Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial.

BACKGROUND: The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. METHODS: In China's Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration-time curve across 24 h at a steady state (ssAUC0-24) of 50-100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. RESULTS: This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan-Meier's 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0-24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. CONCLUSION: A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.

Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study.

BACKGROUND: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections. METHODS: The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. RESULTS: The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of Klebsiella pneumoniae. The mean duration of PMB therapy was 11 days (range 7-38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 109/l vs 9.28 × 109/l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%). CONCLUSIONS: Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.

Mapping knowledge structure and emerging trends of extracorporeal membrane oxygenation for acute respiratory distress syndrome: a bibliometric and visualized study.

Introduction: With the discovery of extracorporeal membrane oxygenation (ECMO), it is considered as a valuable tool for supporting the treatment of severe acute respiratory distress syndrome (ARDS). It has gained increasing attention, particularly during the COVID-19 epidemic. However, to date, no relevant bibliometric research on the association between ECMO and ARDS (ECMO-ARDS) has been reported. Our study aimed to summarize the knowledge structure and research focus of ECMO-ARDS through a bibliometric analysis. Method: Publications related to ECMO-ARDS from 2000 to 2022 were obtained from the Web of Science Core Collection (WoSCC). Research data underwent bibliometric and visual analysis by using CiteSpace, VOSviewer, and one online analysis platform. By analyzing the countries, institutions, journals, authors, the geographic distribution of research contributions as well as the leading institutions and researchers in this field were identified. Additionally, prominent journals and highly cited publications were highlighted, indicating their influence and significance in the field. Moreover, the co-citation references and co-occurring keywords provided valuable information on the major research topics, trends, and potential emerging frontiers. Results: A total of 1,565 publications from 60 countries/regions were retrieved. The annual publication number over time revealed exponential growth trends (R2 = 0.9511). The United States was dominant in ECMO-ARDS research, whereas the Univ Toronto was most productive institution. Prof Combes A published the most publications in this area. ASAIO Journal and Intensive Care Medicine were the most active and co-cited journals, respectively. Reference co-citation analysis showed that current research focus has shifted to COVID-related ARDS, multi-center studies, as well as prone positioning. Apart from the keywords "ECMO" and "ARDS", other keywords appearing at high frequency in the research field were "COVID-19", "mechanical ventilation", "extracorporeal life support", "respiratory failure", "veno-venous ECMO", "SARS-CoV-2", "outcome". Among them, keywords like "mortality", "veno-venous ECMO", "epidemiology", "obesity", "coagulopathy", "lung ultrasound", "inhalation injury", "noninvasive ventilation", "diagnosis", "heparin", "cytokine storm" has received growing interest in current research and also has the potential to continue to become research hotspots in the near future. Conclusion: This bibliometric analysis offers a comprehensive understanding of the current state of ECMO-ARDS research and can serve as a valuable resource for researchers, policymakers, and stakeholders in exploring future research directions and fostering collaborations in this critical field.

Artificial Intelligence in Intensive Care Medicine: Toward a ChatGPT/GPT-4 Way?

Although intensive care medicine (ICM) is a relatively young discipline, it has rapidly developed into a full-fledged and highly specialized specialty covering several fields of medicine. The COVID-19 pandemic led to a surge in intensive care unit demand and also bring unprecedented development opportunities for this area. Multiple new technologies such as artificial intelligence (AI) and machine learning (ML) were gradually being applied in this field. In this study, through an online survey, we have summarized the potential uses of ChatGPT/GPT-4 in ICM range from knowledge augmentation, device management, clinical decision-making support, early warning systems, and establishment of intensive care unit (ICU) database.

[Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate].

OBJECTIVE: To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate. METHODS: Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups. RESULTS: A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. (1) There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE II: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [µmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. (2) Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). (3) Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. (4) Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. CONCLUSIONS: CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway.

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.

Correction: Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway.

Correction for 'Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway' by Qian Bai et al., J. Mater. Chem. B, 2023, https://doi.org/10.1039/d3tb00929g.

Synthesis of ultra-fine conducting polyaniline micro/nanotubes using fiber template and their NH3 gas sensitivity.

We have recently fabricated ultra-fine conducting polyaniline (PANI) tubes with high gas sensitivity. This route includes two steps. Firstly, aniline polymerizes on the surface of a suitable fiber template prepared by electrospun nitrocellulose (NC). Then, the NC fiber template is dissolved and the ultra-fine PANI tubes are obtained. The structure of the conducting PANI tubes is characterized by IR spectrum and wide-angle X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results indicate that the PANI shows the shape of ultra-fine tubes with average inner diameter of 250-350 nm. The wall thickness of the ultra-fine PANI tubes increases with increasing the content of oxidant. The conductivity of the doped PANI tubes is about 6.9 x 10(-2) S. The results of gas sensitivity of the ultra-fine PANI tubes indicate that the PANI tubes can act as "electronic nose" to detect toxic NH3 gas below 20 ppm.