Traditional Metabolic Parameters Research Articles

Evaluation of microcirculatory changes after bundle therapy and prognostic value by the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure in the treatment of septic shock

To evaluate microcirculatory changes after bundle therapy and prognostic values of the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (PtcO2/PtcCO2) in the treatment of septic shock. A retrospective analysis was conducted. Patients with septic shock admitted to department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from July 2017 to February 2019 were enrolled. The gender, age, infection site, acute physiology and chronic health evaluation II (APACHE II), the length of ICU stay and 28-day prognosis were collected; PtcCO2, PtcO2, PtcO2/PtcCO2 ratio, arterial lactate (Lac), central venous oxygen saturation (ScvO2), mean arterial pressure (MAP) were measured before treatment (at admission) and 6 hours after bundle treatment. According to the 28-day prognosis, the patients were divided into survival group and death group, and the differences of each index between the two groups were compared. The risk factors of prognosis were analyzed by binary Logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the related indicators for the 28-day mortality of septic shock patients. A total of 78 patients with septic shock were enrolled, with 47 cases in survival group and 31 cases in death group. Compared with survival group, APACHE II score and PtcCO2 were higher and PtcO2/PtcCO2 ratio was lower in death group [APACHE II: 28.33±6.35 vs. 21.61±6.64, PtcCO2 (mmHg, 1 mmHg = 0.133 kPa): 51.80±19.05 vs. 38.17±6.79, PtcO2/PtcCO2 ratio: 1.20±0.72 vs. 1.80±0.81, all P < 0.05]. Compared with before treatment, the PtcO2/PtcCO2 ratio, Lac, MAP were substantially improved at 6 hours of bundle therapy [PtcO2/PtcCO2 ratio: 1.76±0.81 vs. 1.56±0.82, Lac (mmol/L): 3.74±2.40 vs. 4.42±2.60, MAP (mmHg): 83.34±7.58 vs. 71.00±5.36, all P < 0.05], and there was no changes in PtcCO2 and ScvO2. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy in the survival group was significantly higher than before treatment and was higher than that in death group (2.13±0.75 vs. 1.80±0.81, 1.19±0.53, both P < 0.05). There was no significant difference in PtcO2/PtcCO2 ratio of death group before and after treatment (1.19±0.53 vs. 1.20±0.72, P > 0.05). The binary Logistic regression showed that PtcO2/PtcCO2 ratio at 6 hours of bundle therapy and APACHE II score were risk factors of prognosis [PtcO2/PtcCO2 ratio: odds ratio (OR) = 7.876, P = 0.026; APACHE II score: OR = 0.846, P = 0.035]. ROC curve analysis showed that 6-hour of PtcO2/PtcCO2 ratio, APACHE II score and 6-hour Lac level could predict 28-day mortality in septic shock patients, and the area under curve (AUC) was 0.864, 0.784, and 0.752 respectively. The cut-off value of 6-hour PtcO2/PtcCO2 ratio for predicting mortality in septic shock patients was 1.42, the sensitivity was 87.0%, and the specificity was 73.3%. In addition, the patients were divided into two groups according to whether the 6-hour PtcO2/PtcCO2 ratio was greater than 1.42. The results showed that: compared with the PtcO2/PtcCO2 < 1.42 group, the APACHE II score in PtcO2/PtcCO2 ≥ 1.42 group was lower, the 6-hour Lac level was lower, 24-hour Lac reaching standard rate was higher and the 28-day mortality was lower. Compared with the traditional metabolic parameters, the improvement of early microcirculatory perfusion in patients with septic shock can reflect the effect of bundle therapy. The PtcO2/PtcCO2 ratio at 6 hours of bundle therapy can be used as a new index to predict the prognosis of patients with septic shock which supports the monitoring and evaluation of microcirculation in the early stage of treatment in septic shock.

An energetic reformulation of kinetic rate laws enables scalable parameter estimation for biochemical networks

The technology for building functionally complete or ‘whole-cell’ biological simulations is rapidly developing. However, the predictive capabilities of these simulations are hindered by the availability of parameter values, which are often difficult or even impossible to obtain experimentally and must therefore be estimated. Using E. coli’s glycolytic network as a model system, we describe and apply a new method which can estimate the values of all the system’s 102 parameters – fit to observations from studies of proteomics, metabolomics, enzyme kinetics and chemical energetics – and find that the resulting metabolic models are not only well-fit, but also dynamically stable. An analysis of how well parameter values in the network were determined by the training data revealed that over 80% of the parameter values were not well-specified. Moreover, the distribution of well-determined values was biased to a specific part of the network and against certain types of experimental data. Our results also suggest that perturbing the functional, energetic space of parameters (rather than traditional metabolic parameters) is a superior strategy for exploring the space of biological dynamics. The estimated parameter values matched both training data and previously withheld validation data within an order of magnitude for over 85% of the data points; notably, the area of greatest frustration in the network was also the most fully determined. Finally, our estimation method showed that fidelity to physiological observations such as network response time is enforced at the cost of fit to molecular parameter values. In summary, our reformulation enables estimation of accurate, biologically relevant parameters, generates insight into the biology of the simulated network, and appears generalizable to any biochemical network – potentially including whole-cell models.

Evaluation of endothelial dysfunction, endothelial plasma markers, and traditional metabolic parameters in children with adiposity.

To investigate the correlations among endothelial function assessment parameters, asymmetric dimethylarginine (ADMA)-related biomarkers, and traditional risk factors in adipose children. We enrolled adipose children aged 7-18 years between July 2014 and August 2016 as well as normal-weight controls from the outpatient clinic. Vascular measurements including echocardiography, carotid intima media thickness, pulse wave velocity (PWV), and flow-mediated dilation (FMD) were measured. Venous blood samples including traditional metabolic and endothelial dysfunction parameters were analyzed. Participants were grouped as adipose vs. normal-weight and as adipose with hypertension vs. adipose without hypertension. Clinical presentations, laboratory data, and cardiovascular measurement were compared. Of the 105 enrolled children, 85 were adipose. Adipose children had higher systolic blood pressure, larger left ventricular (LV) mass, and adverse traditional metabolic biomarkers. FMD was significantly reduced (8.25 (5.32-12.06) % vs. 12.49 (7.18-16.58) %, p=0.018) in the adipose group. PWV was markedly increased (4.65 (4.2-5.5)m/sec vs. 3.95 (3.38-4.35)m/sec, p<0.001) in the hypertensive adipose children. Endothelial dysfunction parameters were not significantly changed in this study. Adipose children were at higher risk of hypertension and LV hypertrophy. FMD, PWV and traditional cardiovascular biomarkers can detect subtle vascular changes. Hypertension is an important sign of arterial involvement in adipose children. Although ADMA-related biomarkers were not statistically significant, future studies are needed to confirm its correlation with adiposity and hypertension in children. The early detection and prevention of endothelial dysfunction may decrease the rate of progression to cardiovascular consequences in later life.

Disparities in Cardiovascular Disease and Type 2 Diabetes Risk Factors in Blacks and Whites: Dissecting Racial Paradox of Metabolic Syndrome.

Cardiovascular diseases (CVD) remain as the leading cause of mortality in the western world and have become a major health threat for developing countries. There are several risk factors that account for the CVD and the associated mortality. These include genetics, type 2 diabetes (T2DM), obesity, physical inactivity, hypertension, and abnormal lipids and lipoproteins. The constellation of these risk factors has been termed metabolic syndrome (MetS). MetS varies among racial and ethnic populations. Thus, race and ethnicity account for some of the differences in the MetS and the associated CVD and T2DM. Furthermore, the relationships among traditional metabolic parameters and CVD differ, especially when comparing Black and White populations. In this regard, the greater CVD in Blacks than Whites have been partly attributed to other non-traditional CVD risk factors, such as subclinical inflammation (C-reactive protein), homocysteine, increased low-density lipoprotein oxidation, lipoprotein a, adiponectin, and plasminogen activator inhibitor-1, etc. Thus, to understand CVD and T2DM differences in Blacks and Whites with MetS, it is essential to explore the contributions of both traditional and non-traditional CVD and T2DM risk factors in Blacks of African ancestry and Whites of Europoid ancestry. Therefore, in this mini review, we propose that non-traditional risk factors should be integrated in defining MetS as a predictor of CVD and T2DM in Blacks in the African diaspora in future studies.

Prognostic value of intratumoral metabolic heterogeneity on F-18 fluorodeoxyglucose positron emission tomography/computed tomography in locally advanced cervical cancer patients treated with concurrent chemoradiotherapy.

ObjectiveTo evaluate the prognostic value for predicting tumor recurrence of intratumoral metabolic heterogeneity and traditional quantitative metabolic parameters on pre-treatment F-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT).Materials and MethodsNinety-three patients with biopsy-proven cervical cancer and treated with CCRT (FIGO stage IIB-IV) were enrolled in this study. The traditional metabolic parameters of the primary tumor, regional lymph node, and whole body (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis), and intratumoral heterogeneity factor (HF) were measured on pre-treatment 18F-FDG PET/CT images. Univariate and multivariate analyses for disease-free survival (DFS) were performed using clinical and metabolic parameters. The additional HF prognostic value was evaluated by means of time-dependent receiver operating characteristic curve, integrated discrimination improvement, and net reclassification improvement.ResultsOn multivariate analysis, nodal SUVmax (hazard ratio 3.60; 95% CI, 1.66–7.85; p = 0.0012) and whole body MTV (WBMTV; hazard ratio 3.15; 95% CI, 1.17–8.53; p = 0.0236) were significant prognostic factors for DFS. When HF was combined with nodal SUVmax and WBMTV, a significant improvement in discrimination for recurrence was observed compared with nodal SUVmax alone (area under curve 0.817 vs. 0.732; p = 0.0028).ConclusionsHF did not show superiority over traditional metabolic parameters. However, when HF was combined with nodal SUVmax and WBMTV, the predictive value for tumor recurrence improved. Therefore, HF may be a useful additional prognostic biomarker to improve the prognostic value of traditional metabolic parameters on 18F-FDG PET/CT.

Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

PurposePerfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative evolution of peripheral vs metabolic perfusion parameters in septic shock resuscitation has not been studied. We conducted a prospective observational clinical-physiologic study to address this subject. MethodsPatients with sepsis-related circulatory dysfunction were resuscitated according to a standard local algorithm. Perfusion assessment included serial determinations of metabolic (central venous O2 saturation [Scvo2] and central venous to arterial Pco2 gradient [P(cv-a)co2]) and peripheral perfusion parameters (CRT and Tc-toe, among others). Successful resuscitation was defined as a normal plasma lactate at 24 hours. ResultsForty-one patients were included. The presence of normal values for both CRT and Tc-toe considered together at 6 hours was independently associated with a successful resuscitation (P = .02), as compared with the behavior of metabolic parameters. Capillary refill time was the first parameter to be significantly normalized. ConclusionEarly recovery of peripheral perfusion anticipates a successful resuscitation compared with traditional metabolic parameters in septic shock patients. Our findings support the inclusion of serial peripheral perfusion assessment in multimodal monitoring strategies for septic shock resuscitation.

Metabolic Evaluation of Children with Urolithiasis: Are Adult References for Supersaturation Appropriate?

We determined the incidence of urinary stone risk factors in pediatric patients with urolithiasis. Between 1998 and 2001, 71 children with urolithiasis at 2 pediatric institutions underwent metabolic evaluation. The 24-hour urine samples were analyzed outside central laboratory using adult and known pediatric references. Supersaturation and traditional metabolic parameters were determined and compared. All patients had metabolic abnormalities. Calcium related abnormalities were present in 92% of children, calcium oxalate supersaturation was abnormal in 69%, calcium phosphate supersaturation was elevated in 70% and traditional calcium parameters were abnormal in 80%. While 11% of the patients had abnormal calcium phosphate or oxalate supersaturation with normal traditional calcium parameters, 10% had normal calcium oxalate or phosphate supersaturation with abnormal traditional calcium parameters. Low urinary volume was identified in 75% of the children. Metabolic abnormalities are extremely common in pediatric patients with urolithiasis. Calcium related abnormalities are the most common abnormality. Urinary supersaturation values are complementary to traditional metabolic parameters and may be more sensitive predictors of recurrent stone risk. It is important to establish pediatric reference ranges to interpret these data more accurately.