Machine-learning-aided decision-making model for the discontinuation of continuous renal replacement therapy.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a primary form of renal support for patients with acute kidney injury in an intensive care unit. Making an accurate decision of discontinuation is crucial for the prognosis of patients. Previous research has mostly focused on the univariate and multivariate analysis of factors in CRRT, without the capacity to capture the complexity of the decision-making process. The present study thus developed a dynamic, interpretable decision model for CRRT discontinuation. METHODS: The study adopted a cohort of 1234 adult patients admitted to an intensive care unit in the MIMIC-IV database. We used the extreme gradient boosting (XGBoost) machine learning algorithm to construct dynamic discontinuation decision models across four time points. Shapley additive explanation (SHAP) analysis was conducted to show the contribution of an individual feature to the model output. RESULTS: Of the 1234 included patients with CRRT, 596 (48.3%) successfully discontinued CRRT. The dynamic prediction by the XGBoost model produced an area under the curve of 0.848 and accuracy, sensitivity, and specificity of 0.782, 0.786, and 0.776, respectively. The XGBoost model was thus far superior to other test models. SHAP demonstrated that the features that contributed most to the model results were the sequential organ failure assessment score, serum lactate level, and 24-hour urine output. CONCLUSIONS: Dynamic decision models supported by machine learning are capable of dealing with complex factors in CRRT and effectively predicting the outcome of discontinuation.

Efficacy and Safety of Glucocorticoid in the Treatment of Acute Respiratory Distress Syndrome caused by Covid-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of glucocorticoids in the treatment of ARDS caused by COVID-19 are still controversial; therefore, we conducted this meta-analysis of the literature on this topic. METHODS: Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from the establishment of the databases to August 16, 2023. Randomized controlled trials (RCTs) and cohort studies that compared glucocorticoid versus standard treatment for ARDS caused by COVID-19 were included. The Newcastle-Ottawa Scale (NOS) checklist and the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias. Review Manager 5.4 software and STATA 17.0 were used for meta-analy-sis, and the relative risk (RR), mean difference, and 95% confidence intervals (CIs) were then determined. Results: A total of 17 studies involving 8592 patients were evaluated, including 14 retrospective studies and 3 RCTs. Sixteen studies reported data on all-cause mortality. The results of the meta-analysis showed that glucocorticoids did not reduce all-cause (RR, 0.96; 95% CI 0.82-1.13, P = .62) or 28-day (RR, 1.01; 95% CI 0.78-1.32, P = .93) mortality. Subgroup analysis showed that only methylprednisolone reduced all-cause mortality. No matter whether glucocorticoid use was early or delayed, high-dose or low-dose, long-term or short-term, no regimen reduced all-cause mortality. Furthermore, there were no significant differences in length of intensive care unit (ICU) stay, length of hospital stay, hyperglycemia, and ventilator-associated pneumonia (VAP); how-ever, glucocorticoids increased the number of ventilator-free days. CONCLUSIONS: Although methylprednisolone may reduce all-cause mortality from ARDS caused by COVID-19, this effect was not found with other types of glucocorticoids. At the same time, glucocorticoid use was associ-ated with more ventilator-free days, without increasing the incidence of hyperglycemic events or VAP. Con-sidering that almost all of the included studies were retrospective cohort studies, more RCTs are needed to confirm these findings.

Chinese critical care certified course in intensive care unit: a nationwide-based analysis.

BACKGROUND: A training program for intensive care unit (ICU) physicians entitled "Chinese Critical Care Certified Course" (5 C) started in China in 2009, intending to improve the quality of intensive care provision. This study aimed to explore the associations between the 5 C certification of physicians and the quality of intensive care provision in China. METHODS: This nationwide analysis collected data regarding 5 C-certified physicians between 2009 and 2019. Fifteen ICU quality control indicators (three structural, four procedural, and eight outcome-based) were collected from the Chinese National Report on the Services, Quality, and Safety in Medical Care System. Provinces were stratified into three groups based on the cumulative number of 5 C certified physicians per million population. RESULTS: A total of 20,985 (80.41%) physicians from 3,425 public hospitals in 30 Chinese provinces were 5 C certified. The deep vein thrombosis (DVT) prophylaxis rate in the high 5 C physician-number provinces was significantly higher than in the intermediate 5 C physician-number provinces (67.6% vs. 55.1%, p = 0.043), while ventilator-associated pneumonia (VAP) rate in the low 5 C physician-number provinces was significantly higher than in the high 5 C physician-number provinces (14.9% vs. 8.9%, p = 0.031). CONCLUSIONS: The higher number of 5 C-certified physicians per million population seemed to be associated with higher DVT prophylaxis rates and lower VAP rates in China, suggesting that the 5 C program might have a beneficial impact on the quality of intensive care provision.

The risk factors for deep venous thrombosis in critically ill older adult patients: a subgroup analysis of a prospective, multicenter, observational study.

BACKGROUND: Older adult patients mainly suffer from multiple comorbidities and are at a higher risk of deep venous thrombosis (DVT) during their stay in the intensive care unit (ICU) than younger adult patients. This study aimed to analyze the risk factors for DVT in critically ill older adult patients. METHODS: This was a subgroup analysis of a prospective, multicenter, observational study of patients who were admitted to the ICU of 54 hospitals in Zhejiang Province from September 2019 to January 2020 (ChiCTR1900024956). Patients aged > 60 years old on ICU admission were included. The primary outcome was DVT during the ICU stay. The secondary outcomes were the 28- and 60-day survival rates, duration of stay in ICU, length of hospitalization, pulmonary embolism, incidence of bleeding events, and 60-day coagulopathy. RESULTS: A total of 650 patients were finally included. DVT occurred in 44 (2.3%) patients. The multivariable logistic regression analysis showed that age (≥75 vs 60-74 years old, odds ratio (OR) = 2.091, 95% confidence interval (CI): 1.308-2.846, P = 0.001), the use of analgesic/sedative/muscarinic drugs (OR = 2.451, 95%CI: 1.814-7.385, P = 0.011), D-dimer level (OR = 1.937, 95%CI: 1.511-3.063, P = 0.006), high Caprini risk score (OR = 2.862, 95%CI: 1.321-2.318, P = 0.039), basic prophylaxis (OR = 0.111, 95%CI: 0.029-0.430, P = 0.001), and physical prophylaxis (OR = 0.322, 95%CI: 0.109-0.954, P = 0.041) were independently associated with DVT. There were no significant differences in 28- and 60-day survival rates, duration of stay in ICU, total length of hospitalization, 60-day pulmonary embolism, and coagulation dysfunction between the two groups, while the DVT group had a higher incidence of bleeding events (2.6% vs. 8.9%, P < 0.001). CONCLUSION: In critically ill older adult patients, basic prophylaxis and physical prophylaxis were found as independent protective factors for DVT. Age (≥75 years old), the use of analgesic/sedative/muscarinic drugs, D-dimer level, and high Caprini risk score were noted as independent risk factors for DVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024956).URL: http://www.chictr.org.cn/listbycreater.aspx .

Diaphragmatic ultrasonography-based rapid shallow breathing index for predicting weaning outcome during a pressure support ventilation spontaneous breathing trial.

BACKGROUND: The optimum timing to wean is crucial to avoid negative outcomes for mechanically ventilated patients. The rapid shallow breathing index (RSBI), a widely used weaning index, has limitations in predicting weaning outcomes. By replacing the tidal volume of the RSBI with diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) assessed by ultrasonography, we calculated two weaning indices, the diaphragmatic excursion rapid shallow breathing index (DE-RSBI, respiratory rate [RR]/DE) and the diaphragm thickening fraction rapid shallow breathing index (DTF-RSBI, RR/DTF). The aim of this study was to evaluate the predictive values of DTF-RSBI, DE-RSBI and traditional RSBI in weaning failure. METHODS: This prospective observational study included patients undergoing mechanical ventilation (MV) for > 48 h and who were readied for weaning. During a pressure support ventilation (PSV) spontaneous breathing trial (SBT), right hemidiaphragmatic excursion and DTF were measured by bedside ultrasonography as well as RSBI. Weaning failure was defined as: (1) failing the SBT and (2) SBT success but inability to maintain spontaneous breathing for more than 48 h without noninvasive or invasive ventilation. A receiver operator characteristic (ROC) curve was used for analyzing the diagnostic accuracy of RSBI, DE-RSBI, and DTF-RSBI. RESULTS: Of the 110 patients studied, 37 patients (33.6%) failed weaning. The area under the ROC (AUROC) curves for RSBI, DE-RSBI, and DTF-RSBI for predicting failed weaning were 0.639, 0.813, and 0.859, respectively. The AUROC curves for DE-RSBI and DTF-RSBI were significantly higher than for RSBI (P = 0.004 and P < 0.001, respectively). The best cut-off values for predicting failed weaning were RSBI > 51.2 breaths/min/L, DE-RSBI > 1.38 breaths/min/mm, and DTF-RSBI > 78.1 breaths/min/%. CONCLUSIONS: In this study, two weaning indices determined by bedside ultrasonography, the DE-RSBI (RR/DE) and DTF-RSBI (RR/DTF), were shown to be more accurate than the traditional RSBI (RR/VT) in predicting weaning outcome during a PSV SBT.

Transcutaneous oxygen pressure-related variables as noninvasive indicators of low lactate clearance in sepsis patients after resuscitation.

The transcutaneous oxygen challenge test (OCT) is associated with central venous oxygen saturation and cardiac output index, and has predictive value for prognosis. Whether the change of transcutaneous oxygen pressure (PtcO2)-related variables can reflect lactate clearance in sepsis patients is worth studying. We conducted a prospective observational study of 79 patients with sepsis or septic shock in the ICU. Immediately after enrollment, PtcO2 monitoring was continuously performed for 6 h. The OCT was performed at enrollment (T0) and the sixth hour (T6). The correlation between lactate clearance and PtcO2-related variables such as PtcO2 at T6, ΔPtcO2 (PtcO2 at T6 - PtcO2 at T0), ΔPtcO2 index (PtcO2/PaO2 at T6 - PtcO2/PaO2 at T0), 10 OCT [(PtcO2 after 10 min on FiO2 of 1.0) - (PtcO2 at baseline)], Δ10 OCT (10 OCT at T6 - 10 OCT at T0) was analyzed. The difference of PtcO2-related variables was compared between the high and low lactate clearance groups. PtcO2 at T6 (r = 0.477, p < 0.001), ΔPtcO2 (r = 0.592, p < 0.001), ΔPtcO2 index (r = 0.553, p < 0.001) and Δ10 OCT (r = 0.379, p = 0.001) were significantly correlated with the lactate clearance. To discriminate low lactate clearance, the area under the ROC curve was largest for ΔPtcO2, which was 0.804. PtcO2 at T6, PtcO2 index, ΔPtcO2, ΔPtcO2 index and Δ10 OCT were significantly different between the two different lactate clearance groups. Low lactate clearance in the initial 6 h of resuscitation of septic shock was associated to lower improvements in PtcO2-related variables.

A Comparison of Clinical Characteristics and Outcomes in Elderly and Younger Patients with COVID-19.

BACKGROUND The aim of this study was to describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and compare these parameters in an elderly group with those in a younger group. MATERIAL AND METHODS This retrospective, single-center observational study included 69 hospitalized patients with laboratory-confirmed COVID-19 from a tertiary hospital in Wuhan, China, between January 14, 2020, and February 26, 2020. Epidemiological, demographic, clinical, and laboratory data, as well as treatments, complications, and outcomes were extracted from electronic medical records and compared between elderly patients (aged ≥60 years) and younger patients (aged <60 years). Patients were followed until March 19, 2020. RESULTS Elderly patients had more complications than younger patients, including acute respiratory distress syndrome (ARDS; 9/25, 36% vs. 5/44, 11.4%) and cardiac injury (7/25, 28% vs. 1/44, 2.3%), and they were more likely to be admitted to the intensive care unit (6/25, 24% vs. 2/44, 4.5%). As of March 19, 2020, 60/69 (87%) of the patients had been discharged, 6/69 (8.7%) had died, and 3/69 (4.3%) remained in the hospital. Of those who were discharged or died, the median duration of hospitalization was 13.5 days (interquartile range, 10-18 days). CONCLUSIONS Elderly patients with confirmed COVID-19 were more likely to develop ARDS and cardiac injury than younger patients and were more likely to be admitted to the intensive care unit. In addition to routine monitoring and respiratory support, cardiac monitoring and supportive care should be a focus in elderly patients with COVID-19.

Interaction between low tidal volume ventilation strategy and severity of acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Although low tidal volume is strongly recommended for acute respiratory distress syndrome (ARDS), whether or not the benefit varies according to the severity of ARDS remains unclear. This study aimed to investigate whether or not there is an interaction between low tidal volume and severity of ARDS. METHODS: This was a secondary analysis from a randomized controlled trial. The patients were subgrouped according to whether the PaO2/FiO2 (P/F) was > 150 or ≤ 150 mmHg on day 0. The interaction between a tidal volume of 6 mL/kg and the P/F was investigated in hierarchical chi-square analysis and logistic regression models. RESULTS: Eight hundred and thirty-six patients with ARDS were enrolled (345 in the high P/F subgroup [> 150 mmHg] and 491 in the low P/F subgroup [≤ 150 mmHg]). Compared to the traditional tidal volume group, the mortality of patients with low tidal volume was significantly lower in the high P/F subgroup (41/183 (22.4%) vs. 64/162 (39.5%), p = 0.001) but not in the low P/F subgroup (95/256 (37.1%) vs. 96/235 (40.8%), p = 0.414). In the hierarchical chi-square analysis, the test of homogeneity was significant (risk ratio of mortality 0.56 [0.40-0.79] vs. 0.91 [0.73-1.13], p = 0.018). In the multivariable logistic model, the odds ratio of mortality for the interacted item was significant (2.02, 95% confidence interval [CI] 1.06-3.86, p = 0.033). The odds ratio of mortality for low tidal volume was significant in the high P/F subgroup (0.42, 95% CI 0.24-0.72, p = 0.002) but not in the low P/F subgroup (0.89, 95% CI 0.60-1.31, p = 0.554). CONCLUSIONS: The benefits of low tidal volume ventilation remain uncertain in patients with severe ARDS. Further studies are needed to validate this significant interaction.

Perioperative Fluid Restriction in Abdominal Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Perioperative fluid management is a critical component in patients undergoing abdominal surgery. However, the benefit of restricted fluid regimen remains inconclusive. This systematic review aimed to explore potential factors causing these inconsistent findings. METHODS: The literature searches were performed in three databases including PubMed, Embase, and the Cochrane library until August 30, 2018. Only randomized, controlled trials comparing the effect of restricted versus liberal regimen in abdominal surgery were included. The primary outcome was total postoperative complications. Subgroup analysis was performed according to between-group weight increase difference (≥ 2 kg and < 2 kg) and fluid intake ratio (≥ 1.8 and < 1.8). RESULTS: Sixteen studies were finally included in this meta-analysis. The benefit of the restricted regimen in reducing postoperative complication was only significant in the subgroup with high weight increase difference (≥ 2 kg) (RR 0.67, 95% CI 0.57-0.79) and the subgroup with high fluid intake ratio (≥ 1.8) (RR 0.72, 95% CI 0.62-0.82). In the subgroup with low weight increase difference (< 2 kg) or low fluid intake ratio (< 1.8), the effect of the restricted regimen was not significant (RR 0.88, 95% CI 0.51-1.50, and RR 1.18, 95% CI 0.91-1.53, respectively). CONCLUSIONS: The benefit of the restricted regimen was only significant in the subgroup with high weight increase difference (≥ 2 kg) or high fluid intake ratio (≥ 1.8).

Persistent hyperlactatemia-high central venous-arterial carbon dioxide to arterial-venous oxygen content ratio is associated with poor outcomes in early resuscitation of septic shock.

OBJECTIVE: Several studies reported Pv-aCO2/Ca-vO2 ratio as a surrogate of VCO2/VO2 to detect global tissue hypoxia. The present study aimed to evaluate the prognostic value of Pv-aCO2/Ca-vO2 ratio combined with lactate levels during the early phases of resuscitation in septic shock. METHODS: A retrospective study was conducted in 144 septic shock patients in a 30-bed mixed ICU. A Pv-aCO2/Ca-vO2 ratio>1.4 was considered abnormal. Patients were classified into four predefined groups according to lactate levels and Pv-aCO2/Ca-vO2 ratio after the first 6h of resuscitation. Sequential Organ Failure Assessment (SOFA) score at day 3 was assessed. A Kaplan-Meier curve showed the survival probabilities at day 28 using a log-rank test to evaluate the differences between groups. A receiver operating characteristics (ROC) curve evaluated the ability of lactate, Pv-aCO2/Ca-vO2 ratio and Pv-aCO2/Ca-vO2 ratio combined with lactate to predict mortality at day 28. RESULTS: Combination of hyperlactatemia and high Pv-aCO2/Ca-vO2 ratio was associated with poor SOFA scores and low survival rates at day 28 (P<0.001). The Cox multivariate survival analysis demonstrated that Pv-aCO2/Ca-vO2 ratio and lactate at T6 were independent predictors of mortality at day 28. The area under the ROC curve of the Pv-aCO2/Ca-vO2 ratio combined with lactate for predicting mortality at day 28 was highest and superior to that of lactate and Pv-aCO2/Ca-vO2 ratios. CONCLUSION: Combination of Pv-aCO2/Ca-vO2 ratio and lactate at early stages of resuscitation of septic shock can better predict the prognosis of patients. The Pv-aCO2/Ca-vO2 ratio may become a useful parameter supplementary to lactate in the resuscitation of septic shock.

ß3-integrin inhibits lipopolysaccharide-induced autophagy in cardiomyocytes via the Akt signaling pathway.

OBJECTIVE: To investigate the role of ß 3 -integrin in lipopolysaccharide (LPS)-induced autophagy in cardiomyocytes and its underlying mechanism. METHODS: ß 3 -Integrin expression in cardiomyocytes was up- or downregulated by adenovirus transfection or cyclic arginine-glycine-aspartic acid (cRGD) peptide treatment before LPS stimulation. The expression of autophagy-associated proteins (LC3-II, Beclin-1 and Bcl-2) and the activation of Akt were determined using Western blotting. Autophagosomes and autophagic vacuoles were observed using monodansylcadaverine (MDC) dye and transmission electron microscopy, respectively. RESULTS: Downregulation of ß 3 -integrin with cRGD peptide resulted in enhanced LC3-II and Beclin-1 and decreased Bcl-2 expression. Low Beclin-1 levels were detected after LPS stimulation in adenovirus ß 3 -integrin-transfected cardiomyocytes. There was no significant difference in LC3-II levels between control and adenovirus ß 3 -integrin-transfected cardiomyocytes. Enhanced accumulation of MDC dye and autophagosomes, which were inhibited by ß 3 -integrin overexpression, were detected after LPS treatment. The increased phosphorylation of Akt after LPS stimulation was inhibited by cRGD and enhanced by ß 3 -integrin overexpression. Furthermore, the Akt inhibitor triciribine inhibited the negative effect of ß 3 - integrin on autophagy, as shown by LC3-II and Beclin-1 upregulation. CONCLUSIONS: ß 3 -Integrin inhibits LPS-induced autophagy in cardiomyocytes. The inhibition of Akt signaling might be an important mechanism in this process.

Combined cardiac, lung, and diaphragm ultrasound for predicting weaning failure during spontaneous breathing trial.

BACKGROUND: Weaning from invasive mechanical ventilation (MV) is a complex and challenging process that involves multiple pathophysiological mechanisms. A combined ultrasound evaluation of the heart, lungs, and diaphragm during the weaning phase can help to identify risk factors and underlying mechanisms for weaning failure. This study aimed to investigate the accuracy of lung ultrasound (LUS), transthoracic echocardiography (TTE), and diaphragm ultrasound for predicting weaning failure in critically ill patients. METHODS: Patients undergoing invasive MV for > 48 h and who were readied for their first spontaneous breathing trial (SBT) were studied. Patients were scheduled for a 2-h SBT using low-level pressure support ventilation. LUS and TTE were performed prospectively before and 30 min after starting the SBT, and diaphragm ultrasound was only performed 30 min after starting the SBT. Weaning failure was defined as failure of SBT, re-intubation, or non-invasive ventilation within 48 h. RESULTS: Fifty-one patients were included, of whom 15 experienced weaning failure. During the SBT, the global, anterior, and antero-lateral LUS scores were higher in the failed group than in the successful group. Receiver operating characteristic curve analysis showed that the areas under the curves for diaphragm thickening fraction (DTF) and global and antero-lateral LUS scores during the SBT to predict weaning failure were 0.678, 0.719, and 0.721, respectively. There was no correlation between the LUS scores and the average E/e' ratio during the SBT. Multivariate analysis identified antero-lateral LUS score > 7 and DTF < 31% during the SBT as independent predictors of weaning failure. CONCLUSION: LUS and diaphragm ultrasound can help to predict weaning failure in patients undergoing an SBT with low-level pressure support. An antero-lateral LUS score > 7 and DTF < 31% during the SBT were associated with weaning failure.

[A correlation study between body mass index and exercise capacity in patients with chronic systolic heart failure].

OBJECTIVE: To investigate the association between body mass index (BMI) and exercise capacity in patients with chronic systolic heart failure. METHODS: The elderly patients with chronic systolic heart failure were consecutively recruited from 2008 to 2011 in cardiovascular clinic of Zhejiang Hospital. All the participants underwent height and weight measurements and BMI was calculated with these two parameters. Cardiopulmonary exercise test were performed to achieve peak oxygen uptake (PVO(2)), oxygen uptake to body mass ratio (PKVO(2)), oxygen uptake to heart ratio (VO(2)/HR) and ventilation/carbon dioxide production (VO(2)/VCO(2)). RESULTS: A total of the 273 patients with chronic systolic heart failure included 6 underweight patients (BMI < 18.5 kg/m(2)), 113 normal weight patients (BMI 18.5 - < 24.0 kg/m(2)), 116 overweight patients (BMI 24.0 - < 28.0 kg/m(2)), and 38 obese patients (BMI ≥ 28 kg/m(2)). In both NYHA II and III/IV patients, unadjusted correlation analyses showed that BMI was positively related to PVO(2) and VO(2)/HR, and was inversely related to PKVO(2) and VE/VCO(2) (P < 0.05), respectively. Multiple stepwise regression analyses showed age, sex, BMI (P < 0.05) and left ventricular ejection fraction (LVEF) were independent determinants of PKVO(2), and age and BMI (P < 0.05) were independent determinants of VE/VCO(2). CONCLUSIONS: BMI is significantly associated with exercise capacity in patients with chronic systolic heart failure, and also independent determinant for the PKVO(2) and VE/VCO(2), respectively.

Increased 28-day mortality due to fluid overload prior to continuous renal replacement in sepsis associated acute kidney injury.

Patients with sepsis are prone to fluid overload (FO) due to fluid resuscitation, irrespective of stage of acute kidney injury (AKI). The aim of our study was to analyze the association between FO at continuous renal replacement therapy (CRRT) initiation and 28-day mortality in patients with sepsis associated AKI (S-AKI). In this retrospective study, data for patient characteristics were collected and 28-day mortality were studied. We also analyze association of variables, including FO degrees with 28-day mortality. Earlier commencement of CRRT showed better outcome. Non-survivors had higher FO than survivor (9.17% vs. 5.20%; p = 0.016). Survival in patients with FO > 10% over 28 days was significantly worse compared to those with FO ≤ 10% (p = 0.006). Multivariate analysis showed, FO > 10% (95%CI [1.721, 17.195], p = 0.004) was significantly associated with increased 28-day mortality. In S-AKI requiring CRRT, FO > 10% at CRRT initiation was independently associated with 28-day mortality.

Homocysteine-induced caspase-3 activation by endoplasmic reticulum stress in endothelial progenitor cells from patients with coronary heart disease and healthy donors.

Previous studies have suggested an association of hyperhomocysteinemia-induced vascular pathology with enhanced apoptotic potential of endothelial progenitor cells in patients with coronary heart disease. Our results indicate that 500 µmol/L homocysteine induced endothelial progenitor cell apoptosis and activation of caspase-3, both of which were abolished by 100 µmol/L and 200 µmol/L salubrinal, an agent that prevents endoplasmic reticulum stress-induced apoptosis. The addition of 500 µmol/L homocysteine caused a release of Ca(2+) from intracellular stores, and enhanced phosphor-eukaryotic initiation factor 2α phosphorylation at Ser51 and the expression of a glucose-regulated protein of 78 kDa and a C/EBP homologous protein independently of extracellular Ca(2+). These effects of homocysteine on endothelial progenitor cells were significantly greater in patients with coronary heart disease than in healthy donors. These findings suggest that homocysteine induces endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial progenitor cells, an event that is enhanced in patients with coronary heart disease. Furthermore, enhanced endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial progenitor cells might be involved in hyperhomocysteinemia-associated vascular pathology.

[Research on high-order Windkessel model for assessing vascular compliance].

In this paper, we propose the construction of a fifth-order Windkessel model, and give complete mathematical solutions for this model. Utilizing the diastolic pulse wave analytical methods, we derived the parameters of the mathematical model. The parameters were further applied to estimate arterial compliance, blood flow inertia, peripheral resistance and other indices. With simulation tools we assess the validity of the model, and built a simulation circuit with the model parameters R, C and L. The model parameters were obtained from the high-order Windkessel model. The stroke volume of left ventricle is employed as the input of the simulation circuit. At the end of the circuit, the responding signal was gained. And it in turn was compared with the measured pulse waveform. The results show that the fifth-order Windkessel model is superior to the third-order Windkessel model in the pulse wave fitting and stability, and thus better reflects the role of microvessles in the circulatory system.

Misplacement of a central venous catheter into azygos vein via the right internal jugular vein.

For critically ill patients, central venous catheterization may not always be placed in a correct tip position, even when guided by ultrasound. A case of inadvertent catheterization into azygos vein is described.

Efficacy of airway pressure release ventilation for acute respiratory distress syndrome: a systematic review with meta-analysis.

BACKGROUND: For many years, airway pressure release ventilation (APRV) has been used to manage patients with lung conditions such as acute respiratory distress syndrome (ARDS). However, it is still unclear whether APRV improves outcomes in critically ill ARDS patients who have been admitted to an intensive care unit (ICU). METHODS: In this study, randomized controlled trials (RCTs) were used to compare the efficacy of APRV to traditional modes of mechanical ventilation. RCTs were sourced from PubMed, Cochrane, and Embase databases (the last dates from August 8, 2019). The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. The relative risk (RR), mean difference (MD), and 95% confidence intervals (CI) were then determined. Article types such as observational studies, case reports, animal studies, etc., were excluded from our meta-analysis. In total, the data of 6 RCTs and 360 ARDS patients were examined. RESULTS: Six studies with 360 patients were included, our meta-analysis showed that the mean arterial pressure (MAP) in the APRV group was higher than that in the traditional mechanical ventilation group (MD =2.35, 95% CI: 1.05-3.64, P=0.0004). The peak pressure (Ppeak) was also lower in the APRV group with a statistical difference noted (MD =-2.04, 95% CI: -3.33 to -0.75, P=0.002). Despite this, no significant beneficial effect on the oxygen index (PaO2/FiO2) was shown between the two groups (MD =26.24, 95% CI: -26.50 to 78.97, P=0.33). Compared with conventional mechanical ventilation, APRV significantly improved 28-day mortality (RR =0.66, 95% CI: 0.47-0.94, P=0.02). DISCUSSION: All the included studies were considered to have an unclear risk of bias. We determined that for critically ill patients with ARDS, the application of APRV is associated with an increase in MAP. Inversely, a reduction of the airway Ppeak and 28-day mortality was recorded. There was no sufficient evidence to support the idea that APRV is superior to conventional mechanical ventilation in improving PaO2/FiO2.

Association Between Oxygen Partial Pressure Trajectories and Short-Term Outcomes in Patients With Hemorrhagic Brain Injury.

Objectives: Arterial hyperoxia is reportedly a risk factor for poor outcomes in patients with hemorrhagic brain injury (HBI). However, most previous studies have only evaluated the effects of hyperoxia using static oxygen partial pressure (PaO2) values. This study aimed to investigate the association between overall dynamic oxygenation status and HBI outcomes, using longitudinal PaO2 data. Methods: Data were extracted from the Medical Information Mart for Intensive Care III database. Longitudinal PaO2 data obtained within 72 h of admission to an intensive care unit were analyzed, using a group-based trajectory approach. In-hospital mortality was used as the primary outcomes. Multivariable logistic models were used to explore the association between PaO2 trajectory and outcomes. Results: Data of 2,028 patients with HBI were analyzed. Three PaO2 trajectory types were identified: Traj-1 (mild hyperoxia), Traj-2 (transient severe hyperoxia), and Traj-3 (persistent severe hyperoxia). The initial and maximum PaO2 of patients with Traj-2 and Traj-3 were similar and significantly higher than those of patients with Traj-1. However, PaO2 in patients with Traj-2 decreased more rapidly than in patients with Traj-3. The crude in-hospital mortality was the lowest for patients with Traj-1 and highest for patients with Traj-3 (365/1,303, 209/640, and 43/85 for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001), and the mean Glasgow Coma Scale score at discharge (GCSdis) was highest for patients with Traj-1 and lowest in patients with Traj-3 (13 [7-15], 11 [6-15], and 7 [3-14] for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001). The multivariable model revealed that the risk of death was higher in patients with Traj-3 than in patients with Traj-1 (odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9-5.8) but similar for patients with Traj-1 and Traj-2. Similarly, the logistic analysis indicated the worst neurological outcomes in patients with Traj-3 (OR: 3.6, 95% CI: 2.0-6.4, relative to Traj-1), but similar neurological outcomes for patients in Traj-1 and Traj-2. Conclusion: Persistent, but not transient severe arterial hyperoxia, was associated with poor outcome in patients with HBI.