Organ System Network Disruption in Nonsurvivors of Critically Ill Patients

Asada, Toshifumi; Aoki, Yuta; Sugiyama, Takehiro; Yamamoto, Miyuki; Ishii, Takeshi; Kitsuta, Youichi; Nakajima, Susumu; Yahagi, Naoki; Doi, Kent

doi:10.1097/ccm.0000000000001354

Cited by 26 publications

(37 citation statements)

References 35 publications

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“…These findings support the hypothesis that decreased organ system interaction is associated with poor prognosis in chronic liver failure. Our findings also continue to support previous studies suggesting that systemic dysfunction in acute life-threatening pathophysiology with multisystem involvement is attributed to a loss of homeostatic interorgan connectivity ( Buchman, 2002 ; Chovatiya and Medzhitov, 2014 ), most notably in the recent studies published by Asada et al (2016 , 2019) . Although our study explores multisystem disease of a chronic nature, the characteristics associated with poor prognosis in non-survivors remain similar, namely the breakdown of organ system connectivity, loss of homeostatic stability and isolation of individual organ system clusters.…”

Section: Discussionsupporting

confidence: 91%

“…Recently, Asada et al (2016) reported the first clinical application of network analysis to evaluate interorgan relationships between critically ill surviving and non-surviving patients with multiple organ failure. They challenged the reliability of conventional scoring methods, which sum up degrees of individual organ dysfunction to represent systemic illness pathophysiology and disease severity.…”

Section: Introductionmentioning

confidence: 99%

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Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure

2020

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Background: A healthy individual has a high degree of functional connectivity between organ systems, which can be represented graphically in a network map. Disruption of this system connectivity is associated with mortality in life-threatening acute illnesses, demonstrated by a network approach. However, this approach has not been applied to chronic multisystem diseases and may be more reliable than conventional individual organ prognostic scoring methods. Cirrhosis is a chronic disease of the liver with multisystem involvement. Development of an efficient model for prediction of mortality in cirrhosis requires a profound understanding of the pathophysiologic processes that lead to poor prognosis. In the present study, we use a network approach to evaluate the differences in organ system connectivity between survivors and non-survivors in a group of well-characterized patients with cirrhosis. Methods: 201 patients with cirrhosis originally referred to the Clinic five at the University Hospital of Padova, with 13 clinical variables available representing hepatic, metabolic, haematopoietic, immune, neural and renal organ systems were retrospectively enrolled and followed up for 3, 6, and 12 months. Software was designed to compute the correlation network maps of organ system interaction in survivors and non-survivors using analysis indices: A. Bonferroni corrected Pearson's correlation coefficient and B. Mutual Information. Network structure was quantitatively evaluated using the measures of edges, average degree of connectivity and closeness, and qualitatively using clinical significance. Pair-matching was also implemented as a further step after initial general analysis to control for sample size and Model for End-Stage Liver Disease (MELD-Na) score between the groups. Results: There was a higher number of significant correlations in survivors, as indicated by both the analysis indices of Bonferroni corrected Pearson's correlation coefficient and the Mutual Information analysis. The number of edges, average degree of connectivity and closeness were significantly higher in survivors compared to non-survivors group. Pair-matching for MELD-Na was also associated with increased connectivity in survivors compared to non-survivors over 3 and 6 months follow up. Conclusion: This study demonstrates the application of a network approach in evaluating functional connectivity of organ systems in liver cirrhosis, demonstrating a

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure

2020

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“…This study is a subanalysis of our prospective observational studies [ 24 – 26 ]. The cohort in this study was selected from these previous prospective observational studies conducted in the medical–surgical mixed ICU at the University of Tokyo Hospital.…”

Section: Methodsmentioning

confidence: 99%

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels

Matsuura

Komaru

Miyamoto

et al. 2018

Ann. Intensive Care

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BackgroundFurosemide responsiveness (FR) is determined by urine output after furosemide administration and has recently been evaluated as a furosemide stress test (FST) for predicting severe acute kidney injury (AKI) progression. Although a standardized furosemide dose is required for FST, variable dosing is typically employed based on illness severity, including renal dysfunction in the clinical setting. This study aimed to evaluate whether FR with different furosemide doses can predict AKI progression. We further evaluated the combination of an AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for predicting AKI progression.ResultsWe retrospectively analyzed 95 patients who were treated with bolus furosemide in our medical–surgical intensive care unit. Patients who had already developed AKI stage 3 were excluded. A total of 18 patients developed AKI stage 3 within 1 week. Receiver operating curve analysis revealed that the area under the curve (AUC) values of FR and plasma NGAL were 0.87 (0.73–0.94) and 0.80 (0.67–0.88) for AKI progression, respectively. When plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI, indicating that plasma NGAL measurements were sufficient to predict AKI progression. We further evaluated the performance of FR in 51 patients with plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67–0.94) for AKI progression in this population with high NGAL levels.ConclusionsAlthough different variable doses of furosemide were administered, FR revealed favorable efficacy for predicting AKI progression even in patients with high plasma NGAL levels. This suggests that a combination of FR and biomarkers can stratify the risk of AKI progression in a clinical setting.Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0355-0) contains supplementary material, which is available to authorized users.

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“…Future investigation can pave the way to understand the mechanism of these effects by using an electrophysiologic (direct vagus nerve recording) or pharmacologic approach. Development of new analytical methods in Network Physiology will also help to uncover the mechanism of multiple organ failure in cirrhosis form a different perspective (Bartsch et al 2015, Xiong et al 2017, Asada et al 2016, Ivanov et al 2016, Kanter et al 2015. For example, multiscale network construction (Shashikumar et al 2017) can be employed for quantification of cardiovascular and respiratory interaction within the context of sepsis in patients with liver failure.…”

Section: Discussionmentioning

confidence: 99%

The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure

et al. 2018

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The network of interactions between different organs is impaired in liver cirrhosis. Liver cirrhosis is associated with multi-system involvement which eventually leads to multiple organ failure. This process is accelerated by a precipitating factor such as bacterial infection which leads to respiratory distress, circulatory shock, neural dysfunction and very high mortality. Cirrhotic patients often have blunted respiratory sinus arrhythmia and impaired cardio-respiratory variability. Fractal-like mechanical ventilation is reported to enhance respiratory sinus arrhythmia and attenuate respiratory distress in experimental models. In present study we hypothesised that fractal-like mechanical ventilation may improve the outcome of cirrhotic rats with multiple organ failure. Cirrhosis was induced by chronic biliary obstruction in rats. Acute multiple organ failure was induced by intraperitoneal injection of bacterial endotoxin in cirrhotic rats. The effect of conventional mechanical ventilation (with constant tidal volume and respiratory rate) or fractal-like ventilation (with the same average but variable tidal volume and respiratory rate) were assessed on vital signs, oxygen saturation and plasma alanine aminotransferase in anaesthetised cirrhotic rats. We demonstrated that fractal-like mechanical ventilation was accompanied by improved oxygen saturation, reduced heart rate and decreased liver injury following injection of bacterial endotoxin. Moreover, variable mechanical ventilation in cirrhotic rats reduced mortality and prevented a fall in short-term heart rate variability following endotoxin challenge in comparison with rats with constant mechanical ventilation. We suggest further investigations on beneficial effects of fractal-like ventilation strategy in critically ill patients with liver failure requiring organ support and mechanical ventilation.

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Organ System Network Disruption in Nonsurvivors of Critically Ill Patients

Cited by 26 publications

References 35 publications

Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure

Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels

The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure

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