Effect of a self-developed fixation device on preventing endotracheal intubation-related pressure injury: a randomised controlled trial.

OBJECTIVE: To evaluate the effects of our self-developed endotracheal tube fixation device in mechanically ventilated patients. METHODS: In a dual-centre randomised controlled trial, patients who were expected to require mechanical ventilation for over 48 h were assigned to the observation group (using self-developed device) or the control group (using the traditional device). The primary endpoint was the incidence of endotracheal intubation-related pressure injury (EIRPI). RESULTS: Fifty-one patients in the observation group and 54 patients in the control group were analysed. The incidence of EIRPI was 7.8% in the observation group and 33.3% in the control group (p = 0.001). Lip pressure injury (PI) occurred in 0 versus 14 (25.9%) patients in the observation versus control groups (p < 0.001). Both oral-mucosal and facial PIs were similar between the two groups. CONCLUSIONS: The use of the novel device reduced the incidence of EIRPI, especially lip PI. Trial registration Chinese Clinical Trial Registry ChiCTR2300078132. Registered on 29 November 2023.

Development and validation of a deep interpretable network for continuous acute kidney injury prediction in critically ill patients.

Early detection of acute kidney injury (AKI) may provide a crucial window of opportunity to prevent further injury, which helps improve clinical outcomes. This study aimed to develop a deep interpretable network for continuously predicting the 24-hour AKI risk in real-time and evaluate its performance internally and externally in critically ill patients. A total of 21,163 patients' electronic health records sourced from Beth Israel Deaconess Medical Center (BIDMC) were first included in building the model. Two external validation populations included 3025 patients from the Philips eICU Research Institute and 2625 patients from Zhongda Hospital Southeast University. A total of 152 intelligently engineered predictors were extracted on an hourly basis. The prediction model referred to as DeepAKI was designed with the basic framework of squeeze-and-excitation networks with dilated causal convolution embedded. The integrated gradients method was utilized to explain the prediction model. When performed on the internal validation set (3175 [15 %] patients from BIDMC) and the two external validation sets, DeepAKI obtained the area under the curve of 0.799 (95 % CI 0.791-0.806), 0.763 (95 % CI 0.755-0.771) and 0.676 (95 % CI 0.668-0.684) for continuousAKI prediction, respectively. For model interpretability, clinically relevant important variables contributing to the model prediction were informed, and individual explanations along the timeline were explored to show how AKI risk arose. The potential threats to generalisability in deep learning-based models when deployed across health systems in real-world settings were analyzed.

Evaluation of CO2 removal rate of ECCO2 R for a renal replacement therapy platform in an experimental setting.

BACKGROUND: A critical parameter of extracorporeal CO2 removal (ECCO2 R) applications is the CO2 removal rate (VCO2 ). Low-flow venovenous extracorporeal support with large-size membrane lung remains undefined. This study aimed to evaluate the VCO2 of a low-flow ECCO2 R with large-size membrane lung using a renal replacement therapy platform in an experimental animal model. METHODS: Twelve healthy pigs were placed under mechanical ventilation and connected to an ECCO2 R-CRRT system (surface area = 1.8 m2 ; OMNIset®, BBraun, Germany). Respiratory settings were reduced to induce two degrees of hypercapnia. VCO2 was recorded under different combinations of PaCO2 (50-69 or 70-89 mm Hg), extracorporeal blood flow (ECBF; 200 or 350 mL/min), and gas flow (4, 6, or 10 L/min). RESULTS: VCO2 increased with ECBF at all three gas flow rates. In severe hypercapnia, the increase in sweep gas flow from 4 to 10 L/min increased VCO2 from 86.38 ± 7.08 to 96.50 ± 8.71 mL/min at an ECBF of 350 mL/min, whereas at ECBF of 200 mL/min, any increase was less effective. But in mild hypercapnia, the increase in sweep gas flow result in significantly increased VCO2 at two ECBF. VCO2 increased with PaCO2 from 50-69 to 70-89 mm Hg at an ECBF of 350 mL/min, but not at ECBF of 200 mL/min. Post-membrane lung PCO2 levels were similar for different levels of premembrane lung PCO2 (p = 0.08), highlighting the gas exchange diffusion efficacy of the membrane lung in gas exchange diffusion. In severe hypercapnia, the reduction of PaCO2 elevated from 11.5% to 19.6% with ECBF increase only at a high gas flow of 10 L/min (p < 0.05) and increase of gas flow significantly reduced PaCO2 only at a high ECBF of 350 mL/min (p < 0.05). CONCLUSIONS: Low-flow venovenous extracorporeal ECCO2 R-CRRT with large-size membrane lung is more efficient with the increase of ECBF, sweep gas flow rate, and the degree of hypercapnia. The influence of sweep gas flow on VCO2 depends on the ECBF and degree of hypercapnia. Higher ECBF and gas flow should be chosen to reverse severe hypercapnia.

Effects of early versus delayed application of prone position on ventilation-perfusion mismatch in patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: Prone position has been shown to improve oxygenation and survival in patients with early acute respiratory distress syndrome (ARDS). These beneficial effects are partly mediated by improved ventilation/perfusion (V/Q) distribution. Few studies have investigated the impact of early versus delayed proning on V/Q distribution in patients with ARDS. The aim of this study was to assess the regional ventilation and perfusion distribution in early versus persistent ARDS after prone position. METHODS: This is a prospective, observational study from June 30, 2021, to October 1, 2022 at the medical ICU in Zhongda Hospital, Southeast University. Fifty-seven consecutive adult patients with moderate-to-severe ARDS ventilated in supine and prone position. Electrical impedance tomography was used to study V/Q distribution in the supine position and 12 h after a prone session. RESULTS: Of the 57 patients, 33 were early ARDS (≤ 7 days) and 24 were persistent ARDS (> 7 days). Oxygenation significantly improved after proning in early ARDS (157 [121, 191] vs. 190 [164, 245] mm Hg, p < 0.001), whereas no significant change was found in persistent ARDS patients (168 [136, 232] vs.177 [155, 232] mm Hg, p = 0.10). Compared to supine position, prone reduced V/Q mismatch in early ARDS (28.7 [24.6, 35.4] vs. 22.8 [20.0, 26.8] %, p < 0.001), but increased V/Q mismatch in persistent ARDS (23.8 [19.8, 28.6] vs. 30.3 [24.5, 33.3] %, p = 0.006). In early ARDS, proning significantly reduced shunt in the dorsal region and dead space in the ventral region. In persistent ARDS, proning increased global shunt. A significant correlation was found between duration of ARDS onset to proning and the change in V/Q distribution (r = 0.54, p < 0.001). CONCLUSIONS: Prone position significantly reduced V/Q mismatch in patients with early ARDS, while it increased V/Q mismatch in persistent ARDS patients. Trial registration ClinicalTrials.gov (NCT05207267, principal investigator Ling Liu, date of registration 2021.08.20).

Impact of renal complications on outcome in adult patients with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation: an analysis of nationwide CSECLS database in China.

BACKGROUND: Limited data are available on renal complications in patients with acute fulminant myocarditis (AFM) receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in China. To evaluate the impact of renal complications on outcomes in adult patients with AFM supported with VA-ECMO. METHODS: Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Adult patients who were diagnosed with AFM receiving VA-ECMO support in the database were included. The primary outcome was 30-day mortality in patients with AFM supported with VA-ECMO. Logistic regression model was used to examine the impact of renal complications on 30-day mortality by adjusting confounders. RESULTS: A total of 202 patients were included. The median age was 38 years (IQR 29-48) and males (n = 103) represented 51.0% of the total accounted patients. The median ECMO duration was 142.9 h (IQR 112.1-188.8 h). 178 (88.1%) patients weaned from ECMO and 156 (71.9%) patients survived. 94(46.5%) patients developed renal complications while on ECMO course. Patients with renal complications had higher 30-day mortality (40.7% (37 of 94) vs 8.3% (9 of 108), P < 0.001) compared with those without. The development of renal complications was related to a 3.12-fold increase risk of 30-day mortality (adjusted OR 3.120, 95%CI 1.002-6.577, P = 0.049). Increasing age (adjusted OR1.025, 95% CI 1.008-1.298, P = 0.040) and higher SOFA score (adjusted OR 1.162, 95%CI 1.012-1.334, P = 0.034) were independent risk factors of renal complications. CONCLUSIONS: Our findings demonstrated that patients with AFM receiving VA-ECMO at high risk of developing renal complications. Advancing age and higher SOFA score was associated with increased risk of developing renal complications. The onset of renal complications was significantly associated with 30-day mortality.

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

OBJECTIVES: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). DESIGN: A multicenter, single-blind, randomized, noninferiority trial. SETTING: Twenty-one centers across China from December 2020 to June 2021. PATIENTS: A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. INTERVENTIONS: One hundred thirty-five ICU patients were randomly allocated into ciprofol ( n = 90) and propofol ( n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 µg/kg, maintenance dose: 0.02-0.15 µg/kg/min). MEASUREMENTS AND MAIN RESULTS: Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time ( p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Clinical outcome and risk factors for acute fulminant myocarditis supported by venoarterial extracorporeal membrane oxygenation: An analysis of nationwide CSECLS database in China.

BACKGROUND: To assess the outcomes and risk factors for adult patients with acute fulminant myocarditis (AFM) supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) in China mainland. METHODS: Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Data from adult patients who were diagnosed with AFM and needed VA ECMO in the database were retrospectively analyzed. The primary outcome was 90-day mortality after ECMO initiation in patients with AFM supported with VA ECMO. Cox proportional hazard regression model was used to examine the risk factors associated with 90-day mortality. RESULTS: Among 221 patients enrolled and followed up to 90 days, 186 (84.2%) patients weaned from ECMO and 159 (71.9%) patients survived and discharged home. The median age was 38 years (IQR 29-49) and males (n = 115) represented 52.0% of the total accounted patients. The median ECMO duration was 134 h (IQR 96-177 h). The main adverse event during ECMO course was bleeding (16.3%), followed by infection (15.4%). In the multivariate Cox model analysis, cardiac arrest prior to ECMO initiation (adjusted HR 2.529; 95%CI: 1.341-4.767, p = 0.004), lower pH value (adjusted HR 0.016; 95%CI: 0.010-0.059, p < 0.001) and higher lactate concentration at 24 h after ECMO initiation (adjusted HR 1.146; 95%CI: 1.075-1.221, p < 0.001) were associated with 90-day mortality. CONCLUSIONS: 71.9% patients with AFM (clinical diagnosed) supported with VA ECMO survived. Cardiac arrest prior to ECMO, lower pH and higher lactate concentration at 24 h after ECMO initiation were correlated with 90-day mortality of AFM patients supported with VA ECMO.

Longitudinal phenotypes in patients with acute respiratory distress syndrome: a multi-database study.

BACKGROUND: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) have been limited by a disregard for temporal dynamics. We aimed to identify longitudinal phenotypes in ARDS to test the prognostic and predictive enrichment of longitudinal phenotypes, and to develop simplified models for phenotype identification. METHODS: We conducted a multi-database study based on the Chinese Database in Intensive Care (CDIC) and four ARDS randomized clinical trials (RCTs). We employed latent class analysis (LCA) to identify longitudinal phenotypes using 24-hourly data from the first four days of invasive ventilation. We used the Cox regression model to explore the association between time-varying respiratory parameters and 28-day mortality across phenotypes. Phenotypes were validated in four RCTs, and the heterogeneity of treatment effect (HTE) was investigated. We also constructed two multinomial logistical regression analyses to develop the probabilistic models. FINDINGS: A total of 605 ARDS patients in CDIC were enrolled. The three-class LCA model was identified and had the optimal fit, as follows: Class 1 (n = 400, 66.1% of the cohort) was the largest phenotype over all study days, and had fewer abnormal values, less organ dysfunction and the lowest 28-day mortality rate (30.5%). Class 2 (n = 102, 16.9% of the cohort) was characterized by pulmonary mechanical dysfunction and had the highest proportion of poorly aerated lung volume, the 28-day mortality rate was 47.1%. Class 3 (n = 103, 17% of the cohort) was correlated with extra-pulmonary dysfunction and had the highest 28-day mortality rate (56.3%). Time-varying mechanical power was more significantly associated with 28-day mortality in Class 2 patients compared to other phenotypes. Similar phenotypes were identified in four RCTs. A significant HTE between phenotypes and treatment strategies was observed in the ALVEOLI (high PEEP vs. low PEEP) and the FACTT trials (conservative vs. liberal fluid management). Two parsimonious probabilistic models were constructed to identify longitudinal phenotypes. INTERPRETATION: We identified and validated three novel longitudinal phenotypes for ARDS patients, with both prognostic and predictive enrichment. The phenotypes of ARDS can be accurately identified with simple classifier models, except for Class 3.

Expression of PD-1 on Memory T Lymphocytes Predicts 28-Day Mortality of Patients with Sepsis: A Prospective Observational Study.

Background: PD-1 is an important immune checkpoint expressed on T lymphocytes and is associated with T-cell function in sepsis. However, the role of PD-1 in naive and memory T-cell responses in sepsis is not well understood. We aimed to determine the expression of PD-1 induced on naive and memory T lymphocytes in patients with sepsis and its association with clinical outcome. Methods: A prospective observational study was conducted at a general intensive care unit (ICU). Whole blood samples were collected from patients within 48 h after sepsis diagnosis. PD-1 expression on naive and memory T cells was measured by flow cytometry. The levels of IFN-γ, IL-2 and TNF-α released by memory T cells were also determined. All patients were followed up to 28 days, and 28-day mortality was recorded. Results: PD-1 expression showed no difference in naive CD4+ T cells (P=0.617) or naive CD8+ T cells (P=0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4+ T cells was found in nonsurvivors (P=0.030) and memory CD8+ T cells (P=0.006) in comparison with survivors. According to the cutoff value of the percentage of PD-1 on memory CD8+ T cells in predicting 28-day mortality of patients with sepsis, patients were divided into two groups. The 28-day mortality rates between the two groups were significantly different (P=0.009). A Kaplan Meier curve was constructed to derive a hazard ratio of 9.33 (95% CI: 2.52-34.60) for the percentage of PD-1 on memory CD8+ T cells regarding 28-day mortality. In addition, the IFN-γ secretion of memory CD4+ T cells (P=0.046) and IL-2 secretion of memory CD8+ T cells (P=0.014) were significantly greater in survivors than nonsurvivors. Conclusion: Flow cytometric assessment of PD-1 expression on memory CD8+ T cells identifies patients with poor outcomes during sepsis.

Beneficial effect of Xuebijing against Pseudomonas aeruginosa infection in Caenorhabditis elegans.

In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. Caenorhabditis elegans is an important experimental host for bacterial infections. Using C. elegans as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by Pseudomonas aeruginosa infection. For the cellular mechanisms of this antibacterial infection property, we found that Xuebijing treatment rescued C. elegans lifespan to be against P. aeruginosa infection by inhibiting Pseudomonas colonization in the intestinal lumen. Meanwhile, the increase in the expression of antimicrobial genes induced by Pseudomonas infection was also suppressed by Xuebijing treatment. Moreover, the beneficial effect of Xuebijing against Pseudomonas infection depended on insulin, p38 MAPK, Wnt, DBL-1/TGF-ß, ELT-2, and programmed cell death (PCD)-related signals. Although Xuebijing did not show obvious antibacterial activity, Xuebijing (100%) treatment could inhibit the Pseudomonas biofilm formation and decrease the expression of virulence genes (lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS) and quorum sensing (QS)-related genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR). Our results support the potential role of Xuebijing treatment against bacterial infection in hosts.

Addition of terlipressin to norepinephrine in septic shock and effect of renal perfusion: a pilot study.

PURPOSE: Terlipressin improves renal function in patients with septic shock. However, the mechanism remains unclear. Here, we aimed to evaluate the effects of terlipressin on renal perfusion in patients with septic shock. MATERIALS AND METHODS: This pilot study enrolled patients with septic shock in the intensive care unit of the tertiary hospital from September 2019 to May 2020. We randomly assigned patients to terlipressin and usual care groups using a 1:1 ratio. Terlipressin was intravenously pumped at a rate of 1.3 µg/kg/hour for 24 h. We monitored renal perfusion using renal contrast-enhanced ultrasound (CEUS). The primary outcome was peak sonographic signal intensity (a renal perfusion parameter monitored by CEUS) at 24 h after enrollment. RESULTS: 22 patients were enrolled in this study with 10 in the terlipressin group and 12 in the usual care group. The baseline characteristics of patients between the two groups were comparable. The peak sonographic signal intensity at 24 h after enrollment in the terlipressin group (60.5 ± 8.6 dB) was significantly higher than that in the usual care group (52.4 ± 7.0 dB; mean difference, 7.1 dB; 95% CI, 0.4-13.9; adjusted p = .04). Patients in the terlipressin group had a lower time to peak, heart rates, norepinephrine dose, and a higher stroke volume at 24 h after enrollment. No significant difference in the urine output within 24 h and incidence of acute kidney injury within 28 days was found between the two groups. CONCLUSIONS: Terlipressin improves renal perfusion, increases stroke volume, and decreases norepinephrine dose and heart rates in patients with septic shock.

Associations between CT pulmonary opacity score on admission and clinical characteristics and outcomes in patients with COVID-19.

This study investigated associations between chest computed tomography (CT) pulmonary opacity score on admission and clinical features and outcomes in COVID-19 patients. The retrospective multi-center cohort study included 496 COVID-19 patients in Jiangsu province, China diagnosed as of March 15, 2020. Patients were divided into four groups based on the quartile of pulmonary opacity score: ≤ 5%, 6-20%, 21-40% and 41% +. CT pulmonary opacity score was independently associated with age, single onset, fever, cough, peripheral capillary oxygen saturation, lymphocyte count, platelet count, albumin level, C-reactive protein (CRP) level and fibrinogen level on admission. Patients with score ≥ 41% had a dramatic increased risk of severe or critical illness [odds ratio (OR), 15.58, 95% confidence interval (CI) 3.82-63.53), intensive care unit (ICU)] admission (OR, 6.26, 95% CI 2.15-18.23), respiratory failure (OR, 19.49, 95% CI 4.55-83.40), and a prolonged hospital stay (coefficient, 2.59, 95% CI 0.46-4.72) compared to those with score ≤ 5%. CT pulmonary opacity score on admission, especially when ≥ 41%, was closely related to some clinical characteristics and was an independent predictor of disease severity, ICU admission, respiratory failure and long hospital stay in patients with COVID-19.

A nomogram predicting severe COVID-19 based on a large study cohort from China.

BACKGROUND: The use of accurate prediction tools and early intervention are important for addressing severe coronavirus disease 2019 (COVID-19). However, the prediction models for severe COVID-19 available to date are subject to various biases. This study aimed to construct a nomogram to provide accurate, personalized predictions of the risk of severe COVID-19. METHODS: This study was based on a large, multicenter retrospective derivation cohort and a validation cohort. The derivation cohort consisted of 496 patients from Jiangsu Province, China, between January 10, 2020, and March 15, 2020, and the validation cohort contained 105 patients from Huangshi, Hunan Province, China, between January 21, 2020, and February 29, 2020. A nomogram was developed with the selected predictors of severe COVID-19, which were identified by univariate and multivariate logistic regression analyses. We evaluated the discrimination of the nomogram with the area under the receiver operating characteristic curve (AUC) and the calibration of the nomogram with calibration plots and Hosmer-Lemeshow tests. RESULTS: Three predictors, namely, age, lymphocyte count, and pulmonary opacity score, were selected to develop the nomogram. The nomogram exhibited good discrimination (AUC 0.93, 95% confidence interval [CI] 0.90-0.96 in the derivation cohort; AUC 0.85, 95% CI 0.76-0.93 in the validation cohort) and satisfactory agreement. CONCLUSIONS: The nomogram was a reliable tool for assessing the probability of severe COVID-19 and may facilitate clinicians stratifying patients and providing early and optimal therapies.

Synbiotic Therapy Prevents Nosocomial Infection in Critically Ill Adult Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Based on a Bayesian Framework.

Background: The efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition (EPN) and total parenteral nutrition (TPN) in preventing nosocomial infection (NI) in critically ill adults has been questioned. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) to evaluate and rank the effectiveness of these therapies on NI amongst critically ill adults. Methods: Four electronic databases were systematically searched up to June 30, 2019 for RCTs comparing the administration of probiotics, prebiotics, synbiotics, EPN and TPN in critically ill adults. The primary outcome was NI. The relative efficacy of all outcomes was determined by a Bayesian framework with random effects NMA. We estimated the odds ratio (OR) and mean difference (MD) and ranked the comparative effects of all regimens with the surface under the cumulative ranking probabilities. The study has been registered on PROSPERO (CRD42019147032). Results: Fifty-five RCTs (7,119 patients) were identified. Primary outcome showed that synbiotics had the best effect in preventing NI than EPN (OR 0.37; 95% CrI 0.22-0.61), probiotics followed (OR 0.52; 95% CrI 0.34-0.77), whereas TPN significantly increased NI (OR 2.29; 95% CrI 1.48-3.67). Subgroup analysis showed that TPN significantly increased NI in intensive care unit (ICU) patients (OR 1.57; 95% CrI 1.01-2.56) and severe acute pancreatitis (SAP) patients (OR 3.93; 95% CrI 1.74-9.15). Secondary outcomes showed that synbiotics were more effective in preventing hospital-acquired pneumonia (HAP) (OR 0.34; 95% CrI 0.11-0.85), catheter-related bloodstream infection (OR 0.08; 95% CrI 0.01-0.80), urinary tract infection (OR 0.27; 95% CrI 0.08-0.71) and sepsis (OR 0.34; 95% CrI 0.16-0.70) than EPN. Amongst the treatments, probiotics were most effective for shortening the mechanical ventilation duration (MD -3.93; 95% CrI -7.98 to -0.02), prebiotics were most effective for preventing diarrhea (OR 0.24; 95% CrI 0.05-0.94) and TPN was the least effective in shortening hospital length of stay (MD 4.23; 95% CrI 0.97-7.33). Conclusions: Amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. Take-Home Message: Nosocomial infection is a leading cause of mortality in critically ill patients in the ICU. However, the efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition and total parenteral nutrition in preventing nosocomial infection in critically ill adults has been questioned. The network meta-analysis provides evidence that amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. The results of this study will provide a new scientific basis and a new idea for the debate on the efficacy of synbiotics and other treatments in the improvement of prognosis in critically ill adult patients. Tweet: Synbiotic prevents nosocomial infection in critically ill adults, while total parenteral nutrition has the adverse curative.

Nucleotide polymorphism in ARDS outcome: a whole exome sequencing association study.

BACKGROUND: Genetic locus were identified associated with acute respiratory distress syndrome (ARDS). Our goal was to explore the associations between genetic variants and ARDS outcome, as well as subphenotypes. METHODS: This was a single-center, prospective observational trial enrolling adult ARDS patients. After baseline data were collected, blood samples were drawn to perform whole exome sequencing, single nucleotide polymorphism (SNP)/insertion-deletion to explore the quantitative and functional associations between genetic variants and ICU outcome, clinical subphenotypes. Then the lung injury burden (LIB), which was defined as the ratio of nonsynonymous SNP number per megabase of DNA, was used to evaluate its value in predicting ARDS outcome. RESULTS: A total of 105 ARDS patients were enrolled in the study, including 70 survivors and 35 nonsurvivors. Based on the analysis of a total of 65,542 nonsynonymous SNP, LIB in survivors was significantly higher than nonsurvivors [1,892 (1,848-1,942)/MB versus 1,864 (1,829-1,910)/MB, P=0.018], while GO analysis showed that 60 functions were correlated with ARDS outcome, KEGG enrichment analysis showed that SNP/InDels were enriched in 13 pathways. Several new SNPs were found potentially associated with ARDS outcome. Analysis of LIB was used to determine its outcome predicting ability, the area under the ROC curve of which was only 0.6103, and increase to 0.712 when combined with APACHE II score. CONCLUSIONS: Genetic variants are associated with ARDS outcome and subphenotypes; however, their prognostic value still need to be verified by larger trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT02644798. Registered 20 April 2015.

Leukocyte kinetics during the early stage acts as a prognostic marker in patients with septic shock in intensive care unit.

ABSTRACT: The leukocytes play an important role in immune function during sepsis. We performed a retrospective study to investigate if leukocytes kinetics was associated with survival in critically ill patients with septic shock in intensive care unit (ICU).Patients with septic shock from January 1, 2014 to June 30, 2018 in our ICU were included. We extracted the demographic, clinical and laboratory data, comorbidities from our clinical database. The number of white blood cell, neutrophil and lymphocyte on day 1 and day 3 after diagnosis were collected and neutrophil to lymphocyte ratios (NLR) were calculated. Our primary outcome was 28-day mortality. Univariate and multivariate logistic regression models and cox proportional risk model were used to analyze the association between the leukocytes kinetics during first 3 days after ICU admission and the day-28 mortality.A total of 1245 septic shock patients with a 28-day mortality of 35.02% were included into analysis. There were no significant difference of lymphocyte number (0.83 ±â€Š0.02 vs 0.80 ±â€Š0.04, P = .552) between survival and non-survivals on day 1. However, the lymphocyte counts was significantly lower (0.95 ±â€Š0.03 vs 0.85 ±â€Š0.04, P = .024) on the third day. Both multivariate logistic and Cox regression analysis showed that lymphocyte counts on day 3 were associated with day-28 mortality. Moreover, Kaplan-Meier survival analysis revealed that increasing in lymphocyte counts and decreasing WBC, neutrophils and NLR during the first 3 days after diagnosis were associated with longer survival.Leukocytes kinetics during the first 3 days is a valuable prognostic marker in patients with septic shock in the ICU.