Impact of red blood cell transfusion and hemoglobin threshold on 1-year mortality among surgical sepsis survivors: A propensity score matching study.

BACKGROUND: Despite the fact that red blood cell (RBC) transfusion is commonly applied in surgical intensive care unit (ICU), the effect of RBC transfusion on long-term outcomes remains undetermined. We aimed to explore the association between RBC transfusion and the long-term prognosis of surgical sepsis survivors. METHODS: This retrospective study was conducted on adult sepsis patients admitted to a tertiary surgical ICU center in China. Patients were divided into transfusion and non-transfusion groups based on the presence of RBC transfusion. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)were performed to balance the potential confounders. RESULTS: A total of 1421 surgical sepsis survivors were enrolled, including 403 transfused patients and 1018 non-transfused patients. There was a significant difference in 1-year mortality between the two groups (23.1 â€‹% vs 12.7 â€‹%, HR: 1.539, 95 â€‹% confidence interval [CI]: 1.030-2.299, P â€‹< â€‹0.001). After PSM and IPTW, transfused patients still showed significantly increased 1-year mortality risks compared to non-transfused individuals (PSM: 23.6 â€‹% vs 15.9 â€‹%, HR 1.606, 95 â€‹% CI 1.036-2.488 â€‹P â€‹= â€‹0.034; IPTW: 20.1 â€‹% vs 12.9 â€‹%, HR 1.600, 95 â€‹% CI 1.040-2.462 â€‹P â€‹= â€‹0.032). Among patients with nadir hemoglobin below 70 â€‹g/L, 1-year mortality risks in both groups were similar (HR 1.461, 95 â€‹% CI 0.909-2.348, P â€‹= â€‹0.118). However, among patients with nadir hemoglobin above 70 â€‹g/L, RBC transfusion was correlated with increased 1-year mortality risk (HR 1.556, 95 â€‹% CI 1.020-2.374, P â€‹= â€‹0.040). CONCLUSION: For surgical sepsis survivors, RBC transfusion during ICU stay was associated with increased 1-year mortality, especially when patients show hemoglobin levels above 70 â€‹g/L.

Exploring the optimal range of central venous pressure in sepsis and septic shock patients: A retrospective study in 208 hospitals.

BACKGROUND: The aim of this study was to investigate the optimal CVP range in sepsis and septic shock patients admitted to intensive care unit. METHODS: We performed a retrospective study with adult sepsis patients with CVP records based on the eICU Collaborative Research Database. Multivariable logistic regression was performed to explore the associations between CVP level and hospital mortality. Non-linear correlations and optimal CVP range were explored using restricted cubic splines (RCS). RESULTS: A total of 5302 sepsis patients were included in this study. Patients in 4-8 mmHg group owned the lowest odds ratio for raw hospital mortality (19.7%). The logistic regression analyses revealed that hospital death risk increased significantly when mean CVP level exceeds 12 mmHg compared to 4-8 mmHg level. U-shaped association of CVP with hospital mortality was revealed by RCS model in septic shock patients and the optimal range was 5.6-12 mmHg. While, there was a J-shaped trend for non-septic shock patients. For non-septic shock patients, patients had an increased risk of hospital death only if CVP exceeded 11 mmHg. CONCLUSIONS: We observed U-shaped association between mean CVP level and hospital mortality in septic shock patients and J-shaped association in non-septic shock patients. This may imply that patients with different severity of sepsis have different CVP requirements. We need to monitor and manage CVP according to the circulatory status of the sepsis patient.

Improving Intestinal Barrier Function in Sepsis by Partially Hydrolysed Guar Gum via the Suppression of the NF-κB/MLCK Pathway.

Partially hydrolyzed guar gum (PHGG) protects against intestinal barrier dysfunction and can ameliorate some intestinal diseases. However, whether PHGG has a role in protecting intestinal barrier function (IBF) during sepsis remains unclear. This study aimed to investigate the role and probable mechanism of PHGG in the intestinal mucosa in sepsis. A rat sepsis model was constructed using cecal ligation and puncture (CLP). FITC-dextran 4 (FD-4) flux, serum inflammatory mediator levels, tight junction (TJ) levels, jejunum mucosa pathology, and epithelial intercellular junction ultrastructure were monitored to evaluate the effect of PHGG on IBF. Caco-2 monolayers were used to study the impact and mechanism of PHGG on lipopolysaccharide (LPS)-induced barrier dysfunction in vitro. The expression of zonula occludens protein-1 and occludin and the location of P65 were studied by immunofluorescence. Nuclear factor kappa B (NF-κB) and myosin light chain kinase 3 (MLCK) pathway-related protein expression was verified by quantitative reverse transcriptase polymerase chain reaction or western blotting. The results indicated that the jejunal mucosa structure was destroyed, the villi were disrupted and shortened, and neutrophil infiltration was evident in the septic rats. Compared to Sham group, spetic rats had increased Chiu's score, serum inflammatory mediator levels, and FD-4 flux but decreased TJ and gap junction density. In addition, the expression of MLCK, p-MLC, and TJ proteins and the expression of P65 in the nucleus were increased in septic rats. Furthermore, compared to those in the Control group, LPS-treated Caco-2 cells showed lower cell viability and transepithelial electrical resistance, while had higher FD-4 flux and the expression of MLCK, p-MLC, TJ proteins and P65 in the nucleus. PHGG pretreatment reversed the above effects induced by CLP or LPS treatment. Moreover, SN50, an NF-κB inhibitor, attenuated the above effects of LPS on Caco-2 cells. Overall, PHGG reduced inflammation, increased TJ protein expression and localization, and relieved damage to the TJ structure and intestinal permeability through suppression of the NF-κB/MLCK pathway. This study provides new insights into the role of PHGG in sepsis therapy.

Substantial decline of organ preservation fluid contamination following adoption of ischemia-free liver transplantation: a post-hoc analysis.

INTRODUCTION: Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. METHODS: A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. RESULTS: Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. CONCLUSION: PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.

Structured postoperative handover protocol improves efficiency and quality of interdisciplinary communication and nursing care in surgical intensive care unit: a randomized controlled trial.

This study aimed to evaluate the effectiveness of a structured postoperative handover protocol for postoperative transfer to the SICU. This study was a randomized controlled trial conducted in a comprehensive teaching hospital in China. Patients who were transferred to the SICU after surgery were randomly divided into two groups. The intervention group underwent postoperative structured handover protocol, and the control group still applied conventional oral handover. A total of 101 postoperative patients and 50 clinicians were enrolled. Although the intervention group did not shorten the handover duration (6.18 ± 1.66 vs 5.94 ± 1.91; P = 0.505), the handover integrity was significantly improved, mainly reflected in fewer information omissions (1.44 ± 0.97 vs 0.67 ± 0.62; P < 0.001), fewer additional questions raised by ICU physicians (1.06 ± 1.04 vs 0.24 ± 0.43; P < 0.001) and fewer additional handovers via phone call (16% vs 3.9%; P = 0.042). The total score of satisfaction of the intervention group was significantly higher than that of the control group (76.44 ± 7.32 vs 81.24 ± 6.95; P = 0.001). With respect to critical care, the incidence of stage I pressure sore within 24 h was lower in the intervention group than in the control group (20% vs 3.9%, P = 0.029). Structured postoperative handover protocol improves the efficiency and quality of interdisciplinary communication and clinical care in SICU.Trial registration This study was registered in China on January 8th, 2022 at Chinese Clinical Trial Registry (ChiCTR2200055400).

Comparing Two Methods of Reducing Hospital Toilet Aerosols.

BACKGROUND: When flushed, uncovered hospital toilets have been shown to generate aerosols potentially containing bacteria, viruses, and hazardous drugs, which can be inhaled by healthcare workers and contaminate surfaces. Guidelines recommend placing a plastic-backed absorbent pad (PBP) over the toilet, although no studies have evaluated the effectiveness of this intervention. OBJECTIVES: The purpose of this study was to evaluate the effectiveness of using a PBP versus the Splashblocker®, a solid, reusable engineering barrier control, to reduce post-flush aerosol particles. METHODS: Aerosol measurements were taken with an optical particle counter in a bathroom testing chamber equipped with a commercial hospital toilet and flushometer valve. Three tests were performed at a height of 16 inches above the floor and 40 inches above the floor. FINDINGS: Both the PBP and the Splashblocker significantly reduced the number of post-flush particles by more than 99% at 16 inches above the floor and 40 inches above the floor. The results indicate that both interventions are equally beneficial in reducing aerosols after flushing a hospital toilet.

Pharmacokinetics of Voriconazole in Peritoneal Fluid of Critically Ill Patients.

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Developing an Interpretable Machine Learning Model to Predict in-Hospital Mortality in Sepsis Patients: A Retrospective Temporal Validation Study.

BACKGROUND: Risk stratification plays an essential role in the decision making for sepsis management, as existing approaches can hardly satisfy the need to assess this heterogeneous population. We aimed to develop and validate a machine learning model to predict in-hospital mortality in critically ill patients with sepsis. METHODS: Adult patients fulfilling the definition of Sepsis-3 were included at a large tertiary medical center. Relevant clinical features were extracted within the first 24 h in ICU, re-classified into different genres, and utilized for model development under three strategies: "Basic + Lab", "Basic + Intervention", and "Whole" feature sets. Extreme gradient boosting (XGBoost) was compared with logistic regression (LR) and established severity scores. Temporal validation was conducted using admissions from 2017 to 2019. RESULTS: The final cohort included 24,272 patients, of which 4013 patients formed the test cohort for temporal validation. The trained and fine-tuned XGBoost model with the whole feature set showed the best discriminatory ability in the test cohort with AUROC as 0.85, significantly higher than the XGBoost "Basic + Lab" model (0.83), the LR "Whole" model (0.82), SOFA (0.63), SAPS-II (0.73), and LODS score (0.74). The performance in varying subgroups remained robust, and predictors, such as increased urine output and supplemental oxygen therapy, were crucially correlated with improved survival when interpretability was explored. CONCLUSIONS: We developed and validated a novel XGBoost-based model and demonstrated significantly improved performance to LR and other scores in predicting the mortality risks of sepsis patients in the hospital using features in the first 24 h.

Population pharmacokinetics and limited sampling strategies of polymyxin B in critically ill patients.

OBJECTIVES: To characterize the pharmacokinetics (PK) of polymyxin B in Chinese critically ill patients. The factors significantly affecting PK parameters are identified, and a limited sampling strategy for therapeutic drug monitoring of polymyxin B is explored. METHODS: Thirty patients (212 samples) were included in a population PK analysis. A limited sampling strategy was developed using Bayesian estimation, multiple linear regression and modified integral equations. Non-linear mixed-effects models were developed using Phoenix NLME software. RESULTS: A two-compartment population PK model was used to describe polymyxin B PK. Population estimates of the volumes of central compartment distribution (V) and peripheral compartment distribution (V2), central compartment clearance (CL) and intercompartmental clearance (Q) were 7.857 L, 12.668 L, 1.672 L/h and 7.009 L/h. Continuous renal replacement therapy (CRRT) significantly affected CL, and body weight significantly affected CL and Q. The AUC0-12h of polymyxin B in patients with CRRT was significantly lower than in patients without CRRT. CL and Q increased with increasing body weight. A limited sampling strategy was suggested using a two-sample scheme with plasma at 0.5h and 8h after the end of infusion (C0.5 and C8) for therapeutic drug monitoring in the clinic. CONCLUSIONS: A dosing regimen should be based on body weight and the application of CRRT. A two-sample strategy for therapeutic drug monitoring could facilitate individualized treatment with polymyxin B in critically ill patients.

The neutrophil-to-lymphocyte ratio: A potential predictor of poor prognosis in adult patients with trauma and traumatic brain injury.

Purpose: This study aimed to determine the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in critically ill trauma patients. Methods: This retrospective study involved adult trauma patients from 335 intensive care units (ICUs) at 208 hospitals stored in the eICU database. The primary outcome was ICU mortality. The lengths of ICU and hospital stay were calculated as the secondary outcomes. The multivariable logistic regression model was used to identify independent predictors of mortality. To identify the effect of the NLR on survival, a 15-day survival curve was used. Results: A total of 3,865 eligible subjects were enrolled in the study. Univariate analysis showed that patients in the group with a higher NLR were more likely to receive aggressive methods of care delivery: mechanical ventilation, vasopressor, and antibiotics ( P < 0.001 for all). The ICU, in-hospital, and 15-day mortality rates of the four groups increased in turn (P < 0.001 for all). The multivariable logistic Cox regression model indicated that a higher NLR was an independent risk factor of ICU mortality in trauma patients. ROC analysis showed that the NLR had better predictive capacity on the mortality of patients with traumatic brain injury (TBI) than those with trauma (AUC 0.725 vs. 0.681). An NLR > 7.44 was an independent risk factor for ICU death in patients with TBI (OR: 1.837, 95% CI: 1.045-3.229) and TBI victims whose NLR > 7.44 had a 15-day survival disadvantage (P = 0.005). Conclusion: A high NLR is associated with a poor prognosis in trauma patients, even worse in patients with TBI. An NLR > 7.44 is an independent risk factor for death in patients with TBI.

Validation of a High Flow Rate Puff Topography System Designed for Measurement of Sub-Ohm, Third Generation Electronic Nicotine Delivery Systems.

There are few known puff topography devices designed solely for gathering electronic cigarette puff topography information, and none made for high-powered sub-ohm devices. Ten replicate Bernoulli flow cells were designed and 3D printed. The relationship between square root of pressure difference and flow rate was determined across 0−70 L/min. One representative flow cell was used to estimate puff volume and flow rate under six simulated puffing regimes (0.710 L, 2.000 L and 3.000 L, at low and high flow rates) to determine the system's accuracy and utility of using dual pressure sensors for flow measurement. The relationship between flow rate and square root of pressure differential for the ten replicate cells was best fit with a quadratic model (R2 = 0.9991, p < 0.0001). The higher-pressure sensor was accurate at both low and high flow rates for 0.71 L (102% and 111% respectively), 2.00 L (96% and 103% respectively), and 3.00 L (100.1% and 107% respectively) but the lower-pressure sensor provided no utility, underpredicting volume and flow. This puff topography system generates very little resistance to flow, easily fits between user's atomizer and mouthpiece, and is calibrated to measure flows up to 70 L/min.

Reducing the particles generated by flushing institutional toilets.

Airborne particles play a significant role in the transmission of SARS-CoV-2, the virus that causes COVID-19. A previous study reported that institutional flush-O-meter (FOM) toilets can generate 3-12 times as many droplets as other toilets by splashing (large droplets) and bubble bursting (fine droplets). In this study, an aerosol suppression lid was evaluated to measure the reduction of particles by size using three metrics; number, surface area, and mass concentrations. To quantify toilet flush aerosol over time, detailed particle size distributions (from 0.016-19.81 µm across 152 size bins) were measured from a FOM toilet in a controlled-environment test chamber, without ventilation, with and without use of the suppression lid. Prior to each flushing trial, the toilet bowl water was seeded with 480 mL fluorescein at 10 mg/mL. A high-speed camera was used to record the large droplet movements after flushing. An ultraviolet-visible spectrophotometer was used to analyze the wipe samples to evaluate the contamination on the lid. The particle number, surface area, and mass concentrations without a lid were elevated compared to a lid in the first 90 sec. Overall, the lid reduced 48% of total number concentration, 76% of total surface area concentration, and 66% of total mass concentration, respectively. Depending on the particle size, the number concentration reduction percentage ranged from 48-100% for particles larger than 0.1 µm. Large droplets created by splashing were captured by the high-speed camera. Similar studies can be used for future particle aerodynamic studies. The fluorescein droplets deposited on the lid back sections, which were closer to the FOM accounted for 82% of the total fluorescein. Based on two-way ANOVA analysis, there were significant differences among both the experimental flushes (p = 0.0185) and the sections on the lid (p = 0.0146). Future work should explore the aerosolization produced by flushing and the performance of the lid in real restroom environments, where feces and urine exist in the bowl water and the indoor ventilation system is in operation.

Characteristics of Particles and Debris Released after Implantoplasty: A Comparative Study.

Titanium particles embedded on peri-implant tissues are associated with a variety of detrimental effects. Given that the characteristics of these detached fragments (size, concentration, etc.) dictate the potential cytotoxicity and biological repercussions exerted, it is of paramount importance to investigate the properties of these debris. This study compares the characteristics of particles released among different implant systems (Group A: Straumann, Group B: BioHorizons and Group C: Zimmer) during implantoplasty. A novel experimental system was utilized for measuring and collecting particles generated from implantoplasty. A scanning mobility particle sizer, aerodynamic particle sizer, nano micro-orifice uniform deposit impactor, and scanning electron microscope were used to collect and analyze the particles by size. The chemical composition of the particles was analyzed by highly sensitive microanalysis, microstructures by scanning electron microscope and the mechanical properties by nanoindentation equipment. Particles released by implantoplasty showed bimodal size distributions, with the majority of particles in the ultrafine size range (<100 nm) for all groups. Statistical analysis indicated a significant difference among all implant systems in terms of the particle number size distribution (p < 0.0001), with the highest concentration in Group B and lowest in Group C, in both fine and ultrafine modes. Significant differences among all groups (p < 0.0001) were also observed for the other two metrics, with the highest concentration of particle mass and surface area in Group B and lowest in Group C, in both fine and ultrafine modes. For coarse particles (>1 µm), no significant difference was detected among groups in terms of particle number or mass, but a significantly smaller surface area was found in Group A as compared to Group B (p = 0.02) and Group C (p = 0.005). The 1 first minute of procedures had a higher number concentration compared to the second and third minutes. SEM-EDS analysis showed different morphologies for various implant systems. These results can be explained by the differences in the chemical composition and microstructures of the different dental implants. Group B is softer than Groups A and C due to the laser treatment in the neck producing an increase of the grain size. The hardest implants were those of Group C due to the cold-strained titanium alloy, and consequently they displayed lower release than Groups A and B. Implantoplasty was associated with debris particle release, with the majority of particles at nanometric dimensions. BioHorizons implants released more particles compared to Straumann and Zimmer. Due to the widespread use of implantoplasty, it is of key importance to understand the characteristics of the generated debris. This is the first study to detect, quantify and analyze the debris/particles released from dental implants during implantoplasty including the full range of particle sizes, including both micro- and nano-scales.

Population pharmacokinetic model-guided optimization of intravenous voriconazole dosing regimens in critically ill patients with liver dysfunction.

STUDY OBJECTIVES: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN: Prospective pharmacokinetics study. SETTING: The intensive care unit in a tertiary-care medical center. PATIENTS: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS: Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS: A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.

Voriconazole pharmacokinetics in a critically ill patient during extracorporeal membrane oxygenation.

The pharmacokinetics (PK) of several drugs including antimicrobials might be highly altered during extracorporeal membrane oxygenation (ECMO) therapy. We present the change of voriconazole (VRC) PK during ECMO in a critically ill patient who received intravenous VRC at a maintenance dose of 200 mg every 12 h for empirical antifungal therapy. Two PK profiles were drawn before and after the initiation of ECMO therapy. Though the trough levels (both C0 and C12) with ECMO were slightly lower than that without ECMO (12.58 and 12.84 vs. 14.02 µg/mL), the peak levels and the area under the concentration-time curve from 0 h to 6 h (AUC0-6) were comparable (16.36 vs. 16.06 µg/mL and 90.78 vs. 91.45 µg·h/mL, respectively), indicating that VRC plasma exposure during ECMO therapy did not greatly decrease in our patient. The circuit factors including the type of membrane should be taken into account to further identify the effects of ECMO on the PK of VRC.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Size-resolved spatial distribution analysis of aerosols with or without the utilization of a novel aerosol containment device in dental settings.

The coronavirus disease 2019 pandemic has imposed unprecedented occupational challenges for healthcare professionals. In dentistry, handheld instruments such as air and electric handpieces, ultrasonic scalers, and air/water syringes are capable of generating aerosols, droplets, and splatter, thereby exposing dental professionals to airborne contaminants such as viruses, bacteria, and fungi. The objective of the present study was to determine the spatial distribution of aerosols by size (0.30 to 20.00 µm) and the efficacy of a novel aerosol containment device (ACD) in a large operatory room with 12 dental chairs. Real-time portable laser aerosol spectrometers were used to measure the size-resolved number concentration of aerosols generated by a collision nebulizer. Results reported demonstrate that aerosol number concentrations significantly decreased as a function of distance with or without the utilization of the ACD. The ACD was able to efficiently decrease (up to 8.56-fold) the number and size distribution of particles in a large dental clinic. The novel device demonstrated higher efficiency for particles shown to contain the highest levels of severe acute respiratory syndrome coronavirus 2 in Chinese hospitals, thereby showing great promise to potentially decrease the spreading of nosocomial pathogens in dental settings.

Circulating microRNAs as novel diagnostic biomarkers and prognostic predictors for septic patients.

This study was to find out novel miRNAs whether could be used as diagnostic or prognostic biomarkers in sepsis. We used miRNAs microarray assays and further confirmed the levels of miRNAs in 151 septic patients' plasma. 56 miRNAs were up-regulated and 74 miRNAs down-regulated in septic patients compared with the healthy volunteers. But only miR-519c-5p and miR-3622b-3p were up-regulated in both septic and septic shock patients. The levels of miR-519c-5p and miR-3622b-3p were statistically higher in 151 septic patients than healthy controls on day 1. The AUC for miR-519c-5p was 0.79 (95% CI, 0.688-0.892, p = 0.001) in the diagnosis of sepsis, and the AUC for miR-3622b-3p 0.752 (95% CI, 0.622-0.881, p = 0.003). The AUC for the combination of these two miRNAs was 0.831 (95% CI, 0.74-0.923, p < 0.001). Besides, the AUC for miR-519c-5p was 0.597 (p = 0.043) in predicting 28-day mortality. MiR-519c-5p, miR-3622b-3p were novel biomarkers for diagnosing septic patients. High miR-519c-5p levels suggest a worse short-term prognosis. CLINICAL TRIAL REGISTRATION INFORMATION: Name of the registry: Diagnostic and prognostic value of circulating miRNA in patients with sepsis; Trial registration ID: ChiCTR-DDD-17013150; registered 30 October 2017; http://www.chictr.org.cn/edit.aspx?pid=22528&htm=4.

Utilization of Antibacterial Nanoparticles in Photocurable Additive Manufacturing of Advanced Composites for Improved Public Health.

This paper presents the additive manufacturing and characterization of nanoparticle-reinforced photocurable resin-based nanocomposites with a potential antimicrobial function for improved public health applications. Two types of photocurable resins are reinforced by titanium dioxide (TiO2) or zinc oxide (ZnO) nanoparticles with average diameters in the 10-30 nm range to provide antimicrobial properties. The developed nanocomposites can be additively manufactured using the digital light processing method with an outstanding surface quality and precise geometrical accuracy. Experimental characterizations are conducted to investigate key mechanical properties of the 3D printed nanocomposites, including Young's Modulus, tensile strength, and abrasion resistance. Specimens produced were observed to demonstrate the following characteristics during testing. Tensile strength increased by 42.2% at a maximum value of 29.53 MPa. The modulus of elasticity increased by 14.3%, and abrasion resistance increased by 15.8%. The proper dispersion of the nanoparticles within the cured resin is validated by scanning electron images. The wettability and water absorption testing results indicate that the developed nanocomposites have an outstanding water resistance capability. The pairing of digital light processing with these novel nanocomposites allows for the creation of complex composite geometries that are not capable through other manufacturing processes. Therefore, they have the potential for long-term usage to improve general public health with antimicrobial functionality. The pairing of an unmodified photocurable resin with a 1% ZnO concentration demonstrated the most promise for commercial applications.