Shuangling Li

Background: Bloodstream infections (BSI) in intensive care unit (ICU) patients are associated with high morbidity and mortality, necessitating rapid and accurate pathogen identification to guide early antimicrobial therapy. However, traditional blood culture (BC) is limited by the long turnaround time and low sensitivity. Metagenomic next-generation sequencing (mNGS) has been applied in infectious disease diagnostics, but its clinical utility for perioperative ICU patients with BSI requires further evaluation. Methods: This post-hoc analysis included 219 perioperative ICU patients (from a prospective, multi-center cohort, July 2020–June 2023) who underwent concurrent mNGS and BC testing. The study compared pathogen detection differences between the two methods, and evaluated the diagnostic value of mNGS for clinical BSI based on mNGS-assisted clinical diagnostic criteria. Additionally, the impact of mNGS findings on clinical antimicrobial management was assessed. Results: mNGS demonstrated a higher overall pathogen detection rate than BC in the 219 enrolled patients (25.1% vs. 9.6%, p < 0.001), with significant advantages in detecting Gram-negative bacteria (13.2% vs. 5.9%, p = 0.009), anaerobes (3.6% vs. 0.5%, p = 0.018), and fungi (6.4% vs. 0.9%, p = 0.002). Mixed-pathogen infections were identified in 20% of mNGS-positive clinical BSI cases, whereas BC-positive cases exclusively had single-pathogen infections. Ultimately, 64 patients (29.2%) were diagnosed with clinical BSIs. The sensitivity and specificity of the mNGS were 85.9% (95% CI: 74.5%–93.0%), and 80.6% (95% CI: 73.4%–86.4%), respectively, and the area under the receiver operating characteristic curve was 0.833 (95% CI: 0.772–0.894). The positive predictive value and negative predictive value were 64.7% (95% CI: 53.5%–74.6%) and 93.3% (95% CI: 87.3%–96.7%), respectively. Additionally, mNGS led to a positive impact in 56 patients (25.6%), manifested by the identification of new pathogens and guidance for targeted therapy, a negative impact in 11 patients (5.0%), and no clinical impact in 152 patients (69.4%). Conclusions: For perioperative ICU patients, mNGS demonstrated superior pathogen detection rates, broader microbial spectrum coverage, and enhanced polymicrobial infection detection capability versus BC. mNGS exhibited high diagnostic value for clinical BSI, with the potential to facilitate targeted antimicrobial therapy adjustments.

Background: Postoperative risk stratification for severe acute kidney injury (AKI) can facilitate timely intervention and improve prognosis. Objectives: This study aimed to evaluate the added predictive ability of urinary calprotectin for postoperative risk stratification of severe AKI in non-cardiac surgery patients. Design: A total of 580 patients were enrolled, and 98 (17%) developed severe AKI with a median time of 12.8 hours after SICU admission. Methods: In a prospective cohort of patients transferred to the surgical intensive care unit (SICU) after non-cardiac surgery, calprotectin was measured in urine samples collected 0, 6, and 12 hours after SICU admission. A clinical model for predicting severe AKI was established. We tested the ability of urinary calprotectin alone to predict severe AKI by area under the receiver operating characteristics curve (AUC) analysis. We further evaluated the improvement of the pre-diction ability after adding urinary calprotectin in the clinical model by the increment in AUC, relevant integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: Higher urinary calprotectin levels were observed in the severe AKI group at any time point (All P<0.001). In the entire cohort, the AUC of urinary calprotectin at SICU admission for predicting severe AKI was 0.701(95% CI, 0.649 to 0.754), and calprotectin ≥32.3 ng/ml was associated with increased risk (OR 6.119, 95% CI 3.259 – 11.488). The AUC of the clinical model increased from 0.693 (95%CI, 0.633 to 0.754) to 0.730 (95%CI, 0.677 to 0.784) upon adding urinary calprotectin, the NRI was 0.337 (P<0.001) and the IDI was 0.055 (P<0.001). Conclusion: A combination of urinary calprotectin and clinical features could be useful for postoperative risk stratification of severe AKI in non-cardiac surgery patients.

BACKGROUND: The Simple Postoperative AKI Risk (SPARK) index is a novel model for predicting risk of postoperative acute kidney injury (PO-AKI) among patients after noncardiac surgery. However, the performance of the index has been inconsistent partly due to heterogeneity in case mix and effects of the involved clinical features. To clarify potential reasons for poor performance, we tested the SPARK index in a cohort of high-risk patients requiring intensive care unit (ICU) care after noncardiac surgery and examined whether model modification by refitting coefficients of clinical features could optimize model performance. METHODS: This was a single-center prospective cohort study. Preoperative variables of the SPARK index were extracted from electronic medical records. PO-AKI was defined by an increase in sCr ≥26.5 mmol/L within 48 hours or 150% compared with the preoperative baseline value within 7 days after surgery, whereas critical AKI was defined as AKI stage 2 or greater and/or any AKI connected to postoperative death or requiring renal replacement therapy during the hospital stay. Discrimination was evaluated by the area under the receiver operating characteristic curve (AUC), and calibration was evaluated by the Hosmer–Lemeshow χ² test and calibration plot. Model modification was performed by rebuilding the model with the original variables of the SPARK index through proportional odds logistic regression among participants in the earlier study period and was validated in the later one. RESULTS: A total of 973 patients were enrolled, among whom 79 (8.1%) PO-AKI cases and 14 (1.4%) critical AKI cases occurred. Our study participants demonstrated a higher SPARK risk score than the SPARK discovery cohort (eg, 8.02% vs 1.20% allocated in the highest risk group), and the incidence of both outcomes increased through the classes of the score (incidence proportion of PO-AKI increased from 2.56% in the lowest risk group to 25.64% in the highest risk group). The AUCs for PO-AKI and critical AKI were 0.703 (95% confidence interval [CI], 0.641–0.765) and 0.699 (95% CI, 0.550–0.848), respectively. The sensitivity, specificity, negative predictive value and positive predictive value were 68.35%, 57.49%, 95.36%, and 12.44%, respectively, when using 10% of predicted probability of PO-AKI as threshold. Calibration plots suggested acceptable consistency between the predicted and actual risk. After model modification, external validation demonstrated a significantly improved AUC for PO-AKI. CONCLUSIONS: The SPARK index showed fair discrimination and calibration among patients admitted to the ICU after noncardiac surgery. Modification of the model improved the performance of the model in terms of predicting PO-AKI.

To observe the effects of enhanced rehabilitation on the prognosis of critically ill patients in the intensive care unit (ICU). A single-center retrospective historical controlled study was conducted, patients admitted to the ICU of Peking University First Hospital from May 1, 2020, to April 30, 2021, and from October 1, 2021, to September 30, 2022 were enrolled. According to the different rehabilitation treatment strategies during different periods, patients were divided into the conventional rehabilitation group (patients receiving conventional rehabilitation treatment from May 1, 2020, to April 30, 2021) and the enhanced rehabilitation group (patients receiving the therapy of multidisciplinary team, ie medical care-rehabilitation-nursing care from October 1, 2021, to September 30, 2022). General data, acute physiology and chronic health evaluation II (APACHE II), and study endpoints were collected. Primary endpoints included rehabilitation-therapy rate, intervention time for rehabilitation, rehabilitation-related adverse events, and prognostic indicators such as (length of stay in hospital, length of stay in the ICU, and duration of mechanical ventilation). Secondary endpoints included incidence of deep vein thrombosis and hospital mortality. Kaplan-Meier curves were used to analyze cumulative discharge rates within 50 days. A total of 539 ICU patients were enrolled, with 245 in the conventional rehabilitation group and 294 in the enhanced rehabilitation group; 322 patients had an APACHE II score ≤ 15, while 217 patients had an APACHE II score > 15. Compared to the conventional rehabilitation group, the enhanced rehabilitation group demonstrated significantly higher rehabilitation-therapy rate [51.70% (152/294) vs. 11.43% (28/245)], earlier intervention time for rehabilitation [days: 2.00 (1.00, 3.00) vs. 4.00 (3.00, 7.00)]; shorter length of stay in hospital [days: 18.00 (12.00, 30.00) vs. 21.00 (13.00, 36.00)] and lower incidence of DVT [17.01% (50/294) vs. 24.08% (59/245)]. The differences were all statistically significant (all P < 0.05). There were no rehabilitation-related adverse events occurred in either group. Kaplan-Meier analysis demonstrated a significantly higher cumulative discharge rate within 50 days in the enhanced rehabilitation group compared to the conventional rehabilitation group [86.7% (255/294) vs. 82.9% (203/245); Log-Rank test: χ² = 4.262, P = 0.039]. Subgroup analysis showed that for patients with APACHE II score ≤ 15, the enhanced rehabilitation subgroup had higher rehabilitation-therapy rate [44.32% (78/176) vs. 6.16% (9/146), P < 0.05]. For patients with APACHE II score > 15, compared to the conventional rehabilitation group, the enhanced subgroup demonstrated higher rehabilitation-therapy rate [62.71% (74/118) vs. 19.19% (19/99), P < 0.05] and shorter length of stay in hospital [days: 20.50 (12.00, 31.25) vs. 26.00 (16.00, 43.00), P < 0.05]. Enhanced rehabilitation therapy with medical care, rehabilitation and nursing care, improved rehabilitation-therapy rate, advanced time of rehabilitation treatment, reduced length of stay in hospital and incidence of deep vein thrombosis in critically ill patients, particularly benefited those with APACHE II score > 15. The enhanced rehabilitation was beneficial to the patient in the intensive care unit with safety and worth more investigation.

This study reports the diagnosis and treatment of a 26-year-old pregnant woman with severe malnutrition combined with acute pyelonephritis causing sepsis, refractory septic shock and multiple organ failure. A female patient, 26 years old, was admitted to hospital mainly due to "menelipsis for more than 19 weeks, nausea and vomiting for 20 days, fever with fatigue for 3 days". At the end of 19 weeks of intrauterine pregnancy, the patient presented with fever accompanied by urinary tract irritation. Laboratory tests showed elevated inflammatory indicators, and ultrasonography showed bilateral pelvicalyceal dilation. She was diagnosed with acute pyelonephritis, sepsis, acute kidney injury (AKI) and severe malnutrition. After a whole-hospital consultation, the patient was treated with meropenem and vancomycin as antimicrobial therapy, and bilateral nephrostomy drainage was performed simultaneously. After that, the patient suffered a sudden decrease in blood pressure, blood oxygen saturation, and rapid heart rate. Septic shock with multiple organ dysfunction was considered, and she was transferred to intensive care unit (ICU) immediately. After the patient was transferred to ICU, emergency tracheal intubation and ventilator-assisted ventilation were performed. Rapid fluid resuscitation was administered for the patient. While pulse indicator continuous cardiac output (PICCO) monitoring was performed, norepinephrine, terlipressin, and methylene blue were administered to maintain peripheral vascular resistance. Since the patient developed septic cardiomyopathy and cardiogenic shock later, levosimendan and epinephrine were admi-nistered to improve cardiac function. While etiological specimens were delivered, meropenem, teicoplanin and caspofungin were given as initial empiric antimicrobial therapy. Unfortunately, the intrauterine fetal death occurred on the night of admission to ICU. On the 3rd day of ICU admission, a still-born child was delivered vaginally with 1/5 defect of the fetal membrane. On the 6th day of ICU admission, the patient had fever again with elevated inflammatory indicators. After excluding infection in other parts, intrau-terine infection caused by incomplete delivery of fetal membrane was considered. Then emergency uterine curettage was performed and the infection gradually improved. Later the laboratory results showed that the nephrostomy drainage was cultured for Escherichia coli and uterine, cervical and vaginal secretions were cultured for Candida albicans. Due to severe infection and intrauterine incomplete abortion, the patient developed disseminated intravascular coagulation (DIC). Active antimicrobial therapy and blood product supplement were given. However, the patient was critically ill with significant decrease in hemoglobin and platelets combined with multiple organ failure. Thrombotic microangiopathy (TMA) was not excluded yet, so plasma exchange was performed for the patient in order not to delay treatment. The patient underwent bedside continuous renal replacement therapy (CRRT) for AKI. The patient was complicated with acute liver injury, and the liver function gradually returned to normal after liver protection, antimicrobial therapy and other treatments. Due to the application of large doses of vasoactive drugs, the extremities of the patient gradually developed cyanosis and ischemic necrosis. Local dry gangrene of the bilateral toes remained at the time of discharge. In general, the patient suffered from septic shock, cardiogenic shock, combined with DIC and multiple organ dysfunction. After infection source control, antimicrobial therapy, uterine curettage, blood purification treatment, nutritional and metabolic support, the patient was discharged with a better health condition.

Background: Transcription factor Krüppel-like factor 3 (KLF3) may be involved in regulating inflammation and lymphocyte function. Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression. However,... | Find, read and cite all the research you need on Tech Science Press

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. 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. 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]. 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.

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 (C_min), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC_0-24/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 C_min of 15 mg/L and a target AUC_0-24/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 AUC_0-24/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 C_min and AUC, and a single dose of at least 12 mg/kg may be needed. AUC_0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin C_min on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

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)-β-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.