e negativamente com os níveis de proteína C-reativa. O pico de índice de perfusão se correlacionou de forma positiva com as doses de vasopressores; os valores de ΔIP60-120 tiveram correlação positiva com o nível de proteína C-reativa e as doses de vasopressores. Não ocorreram outras correlações significantes. Conclusões: Este estudo com base no índice de perfusão sugere que o choque séptico promove hiporresponsividade vascular periférica, enquanto a reatividade vascular posterior é consideravelmente preservada. Estes resultados demonstram resposta hiperêmica periférica dependente do tempo e significante reserva isquêmica no choque séptico.

ABSTRACT Objective: Microcirculation disturbances are implicated in the prognosis of septic shock. Microvascular hyporesponsiveness can be assessed by an oximetry-derived perfusion index and reactive hyperemia. Using this perfusion index, we investigated reactive hyperemia and its relationship with peripheral perfusion and clinical-hemodynamic parameters in septic shock. Methods: Eighty-two patients were evaluated: 47 with septic shock and 35 controls. Tests were performed within 24 hours after admission. The perfusion index was evaluated before and after a 3-min blood flow occlusion using a time-response analysis for 5 min. The perfusion index was also evaluated in the hyperemic phases and was mainly derived by mechanosensitive (ΔPI0-60) and metabolic mechanisms (ΔPI60-120). Correlation tests were performed between reactive hyperemia and clinical-hemodynamic data. Results: Reactive hyperemia measured by the perfusion index was significantly lower in patients with septic shock, but this was only observed for the first 45 seconds after cuff-deflation. In the remaining period, there were no statistical differences between the groups. The peaks in the perfusion index were similar between groups, although the peak was reached more slowly in the septic group. Values of ΔPI0-60 were lower in shock [01% (-19% - -40%) versus 39% (6% - 75%); p = 0.001]. However, ΔPI60-120 was similar between the groups [43% (18% - 93%) versus 48% (18% - 98%); p = 0.58]. The time-to-peak of the perfusion index was correlated positively with the SOFA scores and negatively with C-reactive protein; the peak of the perfusion index was positively correlated with vasopressor doses; and the ΔPI60-120 values were positively correlated with C-reactive protein and vasopressor doses. No other significant correlations occurred. Conclusions: This perfusion index-based study suggests that septic shock promotes initial peripheral vascular hyporesponsiveness and preserves posterior vascular reactivity to a considerable degree. These results demonstrate a time-dependent peripheral hyperemic response and a significant ischemic reserve in septic shock.