Personalized medicine, endotypes, and intensive care medicine

Wong, Hector R.

doi:10.1007/s00134-015-3812-3

Cited by 7 publications

(6 citation statements)

References 13 publications

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“…In the very recent years, the enormous heterogeneity of sepsis syndrome has pushed researchers to adopt the concept of “personalized medicine” [ 4 ] which mainly refers to a biomarker-guided therapy. The large involvement of organs and cell systems in the inflammatory response has widened the number of possible candidates and many new biomarkers are being explored.…”

Section: Introductionmentioning

confidence: 99%

Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

Carrara

Baselli

Ferrario

2015

Computational and Mathematical Methods in Medicine

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We studied the problem of mortality prediction in two datasets, the first composed of 23 septic shock patients and the second composed of 73 septic subjects selected from the public database MIMIC-II. For each patient we derived hemodynamic variables, laboratory results, and clinical information of the first 48 hours after shock onset and we performed univariate and multivariate analyses to predict mortality in the following 7 days. The results show interesting features that individually identify significant differences between survivors and nonsurvivors and features which gain importance only when considered together with the others in a multivariate regression model. This preliminary study on two small septic shock populations represents a novel contribution towards new personalized models for an integration of multiparameter patient information to improve critical care management of shock patients.

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Section: Introductionmentioning

confidence: 99%

Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

Carrara

Baselli

Ferrario

2015

Computational and Mathematical Methods in Medicine

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“…pain management based on genetics [8], treatment of sepsis based on genetic subtype [9,10] and organ failure endotype [11,12], and antibiotic dosing determined by individual blood levels [13,14]) (Fig. 1).…”

Section: "Prediction Is Very Difficult Especially About the Future" mentioning

confidence: 99%

Visit to intensive care of 2050

2016

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“…Significant attention has been devoted to the concept of sepsis “endotypes [21]; subclasses of patients that fall under the diagnosis of septic shock but differ significantly (as the result of different genetic background, sepsis etiology or co-morbidities) to the result that they require different therapeutic strategies. Here we suggest, for the first time, that distinct etiological endotypes may exist within the diagnosis of Sepsis-Induced Cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

Distinct Myocardial Mechanisms Underlie Cardiac Dysfunction in Endotoxemic Male and Female Mice

Hobai

Aziz

Buys

et al. 2016

Shock

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In male mice, Sepsis-Induced Cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca2+) handling, leading to depressed cellular Ca2+ transients (ΔCai). ΔCai depression is partially due to inhibition of sarcoplasmic reticulum Ca2+ ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie Sepsis-Induced Cardiomyopathy in female mice is unknown. Male and female C57Bl/6J mice (WT), and mice deficient in the sGC α1 subunit activity (sGCα1-/-) were challenged with lipopolysaccharide (LPS, ip). LPS-induced mouse death and cardiomyopathy (manifested as the depression of left ventricular ejection fraction, LVEF, by echocardiography) to a similar degree in WT male, WT female and sGCα1-/- male mice, but significantly less in sGCα1-/- female mice. We measured Sarcomere Shortening and ΔCai in isolated, externally paced cardiomyocytes, at 37 °C. LPS depressed Sarcomere Shortening in both WT male and female mice. Consistent with previous findings, in male mice, LPS induced a decrease in ΔCai (to 30 ± 2% of baseline) and SERCA inhibition (manifested as the prolongation of the time constant of Ca2+ decay, τCa, to 150 ±5% of baseline). In contrast, in female mice, the depression of Sarcomere Shortening induced by LPS occurred in the absence of any change in ΔCai, or SERCA activity. This suggested that, in female mice, the causative mechanism lies downstream of the Ca2+ transients, such as a decrease in myofilament sensitivity for Ca2+. The depression Sarcomere Shortening after LPS was less severe in female sGCα1-/- mice showed (to 69 ± 7% of baseline) than in WT female mice, indicating that cGMP partially mediates cardiomyocyte dysfunction. These results suggest, therefore, that LPS-induced cardiomyopathy develops through distinct sex-specific myocardial mechanisms. While in males LPS induces sGC-independent decrease in ΔCai, in female mice LPS acts downstream of ΔCai, possibly via sGC-dependent myofilament dysfunction.

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Personalized medicine, endotypes, and intensive care medicine

Cited by 7 publications

References 13 publications

Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

Visit to intensive care of 2050

Distinct Myocardial Mechanisms Underlie Cardiac Dysfunction in Endotoxemic Male and Female Mice

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