[Is monitoring of anti-factor Xa levels required for low molecular weight heparin prophylaxis of venous thromboembolism in critically ill patients?]

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Xa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin III is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Xa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

[Related factors of viral nucleic acid change in critically ill patients with SARS-CoV-2 infection after treatment with Nirmatrelvir/Ritonavir: a single center retrospective cohort study].

OBJECTIVE: To describe negative conversion and rebound of patients with severe and critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after treatment with Nirmatrelvir/Ritonavir, and to analyze related factors associating with failure of SARS-CoV-2 negative conversion and relapse and prognosis. METHODS: A single center retrospective cohort study was conducted. Patients aged ≥ 16 years old who were diagnosed with severe or critical SARS-CoV-2 infection and took Nirmatrelvir/Ritonavir for 5 days in Peking University First Hospital from December 7, 2022 to January 27, 2023, were included. General characteristics and clinical data were collected from electronic medical record system. The Kaplan-Meier curve of SARS-CoV-2 negative conversion was drawn. Factors with P < 0.10 were incorporated into multivariate Logistic regression model to analyze the relationship between the factors and persistent nucleic acid positive and rebound. RESULTS: A total of 31 severe and 37 critical SARS-CoV-2 infection patients were included. The median duration from initiation of Nirmatrelvir/Ritonavir to negative conversion of SARS-CoV-2 for both was 6.0 days, and the negative conversion rate on day 15 was 93.5% and 86.5%, respectively. SARS-CoV-2 rebound was observed in 7 patients (11.3%), among whom were 1 severe patient and 6 critical patients. The above 7 patients with SARS-CoV-2 rebound and 6 patients with failure of SARS-CoV-2 negative conversion were compared with 55 patients with persistent negative conversion. Factors with P < 0.10, including the lowest lymphocyte count (LYM), the highest D-dimer, the highest procalcitonin (PCT), the lowest Ct value, cardiovascular diseases other than hypertension and coronary heart disease, were incorporated into multivariate Logistic regression analysis. The decreased LYM [odds ratio (OR) = 0.146, 95% confidence interval (95%CI) was 0.031-0.689, P = 0.015] and the increased PCT (OR = 2.008, 95%CI was 1.042-3.868, P = 0.037) were revealed to be independent risk factors of the failure of SARS-CoV-2 negative conversion or rebound. The proportion of mechanical ventilation and invasive ventilation were significantly higher in patients with persistent SARS-CoV-2 infection or rebound than those in patients with SARS-CoV-2 negative conversion (84.6% vs. 38.2%, 69.2% vs. 25.5%, both P < 0.01), but no significant difference in mechanical ventilation and invasive ventilation duration was observed. Compared with the patients with SARS-CoV-2 negative conversion, more patients with persistent SARS-CoV-2 infection or rebound were admitted to intensive care unit (ICU, 76.9% vs. 50.9%), and length of ICU stay in patients with persistent SARS-CoV-2 infection or rebound tended to be longer [days: 13.0 (10.3, 24.3) vs. 11.0 (5.3, 23.0), P > 0.05]. CONCLUSIONS: The decreased LYM and increased PCT are independent risk factors for the failure of SARS-CoV-2 negative conversion or rebound in patients with severe and critical SARS-CoV-2 infection. Attention should be paid to these patients for their poor prognosis.

Comparison of vonoprazan-based with rabeprazole-based dual therapy for treatment-naive patients of Helicobacter pylori infection: a prospective, multi-center, randomized controlled study.

BACKGROUND: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan-amoxicillin (VA) and 14-day rabeprazole-amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. METHODS: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. RESULTS: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). CONCLUSIONS: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication.

Diagnostic value of Kaiser score combined with breast vascular assessment from breast MRI for the characterization of breast lesions.

Objectives: The Kaiser scoring system for breast magnetic resonance imaging is a clinical decision-making tool for diagnosing breast lesions. However, the Kaiser score (KS) did not include the evaluation of breast vascularity. Therefore, this study aimed to use KS combined with breast vascular assessment, defined as KS*, and investigate the effectiveness of KS* in differentiating benign from malignant breast lesions. Methods: This retrospective study included 223 patients with suspicious breast lesions and pathologically verified results. The histopathological diagnostic criteria were according to the fifth edition of the WHO classification of breast tumors. The KS* was obtained after a joint evaluation combining the original KS and breast vasculature assessment. The receiver operating characteristic (ROC) curve was used for comparing differences in the diagnostic performance between KS* and KS, and the area under the receiver operating characteristic (AUC) was compared. Results: There were 119 (53.4%) benign and 104 (46.6%) malignant lesions in total. The overall sensitivity, specificity, and accuracy of increased ipsilateral breast vascularity were 69.2%, 76.5%, and 73.1%, respectively. The overall sensitivity, specificity, and accuracy of AVS were 82.7%, 76.5%, and 79.4%, respectively. For all lesions included the AUC of KS* was greater than that of KS (0.877 vs. 0.858, P = 0.016). The largest difference in AUC was observed in the non-mass subgroup (0.793 vs. 0.725, P = 0.029). Conclusion: Ipsilaterally increased breast vascularity and a positive AVS sign were significantly associated with malignancy. KS combined with breast vascular assessment can effectively improve the diagnostic ability of KS for breast lesions, especially for non-mass lesions.

Population pharmacokinetic analysis and dosing regimen optimization of teicoplanin in critically ill patients with sepsis.

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens. Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients' clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA. Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h-72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients. Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Differences in right hemisphere fNIRS activation associated with executive network during performance of the lateralized attention network tast by elite, expert and novice ice hockey athletes.

OBJECTIVE: We investigated brain activity associated with executive control attention network in elite, expert, and novice female ice hockey athletes during the revised lateralized attention network tast to determine whether the neural correlates of performance differ by skill level. METHODS: We collected and analyzed functional near-infrared spectroscopy data of 38 participants while performing the revised lateralized attention network tast. RESULTS: Elite players were significantly faster than novices (p = .005), and the experts' overall accuracy rate (ACC) was higher than that of novices (p = .001). The effect of the executive network on reaction time was higher in novices than in elite players (p = .008) and experts (p = .004). The effect of the executive network on the ACC was lower in elite players than in experts (p = .009) and novices (p = .010). Finally, elite player had higher flanker conflict effects on RT (p = .005) under the invalid cue condition. the effect of the alertness network and orientation on the ACC was lower in elite players than in novices (p = .000) and experts (p = .022). Changes in the blood oxygen level-dependent signal related to the flanker effect were significantly different in the right dorsolateral prefrontal cortex (F=3.980, p = .028) and right inferior frontal gyrus (F=3.703, p = .035) among the three groups. Elit players showed more efficient executive control (reduced conflict effect on ACC) (p = .006)in the RH.The changes related to the effect of blood oxygen level on orienting were significantly different in the right frontal eye fields (F=3.883, p = .030) among the three groups, Accompanied by significant activation of the right dorsolateral prefrontal cortex(p = .026). CONCLUSION: Our findings provide partial evidence of the superior cognitive performance and high neural efficiency of elite ice hockey players during cognitive tasks. These results demonstrate the right hemisphere superiority for executive control.We also found that specific brain activation in hockey players does not show a clear and linear relationship with skill level.

Preoperative dipstick albuminuria is associated with acute kidney injury in high-risk patients following non-cardiac surgery: a single-center prospective cohort study.

PURPOSE: This study aimed to investigate the association between preoperative dipstick albuminuria (DA) and acute kidney injury (AKI) in high-risk patients following non-cardiac surgery. METHODS: This was a single-center prospective cohort study. Adult patients with high risk of AKI undergoing non-cardiac surgery were enrolled. The primary outcome was AKI, defined according to KDIGO criteria within 7 days following non-cardiac surgery. DA status was determined by urinalysis performed within 24 h of hospital admission. Multivariate logistic regression model was used to analyze the association between preoperative DA and postoperative AKI. RESULTS: During the study period, 552 patients were enrolled and 8.5% of them developed postoperative AKI. The overall rate of preoperative positive DA was 26.4% with 30 and ≥ 100 mg/dL DA accounting for 19.2% and 7.2%, respectively. Patients with more severe preoperative DA had much higher rate of postoperative AKI (5.2% in patients with negative or trace DA, 13.2% in patients with 30 mg/dL DA and 30.0% in patients with ≥ 100 mg/dL DA, P < 0.001). After adjusting for several perioperative variables, preoperative 30 mg/dL DA (OR 2.575; 95% CI 1.049-6.322; P = 0.039) and ≥ 100 mg/dL DA (OR 3.868; 95% CI 1.246-12.010; P = 0.019) showed an independent association with postoperative AKI. In addition, patients with higher DA status demonstrated significantly increased level of postoperative urine biomarkers and their ratio to urine creatinine. CONCLUSIONS: Preoperative DA was independently associated with AKI in high-risk patients following non-cardiac surgery. Preoperative routine urinalysis for determination of DA status was suggested in early risk stratification.

Effect of low-dose dexmedetomidine on sleep quality in postoperative patients with mechanical ventilation in the intensive care unit: A pilot randomized trial.

Background: Sleep disturbances are prevalent in patients requiring invasive mechanical ventilation in the intensive care unit (ICU) and are associated with worse outcomes. Sedative-dose dexmedetomidine may improve sleep quality in this patient population but is associated with adverse events. Herein, we tested the effect of low-dose dexmedetomidine infusion on nighttime sleep quality in postoperative ICU patients with invasive ventilation. Methods: In this pilot randomized trial, 80 adult patients who were admitted to the ICU after non-cardiac surgery and required invasive mechanical ventilation were randomized to receive either low-dose dexmedetomidine (0.1 to 0.2 µg/kg/h, n = 40) or placebo (n = 40) for up to 72 h. The primary endpoint was overall subjective sleep quality measured using the Richards-Campbell Sleep Questionnaire (score ranges from 0 to 100, with a higher score indicating better quality) in the night of surgery. Secondary outcomes included sleep structure parameters monitored with polysomnography from 9:00 PM on the day of surgery to the next 6:00 AM. Results: All 80 patients were included in the intention-to-treat analysis. The overall subjective sleep quality was median 52 (interquartile 20, 66) with placebo vs. 61 (27, 79) with dexmedetomidine, and the difference was not statistically significant (median difference 8; 95% CI: -2, 22; P = 0.120). Among 68 patients included in sleep structure analysis, those in the dexmedetomidine group tended to have longer total sleep time [median difference 54 min (95% CI: -4, 120); P = 0.061], higher sleep efficiency [median difference 10.0% (95% CI: -0.8%, 22.3%); P = 0.060], lower percentage of stage N1 sleep [median difference -3.9% (95% CI: -11.8%, 0.5%); P = 0.090], higher percentage of stage N3 sleep [median difference 0.0% (95% CI: 0.0%, 0.4%); P = 0.057], and lower arousal index [median difference -0.9 (95% CI -2.2, 0.1); P = 0.091] but not statistically significant. There were no differences between the two groups regarding the incidence of adverse events. Conclusion: Among patients admitted to the ICU after surgery with intubation and mechanical ventilation, low-dose dexmedetomidine infusion did not significantly improve the sleep quality pattern, although there were trends of improvement. Our findings support the conduct of a large randomized trial to investigate the effect of low-dose dexmedetomidine in this patient population. Clinical trial registration: ClinicalTrial.gov, identifier: NCT03335527.

PKM2 promotes pulmonary fibrosis by stabilizing TGF-ß1 receptor I and enhancing TGF-ß1 signaling.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease, and the molecular mechanisms remain poorly understood. Our findings demonstrated that pyruvate kinase M2 (PKM2) promoted fibrosis progression by directly interacting with Smad7 and reinforcing transforming growth factor-ß1 (TGF-ß1) signaling. Total PKM2 expression and the portion of the tetrameric form elevated in lungs and fibroblasts were derived from mice with bleomycin (BLM)-induced pulmonary fibrosis. Pkm2 deletion markedly alleviated BLM-induced fibrosis progression, myofibroblast differentiation, and TGF-ß1 signaling activation. Further study showed that PKM2 tetramer enhanced TGF-ß1 signaling by directly binding with Smad7 on its MH2 domain, and thus interfered with the interaction between Smad7 and TGF-ß type I receptor (TßR1), decreased TßR1 ubiquitination, and stabilized TßR1. Pharmacologically enhanced PKM2 tetramer by TEPP-46 promoted BLM-induced pulmonary fibrosis, while tetramer disruption by compound 3k alleviated fibrosis progression. Our results demonstrate how PKM2 regulates TGF-ß1 signaling and is a key factor in fibrosis progression.

Association between urine microscopy and severe acute kidney injury in critically ill patients following non-cardiac surgery: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and adverse complication following non-cardiac surgery. Evidence have shown urine microscopy could help early detection, differentiating the causes and predicting the progression of AKI. However, little evidence is available on AKI after non-cardiac surgery. Thus, we investigated the association between urine microscopy and severe AKI in critically ill patients after non-cardiac surgery. METHODS: This was a single-center prospective cohort study. The primary outcome was severe AKI, defined as stage 2 or 3 according to maximal KDIGO criteria within 7 days following non-cardiac surgery. Urine microscopy immediately, 6 and 12 hours after surgical intensive care unit (SICU) admission were examined and graded by a urine microscopy score (UMS) based on the observed quantification of renal tubular cells and casts in the sediment. Then, multivariate Logistic regression models were used to analyze the associations between UMS and postoperative severe AKI. RESULTS: From May 20, 2019 to November 24, 2020, 661 patients were enrolled with 147 patients (22.2%) developing postoperative severe AKI. Multivariate Logistic regression model showed elevated UMS (≥1) 6 and 12 hours after SICU admission were independently associated with postoperative severe AKI (OR 2.200, 95% CI: 1.182-4.095, P=0.013 and OR 2.949, 95% CI: 1.657-5.248, P<0.001, respectively). Furthermore, higher UMS 6 hours after SICU admission demonstrated correlation with greater risk of severe AKI with OR 3.887 (95% CI: 1.430-10.563) for UMS ≥3 and OR 2.429 (95% CI: 1.237-4.770) for UMS =1-2. The specificity and sensitivity of UMS ≥1 for severe AKI was 93.8% (95% CI: 91.7-95.9%) and 15.6% (95% CI: 9.7-21.5%), respectively. While the negative and positive predictive value was 79.5% (95% CI: 76.3-82.7%) and 41.8% (95% CI: 28.8-54.8%), respectively. In addition, patients with higher UMS (≥3, 1-2 and 0) had significantly more postoperative complications and longer SICU stay; and they also showed a trend toward other adverse postoperative outcomes. CONCLUSIONS: Early urine microscopy was independently associated with severe AKI in critically ill patients following non-cardiac surgery with higher UMS related to greater risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03880110.

Human Amnion Epithelial Cells and Their Derived Exosomes Alleviate Sepsis-Associated Acute Kidney Injury via Mitigating Endothelial Dysfunction.

Background: Sepsis is characterized by organ dysfunction resulting from a patient's dysregulated response to infection. Sepsis-associated acute kidney injury (S-AKI) is the most frequent complication contributing to the morbidity and mortality of sepsis. The prevention and treatment of S-AKI remains a significant challenge worldwide. In the recent years, human amnion epithelial cells (hAECs) have drawn much attention in regenerative medicine, yet the therapeutic efficiency of hAECs in S-AKI has not been evaluated. Methods: Septic mice were induced by cecal ligation and puncture (CLP) operation. hAECs and their derived exosomes (EXOs) were injected into the mice via tail vein right after CLP surgery. The 7-day survival rate was observed. Serum creatinine level was measured and H&E staining of tissue sections were performed 16 h after CLP. Transmission electron microscopy was used to examine the renal endothelial integrity in CLP mice. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) and EXOs. Zonula occludens-1 (ZO-1) localization was observed by immunofluorescence staining. Expression of phosphor-p65 (p-p65), p65, vascular cell adhesion molecule-1 (VCAM-1), and ZO-1 in the kidney were determined by Western blot. Results: hAECs decreased the mortality of CLP mice, ameliorated septic injury in the kidney, and improved kidney function. More precisely, hAECs suppressed systemic inflammation and maintained the renal endothelial integrity in septic animals. EXOs from hAECs exhibited similar renal protective effects as their parental cells. EXOs maintained endothelial cell adhesion junction in vitro and inhibited endothelial cell hyperactivation in vivo. Mechanistically, EXOs suppressed proinflammatory nuclear factor kappa B (NF-κB) pathway activation in LPS-treated HUVECs and in CLP mice kidneys. Conclusion: Our results indicate that hAECs and their derived EXOs may ameliorate S-AKI via the prevention of endothelial dysfunction in the early stage of sepsis in mice. Stem cell or exosome-based therapy targeting endothelial disorders may be a promising alternative for treatment of S-AKI.

Lenalidomide attenuates post-inflammation pulmonary fibrosis through blocking NF-κB signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a pathological consequence of interstitial pulmonary diseases, and is characterized by the persistence of fibroblasts and excessive deposition of extracellular matrix (ECM). The etiology of IPF is multifactorial. Although the role of inflammation in fibrogenesis is controversial, it is still recognized as an important component and epiphenomenon of IPF. Stimulus increase production of pro-inflammatory cytokines and activation of NF-κB, which will further promote inflammation response and myofibroblast transition. Lenalidomide is an immunomodulatory drug. Previous studies have revealed its anti-tumor effects through regulating immune response. Here we investigate the effect of lenalidomide on post-inflammation fibrosis. In vitro study revealed that lenalidomide inhibited NF-κB signaling in LPS-induced macrophage, and further attenuated macrophage-induced myofibroblast activation. Meanwhile, lenalidomide could inhibit TGF-ß1-induced myofibroblast activation through suppressing TGF-ß1 downstream MAPK signaling. In vivo study showed that lenalidomide inhibited pro-inflammatory cytokines TNF-α and IL-6 while enhanced anti-fibrotic cytokines IFN-γ and IL-10 in bleomycin-induced inflammation model, and attenuated pulmonary fibrosis and collagen deposition in the following fibrosis stage. In conclusion, our results demonstrate that lenalidomide possesses potential anti-fibrotic effects through suppressing NF-κB signaling.

Detection of Candida DNA in peritoneal fluids by PCR assay optimizing the diagnosis and treatment for intra-abdominal candidiasis in high-risk ICU patients: A prospective cohort study.

Background: Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in critically ill patients. This study aimed to investigate whether the polymerase chain reaction (PCR) assay for detecting Candida DNA in peritoneal fluids (PF) is useful in diagnosing and management of IAC in high-risk patients in intensive care unit (ICU). Methods: A prospective single-center cohort study of surgical patients at high risk for IAC was conducted in the ICU. PF was collected from the abdominal drainage tubes (within 24 h) or by percutaneous puncture. Direct PF smear microscopy, PF culture, blood culture, and serum (1-3)-ß-D-glucan were performed in all patients. For Candida PCR assay, the ITS1/ITS4 primers that targeted the ITS1-5.8 s-ITS2 regions were used for PCR, and sequencing analysis was used to identify the pathogen at the species level. IAC was defined according to the 2013 European consensus criteria. Results: Among 83 patients at high risk for IAC, the IAC criteria were present in 17 (20.5%). The sensitivity and specificity of the Candida PCR assay were 64.7 and 89.4%, respectively, and the area under the receiver operating characteristic curve was 0.77 (95% CI: 0.63-0.91). In this cohort, the positive predictive value and negative predictive value were 90.8% (95% CI: 80.3-96.2%) and 61.1% (95% CI: 36.1-81.7%), respectively. Diagnostic consistency was moderate (kappa 0.529, p < 0.001) according to the 2013 European consensus criteria. Conclusion: Detection of Candida DNA in PF using PCR can be considered an adjunct to existing routine diagnostic tools which may optimize the diagnosis and antifungal treatment of IAC in high-risk patients in the ICU.

Prevention of deep venous thrombosis in patients undergoing knee arthroplasty by intermittent pneumatic compression apparatus.

OBJECTIVE: This study discussed and analyzed the preventive value of intermittent pneumatic compression combined with early rehabilitation training for deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA). METHODS: During January 2019 to April 2020, 85 patients who underwent TKA in our hospital were selected as subjects, and were randomly divided into an observation group (n=44) and control group (n=41) by table of random numbers. The control group patients received conventional nursing care after TKA surgery, while the observation group received combinative treatment of intermittent pneumatic compression therapy and early rehabilitation training like the conventional treatment in the control group. Subsequently, the circumference and mobility of knee joint, hemorrheologic indexes and the incidence of DVT between the two groups of patients before and after surgery were compared. RESULTS: The knee circumferences of the two groups on 3 d and 7 d preoperatively were higher than 1 d before surgery (P<0.05), and the indexes of the observation group on 3 d and 7 d preoperatively were lower than that of the control group (P<0.05). The range of motion (ROM) of the two groups 3 d postoperatively were higher than that before surgery (P<0.05), the ROM in observation group 7 d postoperatively was increased than 3 d postoperatively (P<0.05), and the observation group had higher ROM on 3 d and 7 d postoperatively than that of control group (P<0.05). The two groups of patients had insignificant difference in knee function before treatment (P>0.05); the knee function of the two groups after treatment was better than pretreatment (P<0.05), and the observation group was better than the control group (P<0.05). The observation group had lower DVT incidence than the control group (P<0.05). CONCLUSION: Combinative treatment of intermittent pneumatic compression and early rehabilitation training can effectively improve the postoperative knee function of patients undergoing TKA, promote recovery, and effectively prevent DVT. In conclusion, the combinative treatment is worthy of clinical application.

Clevudine attenuates bleomycin-induced early pulmonary fibrosis via regulating M2 macrophage polarization.

Pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease. It is a growing clinical problem which can result in breathlessness or respiratory failure and has an average life expectancy of 3 years from diagnosis. Predominantly accumulation of M2 macrophages accelerates fibrosis progression by secreting multiple cytokines that promote fibroblast to myofibroblast transition and aberrant wound healing of epithelial cells. Targeting activated macrophages to inhibit the pro-fibrotic phenotype is considered as an approach for the potential treatment of PF. Clevudine is s a purine nucleoside analogue which in an oral formulation is approved for treatment of patients with hepatitis B virus (HBV). Here, we found that clevudine is capable of suppressing pro-fibrotic phenotype (i.e., CD206, Arg1 and YM1) of M2 macrophages while enhancing anti-fibrotic phenotype (i.e., CD86, IL-6 and IL-10) by inhibiting PI3K/Akt signaling pathway. This effect further alleviates M2-induced myofibroblast activation and epithelial-to-mesenchymal transition (EMT), thus resulting in a decline of collagen deposition, pro-fibrotic cytokines secretion, with a concomitant recover ofpulmonary functions in vivo. Less infiltration of M2 macrophages between α-SMA + cells was also found in clevudine treated mice. Our findings indicate a potential anti-fibrotic effect of clevudine by regulating macrophage polarization and might be meaningful in clinical settings.

[Relationship between postoperative immediate serum albumin level and postoperative acute kidney injury after major abdominal surgery in critically ill patients].

OBJECTIVE: To investigate the relationship between albumin (ALB) level immediately after major abdominal surgery and postoperative acute kidney injury (AKI) in critically ill patients. METHODS: A retrospective cohort study was conducted. Patients who accepted the major abdominal surgery admitted to the department of intensive care unit (ICU) of the Peking University First Hospital from June 2017 to July 2018 were enrolled. Clinical data including the postoperative ALB level and renal function were collected. Patients were divided into postoperative AKI group and postoperative non-AKI group according to the AKI diagnosis and staging criteria of Kidney Disease: Improving Global Outcomes (KIDGO). The risk factors of perioperative AKI occurrence were analyzed, and multivariate Logistic regression analysis was performed. The receiver operator characteristic curve (ROC curve) was plotted for the ALB level to predict the occurrence of AKI and to determine the ALB cut-off value. The Kaplan-Meier survival curve of postoperative survival of patients was drawn. RESULTS: A total of 363 critically ill patients underwent major abdominal surgery, and 105 patients (28.9%) suffered from AKI. Compared with the non-AKI group, the patients in the AKI group were older (t = -2.794, P = 0.005), preoperative proportions of diabetes and chronic kidney disease were higher (χ21 = 4.613, χ22 = 5.427, both P < 0.05), the proportion of American Society of Anesthesiologists (ASA) grades and V was higher (χ2 = 19.444, P < 0.001), baseline serum creatinine (SCr) and preoperative brain natriuretic peptide (BNP) levels were higher (U1 = 2.859, U2 = 2.283, both P < 0.05), preoperative ALB level was lower (t = 3.226, P = 0.001), the proportion of preoperative use of contrast media was higher (χ2 = 7.431, P = 0.006), the proportions of emergency surgery and using vasopressor during surgery were higher (χ21 = 4.211, χ 22 = 4.947, both P < 0.05), non-renal SOFA score and acute physiology and chronic health evaluation (APACHE) within 24 hours after ICU admission were higher (U = 2.233, t = 3.130, both P < 0.05), and the proportion of postoperative immediate ALB less than 32 g/L was higher (χ2 = 7.601, P = 0.006). ROC curve analysis showed that the cut-off value of immediate postoperative ALB for predicting postoperative AKI was 32 g/L, with the sensitivity was 86.7%, and the specificity was 28.3%. Multivariate Logistic regression analysis showed that ASA grade, use of contrast before surgery, baseline SCr and postoperative immediate serum ALB level below 32 g/L were independent risk factors for AKI [odds ratio (OR) and 95% confidence interval (95%CI) were 2.248 (1.458-3.468), 2.544 (1.332-4.857), 1.018 (1.008-1.027) and 2.685 (1.383-5.212), respectively, all P < 0.01]. Compared with the non-AKI group, the proportion of patients with AKI undergoing mechanical ventilation in ICU was higher (χ2 = 13.635, P < 0.001), mechanical ventilation duration, length of ICU stay, postoperative hospital stay were longer (U1 = 2.530, U2 = 5.032, U3 = 3.200, all P < 0.05), more postoperative complications except AKI (U = 4.799, P < 0.001), and in-hospital mortality and total hospitalization cost were higher (χ2 = 11.681, U = 3.537, both P < 0.001). Compared with the group with postoperative immediate serum ALB ≥ 32 g/L, the proportion of mechanical ventilation in ICU of the ALB < 32 g/L group was higher (χ2 = 33.365, P < 0.001), the length of ICU stay and postoperative hospital stay were longer (U1 = 3.246, U2 = 4.563, both P < 0.001), more postoperative complications except AKI (U = 3.328, P = 0.001), total hospitalization cost was higher (U = 4.127, P < 0.001). CONCLUSIONS: For critically ill patients underwent major abdominal surgery, the postoperative immediate serum ALB level below 32 g/L significantly increased the risk of AKI, which was related to the poor prognosis of the patients.

Effect of clinical decision support systems on clinical outcome for acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Clinical decision support systems including both electronic alerts and care bundles have been developed for hospitalized patients with acute kidney injury. METHODS: Electronic databases were searched for randomized, before-after and cohort studies that implemented a clinical decision support system for hospitalized patients with acute kidney injury between 1990 and 2019. The studies must describe their impact on care processes, patient-related outcomes, or hospital length of stay. The clinical decision support system included both electronic alerts and care bundles. RESULTS: We identified seven studies involving 32,846 participants. Clinical decision support system implementation significantly reduced mortality (OR 0.86; 95 % CI, 0.75-0.99; p = 0.040, I2 = 65.3 %; n = 5 studies; N = 30,791 participants) and increased the proportion of acute kidney injury recognition (OR 3.12; 95 % CI, 2.37-4.10; p < 0.001, I2 = 77.1 %; n = 2 studies; N = 25,121 participants), and investigations (OR 3.07; 95 % CI, 2.91-3.24; p < 0.001, I2 = 0.0 %; n = 2 studies; N = 25,121 participants). CONCLUSIONS: Nonrandomized controlled trials of clinical decision support systems for acute kidney injury have yielded evidence of improved patient-centered outcomes and care processes. This review is limited by the low number of randomized trials and the relatively short follow-up period.

The complete chloroplast genome of Rhodobryum laxelimbatum (Hampe ex Ochi) Z. Iwatsuki and T. J. Koponen.

Rhodobryum laxelimbatum (Bryophyta, Bryaceae) is one of the folk medicine resources in Southwest China, which has excellent potential for application in treating cardiovascular diseases. In this study, R. laxelimbatum was sequenced by high-throughput sequencing technology. The complete chloroplast genome is 124,632 bp in length with a quadripartite structure. Two inverted repeat regions are 9837 bp, separated by a large single copy region of 86,444 bp and a small single copy region of 18,514 bp. It encodes 118 unique genes, including 82 protein-coding genes, 32 tRNA genes, and four rRNA genes. The phylogenetic tree was constructed based on the complete chloroplast genome sequences of 18 bryophytes, downloaded from GenBank and acquired in this study. The phylogenetic analysis strongly indicated that R. laxelimbatum was the sister group of the clade which consists of Mnium marginatum, Pohlia cruda and Pohlia nutans. The R. laxelimbatum chloroplast genome sequence provides new genomic resources, which will improve its research, conservation, and application in the future.