Carbon performance analysis of upgraded wastewater treatment plants in key control areas of the Ziya River Basin in China.

Wastewater treatment plants (WWTPs) are one of the largest sources of greenhouse gas (GHG) emissions, and they are also one of the largest energy consumption industries in urban systems. With the progression of upgrading and standard-rising, WWTPs both directly and indirectly increase carbon emissions from the increased investments in facilities and usages in electricity as well as chemical agents. Here, we collected operational data from 15 WWTPs in the key control areas of the Ziya River Basin in North China and accounted for the changes in carbon performance at different technical upgrade methods. Results showed that the average carbon emission performance increased by 0.487 kg CO2/m3 after the upgrade. Carbon emissions from electricity consumption, chemical usage, biochemical process and sludge treatment accounted for 42%, 17%, 24%, and 17% of the total improvement in carbon emission performance, respectively. Reducing energy consumption, regulating chemical use and sludge comprehensive utilization are the key to carbon emission reduction. It further proposes that the development of wastewater treatment discharge standards should fully consider the comprehensive utilization of water quality classification. Regions with favorable natural conditions should make full use of their advantages by adopting economically feasible, low-energy-consuming technologies such as constructed wetlands, which offer carbon sequestration and landscaping benefits. This study provides guidance on the selection of technological pathways for pollution reduction and carbon mitigation in the wastewater treatment industry and on achieving sustainable water resource utilization.

The Prognostic Significance of Lymph Node Ratio for Esophageal Cancer: A Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to investigate the prognostic significance of positive lymph node ratio (LNR) in patients with esophageal cancer. MATERIALS AND METHODS: The meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic search of relevant literature published until April 2022 in PubMed, EMBASE, and the Cochrane Library. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), with corresponding hazard ratios (HR) and 95% confidence intervals (CI). The included studies were subgrouped based on age, study area, adjuvant therapy, sensitivity analysis, and assessment of publication bias. We analyzed and discussed the results. RESULTS: We included 21 studies with 29 cohorts and 11,849 patients. The Newcastle-Ottawa Scale scores of the included studies were no less than six, indicating high research quality. The combined results of HR and 95% CI showed that patients with esophageal cancer with a lower LNR had better OS (HR, 2.58; 95% CI, 2.15-3.11; P < 0.001) and DFS (HR, 3.07; 95% CI, 1.85-5.10; P < 0.001). The subgroup analysis suggested that geographic region, age, and adjuvant therapy affected OS. When any cohort was excluded, no significant changes were observed in the pooled HR of the OS group, indicating reliable and robust results. Egger's and Begg's tests showed no potential publication bias in the studies that used OS as an outcome measurement index, indicating reliable results. Sensitivity analyses and assessments of publication bias (<10) were not performed because of an insufficient number of DFS studies. CONCLUSION: Patients with a lower positive LNR had a higher survival rate, suggesting that positive LNR may be a promising predictor of EC prognosis in esophageal cancer. After radical resection of esophageal cancer, the ratio of the number of dissected lymph nodes to the number of positive lymph nodes in patients with esophageal cancer should be considered to accurately evaluate the prognosis.

Lung morphology impacts the association between ventilatory variables and mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) patients with different lung morphology have distinct pulmonary mechanical dysfunction and outcomes. Whether lung morphology impacts the association between ventilatory variables and mortality remains unclear. Moreover, the impact of a novel combined ventilator variable [(4×DP) + RR] on morality in ARDS patients needs external validation. METHODS: We obtained data from the Chinese Database in Intensive Care (CDIC), which included adult ARDS patients who received invasive mechanical ventilation for at least 24 h. Patients were further classified into two groups based on lung morphology (focal and non-focal). Ventilatory variables were collected longitudinally within the first four days of ventilation. The primary outcome was 28-day mortality. Extended Cox regression models were employed to explore the interaction between lung morphology and longitudinal ventilatory variables on mortality. FINDINGS: We included 396 ARDS patients with different lung morphology (64.1% non-focal). The overall 28-day mortality was 34.4%. Patients with non-focal lung morphology have more severe and persistent pulmonary mechanical dysfunction and higher mortality than those with focal lung morphology. Time-varying driving pressure (DP) was more significantly associated with 28-day mortality in patients with non-focal lung morphology compared to focal lung morphology patients (P for interaction = 0.0039). The impact of DP on mortality was more significant than that of respiratory rate (RR) only in patients with non-focal lung morphology. The hazard ratio (HR) of mortality for [(4×DP) + RR] was significant in patients with non-focal lung morphology (HR 1.036, 95% CI 1.027-1.045), not in patients with focal lung morphology (HR 1.019, 95% CI 0.999-1.039). INTERPRETATION: The association between ventilator variables and mortality varied among patients with different lung morphology. [(4×DP) + RR] was only associated with mortality in patients with non-focal lung morphology. Further validation is needed.

Identification of indications for albumin administration in septic patients with liver cirrhosis.

BACKGROUND: Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the resuscitation stage of septic patients with liver cirrhosis, it remains unclear whether daily albumin administration can improve outcomes. Furthermore, the indications for initiating albumin therapy are not well defined. METHODS: Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 2.0) database. Marginal structural Cox models were employed to investigate the association between daily albumin infusion and 28-day mortality. We also aimed to explore under what circumstances enrolled patients could benefit most from albumin administration, based on the clinical parameters collected on the day of albumin infusion, including serum albumin concentration, serum lactate concentration, mean arterial pressure (MAP), and vasopressor dosage. RESULTS: A total of 2265 patients were included in the final analysis, of whom 1093 (48.3%) had received albumin treatment at least once. The overall 28-day mortality was 29.6%. After marginal structural modeling, daily albumin infusion was associated with a reduced risk of 28-day death (hazard ratio, 0.76; 95% CI 0.61-0.94). We found that patients benefit most from albumin infusion when initiated on the day of serum albumin concentration between 2.5 and 3.0 g/dL, serum lactate concentration greater than or equal to 2 mmol/L, MAP less than 60 mmHg, or vasopressor dosage between 0.2 and 0.3 mcg/kg/min (norepinephrine equivalent, NEE). CONCLUSIONS: Albumin infusion is associated with a reduction in mortality in septic patients with liver cirrhosis under specific circumstances. Serum albumin concentration, serum lactate, MAP, and vasopressor dosage were found to be modifiers of treatment effectiveness and should be considered when deciding to initial albumin infusion.

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).

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Vaccination for Negative Conversion Time of Nucleic Acid in Nonsevere COVID-19 Patients Infected by SARS-CoV-2 Omicron Variant.

SARS-CoV-2 Omicron variant is significantly different from all the previous variants and has rapidly replaced other variants as the dominant variant across the globe. An easily obtained, inexpensive, and rapid marker is needed to predict the negative conversion time (NCT) of nucleic acid in nonsevere COVID-19 patients infected by the Omicron variant. This retrospective study enrolled 226 patients infected by the Omicron variant between April 23, 2022, and May 16, 2022. The median age of the patients was 61 (interquartile range (IQR), 48-70) years, and 56.2% were male. 84 patients (37.2%) had at least one comorbidity, and 49 patients (21.7%) were classified into the moderate illness group. 145 patients (64.2%) received at least one dose of vaccine, in which 67 patients (29.6%) received a booster dose of vaccine. The median duration of NCT was 8 (IQR, 7-11) days. Univariate Cox analyses found that high NLR (>2.22), aged ≥65 years, vaccination, and moderate illness were significantly related to the NCT of nucleic acid. Multivariate Cox regression analysis showed that high NLR (NLR > 2.22, hazard ratio (HR):0.718, 95% CI: 0.534-0.964, p = 0.028) and vaccination (vaccinated ≥1 dose, HR: 1.536, 95% CI: 1.147-2.058, p = 0.004) were independently associated with NCT of nucleic acid. NLR is a rapid, simple, and useful prognostic factor for predicting NCT of nucleic acid in nonsevere COVID-19 patients with the Omicron variant. In addition, vaccination may also play a valuable role in predicting the NCT of nucleic acid.

Remifentanil versus Fentanyl for Analgesia in Mechanically Ventilated Patients: A Multicenter, Prospective, Randomized, Double-Blind, Parallel-Group Clinical Trial.

Purpose: Fentanyl is approved for use in many countries as an analgesic for patients requiring mechanical ventilation. However, it redistributes and accumulates easily in the plasma because of its long half-life. Remifentanil is a short context-sensitive half-life analgesic with a lower risk of redistribution and accumulation. Materials and methods: We conducted a multicenter, randomized, double-blind, non-inferiority trial. Critically ill patients requiring mechanical ventilation were randomly allocated to receive an infusion of either remifentanil or fentanyl for up to 72 h. The primary outcome was the analgesic success rate. A 95% confidence interval lower boundary greater than -8% for the difference between the groups was considered to indicate non-inferiority between the drugs. Results: A total of 137 patients received remifentanil (69) or fentanyl (68). Remifentanil's non-inferiority to fentanyl concerning its analgesic success rate was established (difference, 5.97%; 95% confidence interval: -3.99% to 16.35%). Mechanical ventilation duration, extubation duration, successful extubation, intensive care unit discharge, intensive care unit length of stay, and adverse events did not differ significantly between the two groups. Conclusions: Remifentanil was non-inferior to fentanyl regarding the analgesic success rate in critically ill patients requiring mechanical ventilation.

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial.

Recombinant human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody JS016 showed neutralizing and therapeutic effects in preclinical studies. The clinical efficacy and safety of the therapy needed to be evaluated. In this phase 2/3, multicenter, randomized, open-label, controlled trial, hospitalized patients with moderate or severe coronavirus disease 2019 (COVID-19) were randomly assigned in a 1:1 ratio to receive standard care or standard care plus a single intravenous infusion of JS016. The primary outcome was a six-level ordinal scale of clinical status on day 28 since randomization. Secondary outcomes include adverse events, 28-day mortality, ventilator-free days within 28 days, length of hospital stay, and negative conversion rate of SARS-CoV-2 nucleic acid on day 14. A total of 199 patients were randomized, and 197 (99 in the JS016 group and 98 in the control group) were analyzed. Most patients, 95 (96%) in the JS016 group and 97 (99%) in the control group were in the best category on day 28 since randomization. The odds ratio of being in a better clinical status was 0.31 (95% confidence interval [CI], 0.03 to 3.19; P = 0.33). Few adverse events occurred in both groups (3% in the JS016 group and 1% in the control group, respectively; P = 0.34). SARS-CoV-2 neutralizing antibody JS016 did not show clinical efficacy among hospitalized Chinese patients with moderate to severe COVID-19 disease. Further studies are needed to assess the efficacy of the neutralizing antibody to prevent disease deterioration and its benefits among groups of patients specified by disease course and severity. (This study has been registered at ClinicalTrials.gov under identifier NCT04931238.).

CD28 Agonism Improves Survival in Immunologically Experienced Septic Mice via IL-10 Released by Foxp3+ Regulatory T Cells.

Immune dysregulation during sepsis is mediated by an imbalance of T cell costimulatory and coinhibitory signaling. CD28 is downregulated during sepsis and is significantly altered on memory versus naive T cells. Thus, to study the role of CD28 during sepsis in a more physiologically relevant context, we developed a "memory mouse" model in which animals are subjected to pathogen infections to generate immunologic memory, followed by sepsis induction via cecal ligation and puncture. Using this system, we show that agonistic anti-CD28 treatment resulted in worsened survival in naive septic animals but conferred a significant survival advantage in immunologically experienced septic animals. Mechanistically, this differential response was driven by the ability of CD28 agonism to elicit IL-10 production from regulatory T cells uniquely in memory but not naive mice. Moreover, elevated IL-10 released by activated regulatory T cells in memory mice inhibited sepsis-induced T cell apoptosis via the antiapoptotic protein Bcl-xL. Together, these data demonstrate that immunologic experience is an important parameter that affects sepsis pathophysiology and can fundamentally change the outcome of modulating the CD28 pathway during sepsis. This study suggests that testing therapeutic strategies in immunologically experienced hosts may be one way to increase the physiologic relevance of rodent models in sepsis research.

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.

Prognostic Significance of Plasma Hepatocyte Growth Factor in Sepsis.

BACKGROUND: To assess any correlation of plasma hepatocyte growth factor (HGF) levels with relevant endothelial cell injury parameters and determine the prognostic value in septic patients. METHODS: A prospective, observational study was conducted in patients with sepsis admitted to the Department of Critical Care Medicine at the Zhongda Hospital from November 2017 to March 2018. Plasma HGF levels were measured by enzyme-linked immunosorbent assay in the first 24 h after admission (day 1) and on day 3. The primary endpoint was defined as all-cause 28-day mortality. Furthermore, we analyzed the correlation of HGF with relevant endothelial cell injury markers. RESULTS: Eighty-six patients admitted with sepsis were included. HGF levels of nonsurvivors were elevated compared to those of survivors on day 1 (1940.62 ± 74.66 pg/mL vs. 1635.61 ± 47.49 pg/mL; P = 0.002) and day 3 (1824.82 ± 137.52 pg/mL vs. 1309.77 ± 83.49 pg/mL; P = 0.001) and showed a strong correlation with von Willebrand factor (r = 0.45, P < 0.0001), lactate (r = 0.35, P = 0.0011), pulmonary vascular permeability index (r = 0.38, P = 0.0241), first 24 h fluid administration (r = 0.38, P < 0.0001), and sequential organ failure assessment score (r = 0.40, P = 0.0001). Plasma HGF levels were able to prognostically discriminate between survivors and nonsurvivors on day 1 (AUC: 0.72, 95%CI: 0.60-0.84) and day 3 (AUC: 0.77, 95%CI: 0.63-0.91). CONCLUSIONS: HGF levels are associated with sepsis and correlated with established markers of endothelial cell injury. Elevated HGF levels in sepsis patients are an efficient indicator of poor prognosis. TRIAL REGISTRATION: The study was registered in Clinical Trial (Registration Number: NCT02883231).

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.

Polarization-controllable perfect vortex beam by a dielectric metasurface.

A perfect vortex beam has been attracting tremendous attention due to the fact that its ring radius is independent of the topological charge. Taking advantage of the superposition principle of phase in Fourier space, we proposed to generate perfect vortex beam using propagation-phase-based dielectric metasurface, which exhibits production efficiency larger than 83.5%. Due to the sensitivity of propagation phase to the polarization of incident beam, two sets of phase profiles can be imposed on a single dielectric metasurface, enabling the simultaneous generation of dual perfect vortex beams. Based on this property, convenient control to the radius and/or topological charge of perfect vortex beam is achieved by switching the incident polarization between two orthogonal polarizations, without redesigning metasurface or changing optical path. What's more important, the crosstalk of these two channels is low, less than 4%. Thus, the propagation-phase method of producing perfect vortex beam will find significant applications in optical communication, particle trapping, particle manipulation and holographic display.

Neurally adjusted ventilatory assist as a weaning mode for adults with invasive mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Prolonged ventilatory support is associated with poor clinical outcomes. Partial support modes, especially pressure support ventilation, are frequently used in clinical practice but are associated with patient-ventilation asynchrony and deliver fixed levels of assist. Neurally adjusted ventilatory assist (NAVA), a mode of partial ventilatory assist that reduces patient-ventilator asynchrony, may be an alternative for weaning. However, the effects of NAVA on weaning outcomes in clinical practice are unclear. METHODS: We searched PubMed, Embase, Medline, and Cochrane Library from 2007 to December 2020. Randomized controlled trials and crossover trials that compared NAVA and other modes were identified in this study. The primary outcome was weaning success which was defined as the absence of ventilatory support for more than 48 h. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with accompanying 95% confidence interval (CI) were expressed. RESULTS: Seven studies (n = 693 patients) were included. Regarding the primary outcome, patients weaned with NAVA had a higher success rate compared with other partial support modes (OR = 1.93; 95% CI 1.12 to 3.32; P = 0.02). For the secondary outcomes, NAVA may reduce duration of mechanical ventilation (MD = - 2.63; 95% CI - 4.22 to - 1.03; P = 0.001) and hospital mortality (OR = 0.58; 95% CI 0.40 to 0.84; P = 0.004) and prolongs ventilator-free days (MD = 3.48; 95% CI 0.97 to 6.00; P = 0.007) when compared with other modes. CONCLUSIONS: Our study suggests that the NAVA mode may improve the rate of weaning success compared with other partial support modes for difficult to wean patients.

Clinical Characteristics and Outcomes of Patients With Severe COVID-19 Induced Acute Kidney Injury.

BACKGROUND: The incidence and outcome of Coronavirus disease 2019 (COVID-19)-induced kidney injury have been variably described. We aimed to describe the clinical characteristics, correlates and outcomes of critically ill patients with severe COVID-19 complicated by acute kidney injury (AKI). METHODS: We performed a multicenter retrospective cohort study of 671 critically ill adults with laboratory-confirmed COVID-19 from 19 hospitals in China between January 1 to February 29, 2020. Data were captured on demographics, comorbidities, symptoms, acute physiology, laboratory parameters, interventions, and outcomes. The primary exposure was ICU admission for confirmed COVID-19 related critically illness. The primary outcome was 28-day mortality. Secondary outcomes included factors associated with AKI, organ dysfunction, treatment intensity, and health services use. MEASUREMENTS AND MAIN RESULTS: Of 671 severe COVID-19 patients (median [IQR] 65 [56-73] years; male sex 65% (n = 434); hypertension 43% (n = 287) and APACHE II score 10 [7-14]), 39% developed AKI. Patients with AKI were older, had greater markers of inflammation and coagulation activation, and had greater acuity and organ dysfunction as presentation. Despite similar treatment with antivirals, patients with AKI had lower viral conversion negative rates than those without AKI. The 28-day mortality was much higher in AKI patients than patients without AKI (72% vs. 42%), and there was an increase in 28-day mortality according to the severity of AKI. Non-survivors were less likely to receive antiviral therapy [132 (70%) vs. 65 (88%)] compared with survivors and have lower viral negative conversion rate [17 (9%) vs. 47 (64%)]. CONCLUSIONS: Acute kidney injury was quite common in severe COVID-19 pneumonia, which associated with higher mortality.

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.

Association Between Pathophysiology and Volume of Distribution Among Patients With Sepsis or Septic Shock Treated With Imipenem: A Prospective Cohort Study.

BACKGROUND: This study was performed to explore the apparent volume of distribution (Vd) of imipenem in patients with sepsis or septic shock. METHODS: A prospective, observational, single-center study was conducted in patients with sepsis or septic shock. The patients were treated with 1 g of imipenem mixed with 200 mL of normal saline infused intravenously over a 3-hour period at 8-hour intervals. The concentration of imipenem was 5 mg/mL, and the rate of infusion was 5.5 mg/min. Blood samples for measuring imipenem serum concentrations with high-performance liquid chromatography were obtained before and at 0, 1, 2, 3, and 5 hours after drug infusion on study days 1 and 3. Pharmacokinetic parameters were calculated according to a noncompartment model. RESULTS: A total of 25 adult patients were enrolled in this study, of whom 15 were diagnosed with sepsis and 10 with septic shock. The initial Vd (Vc) of imipenem was significantly lower in the sepsis than that in the septic shock group (mean [standard deviation], 26.5 [7.1] vs 40.7 [11.0] L; P = .001). The Vc of imipenem was significantly related to serum albumin levels (r = -0.517; P = .008) as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (r = 0.606; P = .001). Multivariate linear regression identified serum albumin levels and APACHE II scores on day 1 as independent factors influencing the Vc of imipenem (P < .05). The difference in Vd between the imipenem steady state and the initial state was significantly higher in nonsurvivors than in survivors (mean [standard deviation], 1.7 [21.5] vs -13.1 [11.4] L; P = .046). CONCLUSIONS: APACHE II scores and serum albumin levels were found in this study to be independent factors that may affect the Vc of imipenem in patients with sepsis or septic shock. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov, NCT03308214.

Early- and Late-Onset Bloodstream Infections in the Intensive Care Unit: A Retrospective 5-Year Study of Patients at a University Hospital in China.

BACKGROUND: Limited data are available regarding the current microbiological characteristics of bloodstream infections (BSIs) in intensive care units (ICUs) in China. This retrospective study aimed to determine the epidemiology of early- and late-onset BSIs in our ICU. METHODS: We retrospectively collected data about ICU patients with BSI from 2013 to 2017. The patients were divided into the early- and late-onset BSI groups according to if BSI occurred within or beyond 48 hours after ICU admission. Univariate and multivariate logistic regression analyses were used to assess the risk factors for infection with multidrug resistant organisms (MDROs). RESULTS: Of 5474 ICU admissions, 486 (8.9%) patients with BSIs and with 500 microorganisms were included in this study, 246 (50.6%) of whom had early-onset BSIs. Two hundred and seventy patients were infected with MDROs. The proportion of MDRO infections was significantly higher among patients with late-onset BSIs than among those with early-onset BSIs (57.9% vs. 41.5%, P = .017). The ICU mortality rate was significantly higher in the late-onset BSI group (44.6% vs. 33.8%, P = .014) and early and appropriate antimicrobial treatment significantly improved the survival rate among patients with BSI (P < .001). CONCLUSIONS: MDROs affected more than half of patients with BSI in the ICU. Early appropriate empirical antimicrobial therapy could improve clinical outcome of patients with BSIs.

A Ventilator-associated Pneumonia Prediction Model in Patients With Acute Respiratory Distress Syndrome.

BACKGROUND: Mechanical ventilation is crucial for acute respiratory distress syndrome (ARDS) patients and diagnosis of ventilator-associated pneumonia (VAP) in ARDS patients is challenging. Hence, an effective model to predict VAP in ARDS is urgently needed. METHODS: We performed a secondary analysis of patient-level data from the Early versus Delayed Enteral Nutrition (EDEN) of ARDSNet randomized controlled trials. Multivariate binary logistic regression analysis established a predictive model, incorporating characteristics selected by systematic review and univariate analyses. The model's discrimination, calibration, and clinical usefulness were assessed using the C-index, calibration plot, and decision curve analysis (DCA). RESULTS: Of the 1000 unique patients enrolled in the EDEN trials, 70 (7%) had ARDS complicated with VAP. Mechanical ventilation duration and intensive care unit (ICU) stay were significantly longer in the VAP group than non-VAP group (P < .001 for both) but the 60-day mortality was comparable. Use of neuromuscular blocking agents, severe ARDS, admission for unscheduled surgery, and trauma as primary ARDS causes were independent risk factors for VAP. The area under the curve of the model was .744, and model fit was acceptable (Hosmer-Lemeshow P = .185). The calibration curve indicated that the model had proper discrimination and good calibration. DCA showed that the VAP prediction nomogram was clinically useful when an intervention was decided at a VAP probability threshold between 1% and 61%. CONCLUSIONS: The prediction nomogram for VAP development in ARDS patients can be applied after ICU admission, using available variables. Potential clinical benefits of using this model deserve further assessment.

The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey.

OBJECTIVES: We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. DESIGN: A cross-section survey study. SETTING: Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. PATIENTS: All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100 ICU admissions (95% CI, 15.8-25.4) with a 90-day mortality of 35.5%. The proportion of sepsis, severe sepsis, and septic shock were 3.10%, 43.6%, and 53.3% with a 90-day mortality of 2.78%, 17.69%, and 51.94%, respectively. Older age, low body weight, higher Sequential Organ Failure Assessment score, the number of systemic inflammatory response syndrome criteria, comorbid with heart failure, hematologic cancer, immunosuppression, higher level of lactate, infection site (pneumonia and bloodstream) were associated with 90-day mortality. CONCLUSIONS: Sepsis affects a fifth of patients admitted to ICUs in mainland China with a 90-day mortality rate of 35.5%. Our findings indicate that a large burden of sepsis, and we need to focus on sepsis as a quality improvement target in China given the high mortality. In addition, further studies are needed to delineate the epidemiology of sepsis outside the ICU.