Association between the ß-blocker use and patients with sepsis: a cohort study.

Objective: This study aimed to assess whether ß-blockers are associated with mortality in patients with sepsis. Method: We conducted a retrospective cohort study of patients with sepsis using the Medical Information Market for Intensive Care (MIMIC)-IV and the emergency intensive care unit (eICU) databases. The primary outcome was the in-hospital mortality rate. The propensity score matching (PSM) method was adopted to reduce confounder bias. Subgroup and sensitivity analyses were performed to test the stability of the conclusions. Results: We included a total of 61,751 patients with sepsis, with an overall in-hospital mortality rate of 15.3% in MIMIC-IV and 13.6% in eICU. The inverse probability-weighting model showed that in-hospital mortality was significantly lower in the ß-blockers group than in the non-ß-blockers group [HR = 0.71, 95% CI: 0.66-0.75, p < 0.001 in MIMIC-IV, and HR = 0.48, 95% CI: 0.45-0.52, p < 0.001 in eICU]. In subgroups grouped according to sex, age, heart rate, APSIII, septic shock, and admission years, the results did not change. Conclusion: ß-blocker use is associated with lower in-hospital mortality in patients with sepsis, further randomized trials are required to confirm this association.

Association Between Wait Time of Central Venous Pressure Measurement and Outcomes in Critical Patients With Acute Kidney Injury: A Retrospective Cohort Study.

Background: Hemodynamic management is of paramount importance in patients with acute kidney injury (AKI). Central venous pressure (CVP) has been used to assess volume status. We intended to identify the optimal time window in which to obtain CVP to avoid the incidence of adverse outcomes in patients with AKI. Methods: The study was based on the Medical Information Mart for Intensive Care (MIMIC) IV database. The primary outcome was in-hospital mortality. Secondary outcomes included the number of ICU-free days and norepinephrine-free days at 28 days after ICU admission, and total fluid input and fluid balance during the first and second day. A time-dose-response relationship between wait time of CVP measurement and in-hospital mortality was implemented to find an inflection point for grouping, followed by propensity-score matching (PSM), which was used to compare the outcomes between the two groups. Results: Twenty Nine Thousand and Three Hundred Thirty Six patients with AKI were enrolled, and the risk of in-hospital mortality increased when the CVP acquisition time was >9 h in the Cox proportional hazards regression model. Compared with 8,071 patients (27.5%) who underwent CVP measurement within 9 h and were assigned to the early group, 21,265 patients (72.5%) who delayed or did not monitor CVP had a significantly higher in-hospital mortality in univariate and multivariate Cox regression analyses. After adjusting for potential confounders by PSM and adjusting for propensity score, pairwise algorithmic, overlap weight, and doubly robust analysis, the results were still stable. The HRs were 0.58-0.72, all p < 0.001. E-value analysis suggested robustness to unmeasured confounding. Conclusions: Among adults with AKI in ICU, increased CVP wait time was associated with a greater risk of in-hospital mortality. In addition, early CVP monitoring perhaps contributed to shortening the length of ICU stays and days of norepinephrine use, as well as better fluid management.

Association between Wait Time for Transthoracic Echocardiography and 28-Day Mortality in Patients with Septic Shock: A Cohort Study.

Background: the optimal timing of Transthoracic echocardiography (TTE) performance for patients with septic shock remains unexplored. Methods: a retrospective cohort study included patients with septic shock in the MIMIC-Ⅲ database. Risk-adjusted restricted cubic splines modeled the 28-day mortality according to time elapsed from ICU admission to receive TTE. The cut point when a smooth curve inflected was selected to define early and delayed group. We applied propensity score matching (PSM) to ensure our findings were reliable. Causal mediation analysis was used to assess the intermediate effect of fluid balance within 72 h after ICU admission. Results: 3264 participants were enrolled and the risk of 28-day mortality increased until the wait time was around 10 h (Early group) and then was relatively flat afterwards (Delayed group). A beneficial effect of early TTE in terms of the 28-day mortality was observed (HRs 0.73−0.78, all p < 0.05) in the PSM. The indirect effect brought by the fluid balance on day 2 and 3 was significant (both p = 0.006). Conclusion: early TTE performance might be associated with lower risk-adjusted 28-day mortality in patients with septic shock. Better fluid balance may have mediated this effect. A wait time within 10 h after ICU may represent a threshold defining progressively increasing risk.

[Relationship of in-hospital mortality and using intra-aortic balloon pump with extracorporeal cardiopulmonary resuscitation in patients with cardiac arrest: a secondary analysis based on literature data].

OBJECTIVE: To assess the effect of intra-aortic balloon pump (IABP) on in-hospital mortality in patients with cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: A retrospective study was performed on 696 patients with intra-hospital cardiac arrest undergoing ECPR from Samsung Medical Center in Korea between January 2004 and December 2013. According to whether IABP was used, the patients were divided into ECPR group and ECPR+IABP group. Cox regression and propensity score matching (PSM) were used to examine the correlation between IABP usage and in-hospital mortality, and standardized mean difference (SMD) was used to check the degree of PSM. Survival analysis of in-hospital mortality was performed by the Kaplan-Meier method, and further analyzed by the Log-Rank test. Using the propensity score as weights, multiple regression model and inverse probability weighting (IPW) model were used for sensitivity analysis. In-hospital mortality, extracorporeal membrane oxygenation (ECMO) withdrawal success rate and neurological function prognosis were compared between the two groups. RESULTS: A total of 199 patients with cardiac arrest undergoing ECPR were included, including 120 males and 79 females, and the average age was (60.0±16.8) years. Thirty-one patients (15.6%) were treated with ECPR and IABP, and 168 patients (84.4%) only received ECPR. The total hospitalized mortality was 68.8% (137/199). The 1 : 1 nearest neighbor matching algorithm was performed with the 0.2 caliper value. The following variables were selected to generate propensity scores, including age, gender, race, marital status, insurance, admission type, service unit, heart rate, mean arterial pressure, respiratory rate, pulse oxygen saturation, white blood cell count. After the propensity score matching, 24 pairs of patients were successfully matched, with the average age of (63.0±12.8) years, including 31 males and 17 females. The in-hospital mortality was 72.6% (122/168) and 48.4% (15/31) in the ECPR group and the ECPR+IABP group [hazard ratio (HR) = 0.48, 95% confidence interval (95%CI) was 0.28-0.82, P = 0.007]. Multiple regression model, adjusted propensity score, PSM and IPW model showed that the in-hospital mortality in the ECPR+IABP group was significantly lower compared with the ECPR group (HR = 0.44, 0.50, 0.16 and 0.49, respectively, 95%CI were 0.24-0.79, 0.28-0.91, 0.06-0.39 and 0.31-0.77, all P < 0.05). The combined application of IABP could improve the ECMO withdrawal success rate [odds ratio (OR) = 8.95, 95%CI was 2.72-29.38, P < 0.001] and neurological prognosis (OR = 4.06, 95%CI was 1.33-12.40, P = 0.014) in adult cardiac arrest patients. CONCLUSIONS: In patients with cardiac arrest using ECPR, the combination of IABP was independently associated with lower in-hospital mortality, higher ECMO withdrawal success rate and better neurological prognosis.

Relationship between Driving Pressure and Mortality in Ventilated Patients with Heart Failure: A Cohort Study.

Background: Heart failure (HF) is a leading cause of mortality and morbidity worldwide, with an increasing incidence. Invasive ventilation is considered to be essential for patients with HF. Previous studies have shown that driving pressure is associated with mortality in acute respiratory distress syndrome (ARDS). However, the relationship between driving pressure and mortality has not yet been examined in ventilated patients with HF. We assessed the association of driving pressure and mortality in patients with HF. Methods: We conducted a retrospective cohort study of invasive ventilated adult patients with HF from the Medical Information Mart for Intensive Care-III database. We used multivariable logistic regression models, a generalized additive model, and a two-piecewise linear regression model to show the effect of the average driving pressure within 24 h of intensive care unit admission on in-hospital mortality. Results: Six hundred and thirty-two invasive ventilated patients with HF were enrolled. Driving pressure was independently associated with in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.18; P < 0.001) after adjusted potential confounders. A nonlinear relationship was found between driving pressure and in-hospital mortality, which had a threshold around 14.27 cmH2O. The effect sizes and CIs below and above the threshold were 0.89 (0.75 to 1.05) and 1.17 (1.07 to 1.30), respectively. Conclusions: There was a nonlinear relationship between driving pressure and mortality in patients with HF who were ventilated for more than 48 h, and this relationship was associated with increased in-hospital mortality when the driving pressure was more than 14.27 cmH2O.

Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study.

Background: Sepsis is a deadly disease worldwide. Effective treatment strategy of sepsis remains limited. There still was a controversial about association between preadmission metformin use and mortality in sepsis patients with diabetes. We aimed to assess sepsis-related mortality in patients with type 2 diabetes (T2DM) who were preadmission metformin and non-metformin users. Methods: The patients with sepsis and T2DM were included from Medical Information Mart for Intensive Care -III database. Outcome was 30-day mortality. We used multivariable Cox regression analyses to calculate adjusted hazard ratio (HR) with 95% CI. Results: We included 2,383 sepsis patients with T2DM (476 and 1,907 patients were preadmission metformin and non-metformin uses) between 2001 and 2012. The overall 30-day mortality was 20.1% (480/2,383); it was 21.9% (418/1,907), and 13.0% (62/476) for non-metformin and metformin users, respectively. After adjusted for potential confounders, we found that preadmission metformin use was associated with 39% lower of 30-day mortality (HR = 0.61, 95% CI: 0.46-0.81, p = 0.007). In sensitivity analyses, subgroups analyses, and propensity score matching, the results remain stable. Conclusions: Preadmission metformin use may be associated with reduced risk-adjusted mortality in patients with sepsis and T2DM. It is worthy to further investigate this association.

Association between metformin use on admission and outcomes in intensive care unit patients with acute kidney injury and type 2 diabetes: A retrospective cohort study.

PURPOSE: Acute kidney injury (AKI) occurs in more than half of intensive care unit patients. Effective prevention and treatment strategies for AKI remain limited. We aimed to assess AKI-related mortality in patients with diabetes who were metformin and non-metformin users. MATERIALS AND METHODS: We included patients with AKI and type 2 diabetes (T2DM) from the Medical Information Mart for Intensive Care database. The 30-day mortality, neutrophil-to-lymphocyte ratio, and length of hospital stay were compared between patients with and without metformin prescriptions. We used multivariable Cox proportional hazards regression, propensity score analysis, and an inverse probability-weighting model to ensure the robustness of our findings. RESULTS: We included 4328 patients with AKI and T2DM (998 and 3330 patients were metformin and non-metformin users, respectively). The overall 30-day mortality was 14.2% (613/4328); it was 15.7% (523/3330) and 9.0% (90/998) for non-metformin and metformin users, respectively. In the inverse probability-weighting model, metformin use was associated with 37% lower 30-day mortality (HR = 0.63, 95% CI: 0.50-0.80, p < 0.0001). CONCLUSIONS: Metformin use may be associated with reduced risk-adjusted mortality in patients with AKI and T2DM. Further randomized controlled trials are needed to clarify this association.

Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos.

CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing.