Echocardiographic features of right ventricle in septic patients with elevated central venous pressure.

BACKGROUND: Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. METHODS: We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. RESULTS: Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302-0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007-1.903, p = 0.045) were independently associated with 30-day mortality. CONCLUSIONS: Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.

Thiol-catalyzed formation of NO-ferroheme regulates intravascular NO signaling.

Nitric oxide (NO) is an endogenously produced signaling molecule that regulates blood flow and platelet activation. However, intracellular and intravascular diffusion of NO are limited by scavenging reactions with several hemoproteins, raising questions as to how free NO can signal in hemoprotein-rich environments. We explore the hypothesis that NO can be stabilized as a labile ferrous heme-nitrosyl complex (Fe2+-NO, NO-ferroheme). We observe a reaction between NO, labile ferric heme (Fe3+) and reduced thiols to yield NO-ferroheme and a thiyl radical. This thiol-catalyzed reductive nitrosylation occurs when heme is solubilized in lipophilic environments such as red blood cell membranes or bound to serum albumin. The resulting NO-ferroheme resists oxidative inactivation, is soluble in cell membranes and is transported intravascularly by albumin to promote potent vasodilation. We therefore provide an alternative route for NO delivery from erythrocytes and blood via transfer of NO-ferroheme and activation of apo-soluble guanylyl cyclase.

Effect of Glucose Contents on Electrochemical Corrosion Behavior of Ti/ZrO2 Brazing Joint in SBF.

The effect of glucose content on the electrochemical corrosion behavior of the Ti/ZrO2 brazing joint in simulated body fluid (SBF) was researched by the means of SEM morphologies, electrochemical and XPS analyses. Herein, pitting is observed to be a dominating corrosion model under the investigated glucose content. The pitting corrosion of the joint in 200 mg/dL SBF is minimal. In addition, the joint in 200 mg/dL SBF manifests the best corrosion resistance by electrochemical analyses, which indicates that glucose content has a bidirectional effect on corrosion of the Ti/ZrO2 brazing joint. Additionally, the corrosion current value and impedance of titanium and brazing joint are close, which indicates that their corrosion resistance is similar. Finally, the OH-, Cl-, Sn2+/Sn4+ and -COOH on the joint surface are found by XPS analysis, and the mechanism of Ti/ZrO2 brazing joint corrosion is elucidated. The study provides a novel understanding of the corrosion behavior and relevant corrosion mechanism of the Ti/ZrO2 brazing joint in body fluids with different glucose content.

Thiol catalyzed formation of NO-ferroheme regulates canonical intravascular NO signaling.

Nitric oxide (NO) is an endogenously produced physiological signaling molecule that regulates blood flow and platelet activation. However, both the intracellular and intravascular diffusion of NO is severely limited by scavenging reactions with hemoglobin, myoglobin, and other hemoproteins, raising unanswered questions as to how free NO can signal in hemoprotein-rich environments, like blood and cardiomyocytes. We explored the hypothesis that NO could be stabilized as a ferrous heme-nitrosyl complex (Fe 2+ -NO, NO-ferroheme) either in solution within membranes or bound to albumin. Unexpectedly, we observed a rapid reaction of NO with free ferric heme (Fe 3+ ) and a reduced thiol under physiological conditions to yield NO-ferroheme and a thiyl radical. This thiol-catalyzed reductive nitrosylation reaction occurs readily when the hemin is solubilized in lipophilic environments, such as red blood cell membranes, or bound to serum albumin. NO-ferroheme albumin is stable, even in the presence of excess oxyhemoglobin, and potently inhibits platelet activation. NO-ferroheme-albumin administered intravenously to mice dose-dependently vasodilates at low- to mid-nanomolar concentrations. In conclusion, we report the fastest rate of reductive nitrosylation observed to date to generate a NO-ferroheme molecule that resists oxidative inactivation, is soluble in cell membranes, and is transported intravascularly by albumin to promote potent vasodilation.

Prognostic implication of a novel right ventricular injury score in septic patients.

AIMS: We aim to investigate the prognostic value of a right ventricular (RV) injury score based on the concept of RV dilation, RV systolic dysfunction, and RV-pulmonary arterial (PA) decoupling in septic patients and to explore whether the RV injury (RVI) score can be used to grade the severity of RV dysfunction in these patients. METHODS AND RESULTS: Septic patients admitted to the ICU were prospectively included. We collected haemodynamic and echocardiographic parameters as well as prognostic information. RV dilation was defined as right and left ventricular end-diastolic area ratio (R/LVEDA) > 2/3. RVSD was defined as tricuspid annular plane systolic excursion (TAPSE) < 17 mm, right ventricular fractional area change (FAC) < 35%, or peak velocity of tricuspid annulus via tissue Doppler (S') < 10 cm/s. RV-PA decoupling was represented by the TAPSE/pulmonary arterial systolic pressure (PASP) ratio. RVI score were determined by the presence of the following findings: RVSD, RV dilation, and RV-PA decoupling, that is, one point for each finding. A total of 327 patients were enrolled in this study, among whom 276 survived and 51 died at 30 days after admission. Overall, 18.0% had RV dilation, 35.8% had RVSD, and 21.4% had RV-PA decoupling, with an appreciable overlap present. A multivariate Cox regression analysis showed that RV dilation (HR: 2.19, 95% CI: 1.19-4.01, P = 0.011), RVSD (HR: 2.25, 95% CI: 1.23-4.13, P = 0.009) and RV-PA decoupling (HR: 2.08, 95% CI: 1.19-3.65, P = 0.011) were independently associated with a 30 day mortality. Furthermore, RVI score was also an independent predictor, displayed additive effect with respect to 30 day mortality (RVI score 1 vs. RVI score 0, HR: 2.94, 95% CI: 1.20-7.20, P = 0.018; RVI score 2 vs. RVI score 0, HR: 3.20, 95% CI: 1.28-7.98, P = 0.013; RVI score 3 vs. RVI score 0, HR: 7.17, 95% CI: 2.65-19.38, P < 0.001), and had the best performance in model goodness of fit, discrimination and variance explained than the other RV indices. CONCLUSIONS: The RVI score was independently related to 30 day mortality and had the potential to grade the severity of RV dysfunction in septic patients.

Cell-free and alkylated hemoproteins improve survival in mouse models of carbon monoxide poisoning.

I.v. administration of a high-affinity carbon monoxide-binding (CO-binding) molecule, recombinant neuroglobin, can improve survival in CO poisoning mouse models. The current study aims to discover how biochemical variables of the scavenger determine the CO removal from the RBCs by evaluating 3 readily available hemoproteins, 2,3-diphosphoglycerate stripped human hemoglobin (StHb); N-ethylmaleimide modified hemoglobin (NEMHb); and equine myoglobin (Mb). These molecules efficiently sequester CO from hemoglobin in erythrocytes in vitro. A kinetic model was developed to predict the CO binding efficacy for hemoproteins, based on their measured in vitro oxygen and CO binding affinities, suggesting that the therapeutic efficacy of hemoproteins for CO poisoning relates to a high M value, which is the binding affinity for CO relative to oxygen (KA,CO/KA,O2). In a lethal CO poisoning mouse model, StHb, NEMHb, and Mb improved survival by 100%, 100%, and 60%, respectively, compared with saline controls and were well tolerated in 48-hour toxicology assessments. In conclusion, both StHb and NEMHb have high CO binding affinities and M values, and they scavenge CO efficiently in vitro and in vivo, highlighting their therapeutic potential for point-of-care antidotal therapy of CO poisoning.

Risk factors assessment in patients with acute fatty liver of pregnancy treated without plasma exchange or renal replacement therapy.

OBJECTIVE: Acute fatty liver of pregnancy(AFLP) is a rare but very urgent obstetric disease in clinical. It is a common cause of liver failure in pregnancy and often needs to be admitted to the department of critical care medicine because of the rapid development of acute hepatic dysfunction and severe acute renal dysfunction. The etiology and pathogenesis of this disorder is not very clear although there have been many studies on it before. Meanwhile, the relatively high mortality requires a better recognition in order to better guide clinical decision making. Our previous multicentre retrospective study on AFLP demonstrated that total bilirubin and serum creatinine were independent risk factors for perinatal maternal mortality. And we aim to further assess maternal outcomes and risk factors in AFLP patients treated without plasma exchange or renal replacement therapy based on previous data we collected. METHODS: Retrospective cohort study of 133 hospitalized patients with AFLP was collected from four Chinese tertiary hospitals during the period between January 2009 and April 2014. One hundred thirty three patients were divided into two subgroups containing patients treated without plasma exchange (PE) or renal replacement therapy (CRT) and patients treated with PE or/and CRT. Logistic regression was used to analyze independent risk factors for maternal mortality of AFLP treated without PE or CRT. RESULTS: The maternal mortality rate was 12.0% in subgroup of patients treated without PE or CRT. And in subgroup of patients treated with PE or/and CRT, the maternal mortality rate was 26.8%. Independent risk factors for maternal mortality of AFLP treated without PE or CRT were direct bilirubin (OR = 1.012; 95% CI, 1.002-1.022) and serum creatinine (OR = 1.022; 95% CI, 1.007-1.036). CONCLUSION: Although less liver and kidney damage in AFLP treated without PE or CRT, direct bilirubin and serum creatinine remained to be independent risk factors for maternal mortality. Thus, the level of bilirubin and serum creatinine might not be necessary for AFLP to decide whether to give plasma exchange or dialysis treatment.

Prevalence and prognostic value of various types of right ventricular dysfunction in mechanically ventilated septic patients.

INTRODUCTION: Right ventricle (RV) dilation in combination with elevated central venous pressure (CVP), which is a state of RV congestion, is seen as a sign of RV failure (RVF). On the other hand, RV systolic function is usually assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). This study aimed to investigate the prevalence and prognostic value of RVF and RV systolic dysfunction (RVSD) in septic patients. METHODS: Mechanically ventilated sepsis and septic shock patients were included. We collected haemodynamic and echocardiographic parameters as well as prognostic information including mechanical ventilation duration, length of ICU stay and 30-day mortality. RVF was defined as a right and left ventricular end-diastolic area ratio ≥ 0.6 in combination with CVP ≥ 8 mmHg. RVSD was defined as TAPSE < 16 mm or FAC < 35%. RESULTS: A total of 215 patients were enrolled in this study, and the patients were divided into 4 groups: patients with normal RV function (normal, n = 101), patients with RVF but without RVSD (RVF only, n = 38), patients with RVSD but without RVF (RVSD only, n = 44), and patients with combined RVF-RVSD (RVF/RVSD, n = 32). The RVF/RVSD group and RVSD only group had a lower cardiac index than the RVF only group and normal groups (p < 0.05). At 30 days after ICU admission, 50.0% of patients had died in the RVF/RVSD group, which was much higher than the mortality in the RVF only group (13.2%) and normal group (13.9%) (p < 0.05). In a Cox regression analysis, the presence of RVF/RVSD was independently associated with 30-day mortality (HR 3.004, 95% CI:1.370-6.587, p = 0.006). In contrast, neither the presence of RVF only nor the presence of RVSD only was associated with 30-day mortality (HR 0.951, 95% CI:0.305-2.960, p = 0.931; HR 1.912, 95% CI:0.853-4.287, p = 0.116, respectively). CONCLUSION: The presence of combined RVF-RVSD was associated with 30-day mortality in mechanically ventilated septic patients. Additional studies are needed to confirm and expand this finding.

Prognostic implications of tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio in septic shock patients.

BACKGROUND: To explore the association between the ratio of tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP), and long- and short-term outcomes in mechanically ventilated septic shock patients. METHODS: Septic shock patients admitted to the intensive care unit (ICU) were screened for enrollment. Echocardiographic parameters including TAPSE and tricuspid regurgitation velocity, haemodynamic and respiratory parameters, and prognostic data were obtained. RESULTS: One hundred eighteen subjects were enrolled in this study, among whom 75 survived and 43 died at the one-year follow-up. ROC curve analysis revealed that the TAPSE/PASP ratio was able to assess one-year all-cause mortality with an area under the curve of 0.817 (95% CI: 0.739-0.896, p < 0.001) and the optimal cutoff value was 0.50 mm/mmHg. Kaplan-Meier survival analysis showed that one-year all-cause mortality was significantly higher in patients with TAPSE/PASP ≤0.5 mm/mmHg than in patients with TAPSE/PASP > 0.5 mm/mmHg (log-rank 32.934, p < 0.001). According to the Cox regression survival analyses, the TAPSE/PASP ratio was independently associated with one-year all-cause mortality (HR 0.007, 95% CI:0.000-0.162, p = 0.002) and ICU mortality (HR 0.027, 95% CI:0.001-0.530, p = 0.017). According to the multivariable analysis, the TAPSE/PASP ratio was an independent variable associated with mechanical ventilation (MV) duration (standard coefficient - 0.240, p = 0.010). CONCLUSION: The TAPSE/PASP ratio demonstrated prognostic value for one-year all-cause mortality, ICU mortality and MV duration in mechanically ventilated septic shock patients.

Physicians' abilities to obtain and interpret focused cardiac ultrasound images from critically ill patients after a 2-day training course.

BACKGROUND: This study aimed to determine whether a focused 2-day cardiac ultrasound training course could enable physicians to obtain and interpret focused cardiac ultrasound (FCU) images from critically ill patients. METHODS: We retrospectively reviewed the FCU images submitted by the physicians who attended a 2-day FCU training courses. Three experienced trainers reviewed the images separately. They determined whether the images were assessable and scored the images on an 8-point scale. They also decided whether the physicians provided correct responses for visual estimations of the left ventricular ejection fraction (LVEF) and right ventricle (RV) dilatation and septal motion. RESULTS: Among the 327 physicians, 291 obtained images that were considered assessable (89%). The scores for parasternal short-axis view were lower than those obtained for other transthoracic echocardiographic views, p < 0.001. More physicians provided incorrect appraisals of LVEF than of RV dilatation and septal motion (19.9% vs. 3.1%, p < 0.001). The percentages of incorrect answers by LVEF category were as follows: 34.8% on images of LVEF < 30, 24.7% on images of LVEF 30-54, and 16.4% on images of LVEF ≥55%, p < 0.001. A logistic regression analysis showed that patients with abnormal LVEF were associated with physicians' incorrect assessment of LVEF, with an odds ratio of 1.923 (95% confidence interval (CI):1.071-3.456, p = 0.029). CONCLUSIONS: A large proportion of physicians could obtain and interpret FCU images from critically ill patients after a 2-day training course. However, they still scored low on the parasternal short-axis view and were more likely to make an incorrect assessment of LVEF in patients with abnormal left ventricular systolic function.

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC-treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 µm) and nitric oxide (100 µm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 µm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

Time-dependent effects of histone deacetylase inhibition in sepsis-associated acute kidney injury.

BACKGROUND: Sepsis, a dysregulated host response to infection with results in organ dysfunction, has been a major challenge to the development of effective therapeutics. Sepsis-associated acute kidney injury (S-AKI) results in a 3-5-fold increase in the risk of hospital mortality compared to sepsis alone. The development of therapies to reverse S-AKI could therefore significantly affect sepsis outcomes. However, the translation of therapies from preclinical studies into humans requires model systems that recapitulate clinical scenarios and the development of renal fibrosis indicative of the transition from acute to chronic kidney disease. RESULTS: Here we characterized a murine model of S-AKI induced by abdominal sepsis developing into a chronic phenotype. We applied a small molecule histone deacetylase-8 inhibitor, UPHD186, and found that early treatment, beginning at 48 h post-sepsis, worsened renal outcome accompanied by decreasing mononuclear cell infiltration in the kidney, skewing cells into a pro-inflammatory phenotype, and increased pro-fibrotic gene expression, while delayed treatment, beginning at 96 h post-sepsis, after the acute inflammation in the kidney had subsided, resulted in improved survival and kidney histology presumably through promoting proliferation and inhibiting fibrosis. CONCLUSIONS: These findings not only present a clinically relevant S-AKI model, but also introduce a timing dimension into S-AKI therapeutic interventions that delayed treatment with UPHD186 may enhance renal histologic repair. Our results provide novel insights into successful repair of kidney injury and sepsis therapy.

Prognostic Value of Tricuspid Annular Plane Systolic Excursion and Right Ventricular Outflow Tract Fractional Shortening in Mechanically Ventilated Septic Patients.

OBJECTIVE: The authors aimed to explore whether tricuspid annular plane systolic excursion (TAPSE) and right ventricular outflow fractional shortening (RVOT-FS) were associated with long-term prognosis in mechanically ventilated septic patients. DESIGN: A prospective observational study. SETTING: A tertiary hospital intensive care unit (ICU). PARTICIPANTS: One hundred eighty-one septic patients who were on mechanical ventilation. INTERVENTIONS: Echocardiography was performed within 24 hours of ICU admission. MEASUREMENTS AND MAIN RESULTS: Several echocardiographic parameters, including TAPSE and RVOT-FS, as well as prognostic information, were collected. A Cox regression survival analysis showed that TAPSE was independently associated with one-year all-cause mortality (hazard ratio [HR] 0.407, 95% confidence interval [CI]: 0.200-0.827, p = 0.013), but ROVT-FS was not (HR 0.997, 95% CI: 0.970-1.025, p = 0.828). ROC analysis showed that the optimal cutoff value for TAPSE and RVOT-FS to determine one-year mortality was TAPSE <18 mm and RVOT-FS <40%. The one-year mortality in patients with low TAPSE (n = 88) and in patients with both low TAPSE and low RVOT-FS (n = 60) was 45.5% and 48.3%, respectively; p = 0.724. In a multivariate analysis, RVOT-FS did not add significant prognostic information to that provided by TAPSE <18 mm (p = 0.197). CONCLUSIONS: TAPSE was an independent predictor of one-year all-cause mortality in mechanically ventilated septic patients. RVOT-FS was not associated with one-year mortality and added no prognostic value to TAPSE in these patients.

Respiratory variations of inferior vena cava fail to predict fluid responsiveness in mechanically ventilated patients with isolated left ventricular dysfunction.

BACKGROUND: Respiratory variation of inferior vena cava is problematic in predicting fluid responsiveness in patients with right ventricular dysfunction. However, its effectiveness in patients with isolated left ventricular systolic dysfunction (ILVD) has not been reported. We aimed to explore whether inferior vena cava diameter distensibility index (dIVC) can predict fluid responsiveness in mechanically ventilated ILVD patients. METHODS: Patients admitted to the intensive care unit who were on controlled mechanical ventilation and in need of a fluid responsiveness assessment were screened for enrolment. Several echocardiographic parameters, including dIVC, tricuspid annular plane systolic excursion (TAPSE), left ventricular ejection fraction (LVEF), and LV outflow tract velocity-time integral (VTI) before and after passive leg raising (PLR) were collected. Patients with LV systolic dysfunction only (TAPSE ≥ 16 mm, LVEF < 50%) were considered to have isolated left ventricular systolic dysfunction (ILVD). RESULTS: One hundred and twenty-nine subjects were enrolled in this study, among them, 28 were labelled ILVD patients, and the remaining 101 were patients with normal LV function (NLVF). The value of dIVC in ILVD patients was as high as that in NLVF patients, (20% vs. 16%, p = 0.211). The ILVD group contained a much lower proportion of PLR responders than NLVF patients did (17.9% vs. 53.2%, p < 0.001). No correlation was detected between dIVC and ΔVTI in ILVD patients (r = 0.196, p = 0.309). dIVC was correlated with ΔVTI in NLVF patients (r = 0.722, p < 0.001), and the correlation was strengthened compared with that derived from all patients (p = 0.020). A receiver-operating characteristic (ROC) analysis showed that the area-under-the-curve (AUC) of dIVC for determining fluid responsiveness from ILVD patients was not statistically significant (p = 0.251). In NLVF patients, ROC analysis revealed an AUC of 0.918 (95% CI 0.858-0.978; p < 0.001), which was higher than the AUC derived from all patients (p = 0.033). Patients with LVEF below 40% had a lower ΔVTI and fewer PLR responders than those with LVEF 40-50% and LVEF above 50% (p < 0.001). CONCLUSION: dIVC should be used with caution when critically ill patients on controlled mechanical ventilation display normal right ventricular function in combination with abnormal left ventricular systolic function.

Renal failure in critically ill patients, beware of applying (central venous) pressure on the kidney.

The central venous pressure (CVP) is traditionally used as a surrogate of intravascular volume. CVP measurements therefore are often applied at the bedside to guide fluid administration in postoperative and critically ill patients. Pursuing high CVP levels has recently been challenged. A high CVP might impede venous return to the heart and disturb microcirculatory blood flow which may cause tissue congestion and organ failure. By imposing an increased "afterload" on the kidney, an elevated CVP will particularly harm kidney hemodynamics and promote acute kidney injury (AKI) even in the absence of volume overload. Maintaining the lowest possible CVP should become routine to prevent and treat AKI, especially when associated with septic shock, cardiac surgery, mechanical ventilation, and intra-abdominal hypertension.

Tricuspid annular plane systolic excursion and central venous pressure in mechanically ventilated critically ill patients.

BACKGROUND: The tricuspid annular plane systolic excursion (TAPSE) is commonly recommended for estimating the right ventricular systolic function. The central venous pressure (CVP), which is determined by venous return and right heart function, was found to be associated with right ventricular outflow fractional shortening. This study thus aimed to investigate the relationship between the TAPSE and CVP in mechanically ventilated critically ill patients. METHODS: This is a prospective observational study. From October 1 to December 31, 2017, patients admitted to the intensive care unit with CVP monitoring and controlled mechanical ventilation were screened for enrolment. Echocardiographic parameters, including the TAPSE, mitral annular plane systolic excursion (MAPSE), left ventricular ejection fraction (LVEF), and internal diameter of inferior vena cava (dIVC), and haemodynamic parameters, including the CVP, were collected. RESULTS: Seventy-four patients were included. Thirty-one were included in the low LVEF (< 55%) group, and 43 were included in the high LVEF (≥55%) group. In the high LVEF group, the TAPSE and CVP were not correlated (r = - 0.234, P = 0.151). In the low LVEF group, partial correlation analysis indicated that the TAPSE and CVP were correlated (r = - 0.516, P = 0.006), and multivariable linear regression analysis indicated that the TAPSE was independently associated with the CVP (standard coefficient: - 0.601, p < 0.001). Additionally, in the low LVEF group, a ROC analysis showed that the area under the curve of the TAPSE for the detection of CVP greater than 8 mmHg was 0.860 (95% confidence interval: 0.730-0.991; P = 0.001). The optimum cut-off value was 1.52 cm, which resulted in a sensitivity of 75.0%, a specificity of 86.7%, a positive predictive value of 84.6% and a negative predictive value of 77.8%. CONCLUSIONS: The TAPSE is inversely correlated with the CVP in mechanically ventilated critically ill patients who have a LVEF less than 55%.

SIRT6 facilitates directional telomere movement upon oxidative damage.

Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly understood. Here, we show that oxidative damage at telomeres triggers directional telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is required for oxidative damage-induced telomeric movement. SIRT6 knock out (KO) cells show neither damage-induced telomere movement nor chromatin decondensation at damaged telomeres; both are observed in wild type (WT) cells. A deacetylation mutant of SIRT6 increases damage-induced telomeric movement in SIRT6 KO cells as well as WT SIRT6. SIRT6 recruits the chromatin-remodeling protein SNF2H to damaged telomeres, which appears to promote chromatin decondensation independent of its deacetylase activity. Together, our results suggest that SIRT6 plays a role in the regulation of telomere movement upon oxidative damage, shedding new light onto the function of SIRT6 in telomere maintenance.

Outcomes and risk factors of patients with acute fatty liver of pregnancy: a multicentre retrospective study.

INTRODUCTION: Acute fatty liver of pregnancy (AFLP) frequently causes liver failure in pregnant women. A better understanding of the clinical characteristics, management, outcomes and risk factors of AFLP is required, given its relatively high mortality rate. We aimed to describe the characteristics of AFLP, and further assess its outcomes and potential risk factors from the perspectives of the mother and fetus. METHODS: This was a retrospective cohort study of 133 patients with AFLP hospitalised at four tertiary hospitals in China between January 2009 and April 2014. RESULTS: Among 133 patients, AFLP was diagnosed in the postpartum period for 13 (9.8%) patients. Potential factors influencing adverse maternal outcome were male fetus (p = 0.04), postpartum diagnosis of AFLP (p < 0.01), intrauterine fetal death (p = 0.04), disseminated intravascular coagulation (p < 0.01), prothrombin time (p < 0.01) and activated partial thromboplastin time (p = 0.04). The frequency of fetal distress (p = 0.03) and activated partial thromboplastin time (p < 0.05) were significantly higher in pregnancies with dead fetuses than in those where the fetuses survived. Independent risk factors for perinatal maternal mortality were history of legal termination of pregnancy (odds ratio [OR] 1.958, 95% confidence interval [CI] 1.133-3.385), total bilirubin (OR 1.009, 95% CI 1.003-1.014) and serum creatinine (OR 1.010, 95% CI 1.003-1.017). CONCLUSION: Compared with total bilirubin and serum creatinine, history of legal termination of pregnancy appeared to be a greater risk factor for maternal mortality among patients with AFLP.

Different effects of cardiac and diaphragm function assessed by ultrasound on extubation outcomes in difficult-to-wean patients: a cohort study.

BACKGROUND: Ultrasound is a convenient tool to evaluate cardiac and diaphragm function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed in predicting extubation outcomes independently, however their different roles in the weaning process have not been determined until now. METHODS: We designed a cohort study to preform diaphragm ultrasound and TTE before and after the spontaneous breathing trial (SBT) in difficult-to-wean patients. Patients considered for enrollment should succeed on a SBT and have been extubated. They were followed up with the events of respiratory failure within 48 h, and divided into the respiratory failure and extubation success subgroups. Relevant risk factors predicting respiratory failure were analysed by a multivariate logistic regression model. Then, each subgroup was assessed with respect to re-intubation within 1 week, and divided into the re-intubation and non-intubation subgroups. Furthermore, relevant risk factors predicting re-intubation were also analysed in each subgroup. The area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic curve. RESULTS: Among 60 patients, 29 cases developed respiratory failure within 48 h, and 14 cases were re-intubated or died within 1 week, respectively. Multivariate logistic regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular ejection fraction were associated with respiratory failure. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥ 12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively. Furthermore, in the respiratory failure subgroup only DE (average) after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P = 0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively. CONCLUSIONS: E/Ea (average) after SBT could help predict respiratory failure within 48 h. However, DE (average) after SBT could help predict re-intubation within 1 week in the respiratory failure subgroup.