Construction of Quench-Induced Ru-Doped CoNiP Hierarchical Spheres for Hydrogen Evolution at High Current Densities.

Optimizing the electronic configuration improved the electrocatalytic performance of Ru doping. However, efficiently doping Ru and ensuring its stability in the hollow hierarchical structure posed a challenge. This work innovatively utilized the huge temperature difference between calcination and ice water (0 °C) to rapidly dope Ru atoms onto the CoNiP hierarchical spheres. Notably, the Ru-anchored hierarchical spheres enhanced the active area and internal space utilization. In addition, the addition of Ru dopant optimized the electronic structure and hydrogen evolution reaction (HER) kinetics of CoNiP. Surprisingly, Ru-CoNiP only required 250 mV to generate 1 A cm-2, which was 1.5 times that of commercial Pt/C. Moreover, its activation energy (Ea) was 24.3% lower than CoNiP, further confirming that the Ru dopant reduced the energy barrier of alkaline HER. In conclusion, this work proposed a new method for promoting the doping of trace amounts of ruthenium into hierarchical spheres through quenching.

A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway.

Autophagy plays a crucial role in the development and progression of ischemic acute kidney injury (AKI). However, the function and mechanism of circular RNAs (circRNAs) in the regulation of autophagy in ischemic AKI remain unexplored. Herein, we find that circ-ZNF609, originating from the ZNF609 locus, is highly expressed in the kidney after ischemia/reperfusion injury, and urinary circ-ZNF609 is a moderate predictor for AKI in heart disease patients. Overexpression of circ-ZNF609 can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis while inhibiting proliferation in HK-2 cells, which is blocked by silencing circ-ZNF609. Mechanistically, circ-ZNF609 encodes a functional protein consisting of 250 amino acids (aa), termed ZNF609-250aa, the overexpression of which can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis in HK-2 cells in vitro and in AKI kidneys in vivo. The blockade of AKT and mTOR signaling with pharmacological inhibitors is capable of reversing ZNF609-250aa-induced autophagy flux impairment and cell apoptosis in HK-2 cells. The present study demonstrates that highly expressed circ-ZNF609-encoded ZNF609-250aa induces cell apoptosis and AKI by impairing the autophagy flux via an AKT/mTOR-dependent mechanism. These findings imply that targeting circ-ZNF609 may be a novel therapy for ischemic AKI.

The incidence, risk factors and outcomes of acute kidney injury in critically ill patients undergoing emergency surgery: a prospective observational study.

BACKGROUND: Without sufficient evidence in postoperative acute kidney injury (AKI) in critically ill patients undergoing emergency surgery, it is meaningful to explore the incidence, risk factors, and prognosis of postoperative AKI. METHODS: A prospective observational study was conducted in the general intensive care units (ICUs) from January 2014 to March 2018. Variables about preoperation, intraoperation and postoperation were collected. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. RESULTS: Among 383 critically ill patients undergoing emergency surgery, 151 (39.4%) patients developed postoperative AKI. Postoperative reoperation, postoperative Acute Physiology and Chronic Health Evaluation (APACHE II) score, and postoperative serum lactic acid (LAC) were independent risk factors for postoperative AKI, with the adjusted odds ratio (ORadj) of 1.854 (95% confidence interval [CI], 1.091-3.152), 1.059 (95%CI, 1.018-1.102), and 1.239 (95%CI, 1.047-1.467), respectively. Compared with the non-AKI group, duration of mechanical ventilation, renal replacement therapy, ICU and hospital mortality, ICU and hospital length of stay, total ICU and hospital costs were higher in the AKI group. CONCLUSIONS: Postoperative reoperation, postoperative APACHE II score, and postoperative LAC were independent risk factors of postoperative AKI in critically ill patients undergoing emergency surgery.

Combining Serum Cystatin C and Urinary N-Acetyl-Beta-D-Glucosaminidase Improves the Precision for Acute Kidney Injury Diagnosis after Resection of Intracranial Space-Occupying Lesions.

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent and associated with adverse outcomes. Unfortunately, the early diagnosis of AKI remains a challenge. Combining functional and tubular damage biomarkers may provide better precision for AKI detection. However, the diagnostic accuracy of this combination for AKI after neurosurgery is unclear. Serum cystatin C (sCysC) and urinary albumin/creatinine ratio (uACR) are considered functional biomarkers, while urinary N-acetyl-ß-D-glucosaminidase (uNAG) represents tubular damage. We aimed to assess the performances of these clinical available biomarkers and their combinations for AKI prediction after resection of intracranial space-occupying lesions. METHODS: A prospective study was conducted, enrolling adults undergoing resection of intracranial space-occupying lesions and admitted to the neurosurgical intensive care unit. The discriminative abilities of postoperative sCysC, uNAG, uACR, and their combinations in predicting AKI were compared using the area under the receiver operating characteristic curve (AUC-ROC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). RESULTS: Of 605 enrolled patients, AKI occurred in 67 patients. The cutoff values of sCysC, uNAG, and uACR to predict postoperative AKI were 0.72 mg/L, 19.98 U/g creatinine, and 44.21 mg/g creatinine, respectively. For predicting AKI, the composite of sCysC and uNAG (AUC-ROC = 0.785) outperformed either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). Adding this panel to the predictive model improved the AUC-ROC to 0.808. Moreover, this combination significantly improved risk reclassification over the clinical model alone, with cNRI (0.633) and IDI (0.076). Superior performance of this panel was further confirmed with bootstrap internal validation. CONCLUSIONS: Combination of functional and tubular damage biomarkers improves the predictive accuracy for AKI after resection of intracranial space-occupying lesions.

The effect of glucocorticoids on serum cystatin C in identifying acute kidney injury: a propensity-matched cohort study.

BACKGROUND: Glucocorticoids may impact the accuracy of serum cystatin C (sCysC) in reflecting renal function. We aimed to assess the effect of glucocorticoids on the performance of sCysC in detecting acute kidney injury (AKI) in critically ill patients. METHODS: A prospective observational cohort study was performed in a general intensive care unit (ICU). Using propensity score matching, we successfully matched 240 glucocorticoid users with 960 non-users among 2716 patients. Serum creatinine (SCr) and sCysC were measured for all patients at ICU admission. Patients were divided into four groups based on cumulative doses of glucocorticoids within 5 days before ICU admission (Group I: non-users; Group II: 0 mg < prednisone ≤50 mg; Group III: 50 mg < prednisone ≤150 mg; Group IV: prednisone > 150 mg). We compared the performance of sCysC for diagnosing and predicting AKI in different groups using the area under the receiver operator characteristic curve (AUC). RESULTS: A total of 240 patients received glucocorticoid medication within 5 days before ICU admission. Before and after matching, the differences of sCysC levels between glucocorticoid users and non-users were both significant (P <  0.001). The multiple linear regression analysis revealed that glucocorticoids were independently associated with sCysC (P <  0.001). After matching, the group I had significantly lower sCysC levels than the group III and group IV (P <  0.05), but there were no significant differences in sCysC levels within different glucocorticoids recipient groups (P > 0.05). Simultaneously, we did not find significant differences in the AUC between any two groups in the matched cohort (P > 0.05). CONCLUSIONS: Glucocorticoids did not impact the performance of sCysC in identifying AKI in critically ill patients.

C-reactive protein concentration as a risk predictor of mortality in intensive care unit: a multicenter, prospective, observational study.

BACKGROUND: It is not clear whether there are valuable inflammatory markers for prognosis judgment in the intensive care unit (ICU). We therefore conducted a multicenter, prospective, observational study to evaluate the prognostic role of inflammatory markers. METHODS: The clinical and laboratory data of patients at admission, including C-reactive protein (CRP), were collected in four general ICUs from September 1, 2018, to August 1, 2019. Multivariate logistic regression was used to identify factors independently associated with nonsurvival. The area under the receiver operating characteristic curve (AUC-ROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the effect size of different factors in predicting mortality during ICU stay. 3 -knots were used to assess whether alternative cut points for these biomarkers were more appropriate. RESULTS: A total of 813 patients were recruited, among whom 121 patients (14.88%) died during the ICU stay. The AUC-ROC values of PCT and CRP for discriminating ICU mortality were 0.696 (95% confidence interval [CI], 0.650-0.743) and 0.684 (95% CI, 0.633-0.735), respectively. In the multivariable analysis, only APACHE II score (odds ratio, 1.166; 95% CI, 1.129-1.203; P = 0.000) and CRP concentration > 62.8 mg/L (odds ratio, 2.145; 95% CI, 1.343-3.427; P = 0.001), were significantly associated with an increased risk of ICU mortality. Moreover, the combination of APACHE II score and CRP > 62.8 mg/L significantly improved risk reclassification over the APACHE II score alone, with NRI (0.556) and IDI (0.013). Restricted cubic spline analysis confirmed that CRP concentration > 62.8 mg/L was the optimal cut-off value for differentiating between surviving and nonsurviving patients. CONCLUSION: CRP markedly improved risk reclassification for prognosis prediction.

Gingival metastasis from primary hepatocellular carcinoma: a case report and literature review of 30 cases.

BACKGROUND: Gingival metastasis from primary hepatocellular cancer (HCC) is rare, highly malignant, and generally has no distinct symptoms. Not performing a biopsy can lead to misdiagnosis. This article reports an 87-year-old male with gingival metastasis from HCC. To gain a better insight into this disease, we also conducted a literature review of 30 cases and discussed the clinical and pathological characteristics, diagnosis, treatment and prognosis of this unusual form of liver cancer. CASE PRESENTATION: An 87-year-old man was hospitalized with a chief complaint of chronic constipation and diffuse lower extremity edema. His past medical history included a three-year hepatitis B infection and a cerebral infarction 17 years prior. Imaging examination detected a massive hepatocellular carcinoma in the right liver lobe and multiple metastases in the lungs. Oral examinations revealed a reddish, cherry-sized exophytic mass on the right upper gum. The mass was tentatively diagnosed as a primary gingival tumor and was ultimately confirmed by biopsy as a metastatic carcinoma originating in the liver. The patient decided, with his guardians, to receive palliative care and not to remove the mass. Unfortunately, the patient accidentally bit the mass open; profuse bleeding ensued and local pressure exerted a poor hemostatic effect. The patient's condition worsened, and he eventually died of multiple organ failure. We also performed a literature review and discussed 30 cases of gingival metastases from HCC. The findings indicated that these lesions affected males more than females, with a ratio of 6:1, and infiltrated the upper gingivae (63.1%) more than the lower gingivae (36.7%). Survival analysis indicated that the overall survival for patients with upper gingival metastasis was worse than for those with lower gingival metastasis, and patients receiving treatments for primary liver cancer or metastatic gingival tumors had better overall or truncated survival times. CONCLUSION: Gingival metastasis from primary hepatocellular carcinoma is rare, and its diagnosis has presented challenges to clinicians. To avoid a potential misdiagnosis, a biopsy is mandatory regardless of whether a primary cancer is located. Early diagnosis and treatment for primary liver cancer or metastatic gingival lesions may improve survival expectations.

Impact of thyroid function on cystatin C in detecting acute kidney injury: a prospective, observational study.

BACKGROUND: Cystatin C (Cys C) used clinically for detecting early acute kidney injury (AKI) was reported to be associated with thyroid function. Therefore, whether the performance of Cys C is affected by thyroid hormones has raised concern in critically ill patients. This study aimed to investigate the impact of thyroid hormones on the diagnostic and predictive accuracy of Cys C for AKI, and hence optimize the clinical application of Cys C. METHODS: A prospective observational study was conducted in the general intensive care units (ICUs). Serum creatinine (SCr), Cys C, and thyroid function were documented for all patients at ICU admission. Patients were separated into five quintiles based on free triiodothyronine (FT3) and total triiodothyronine (TT3), and two categories according to the presence of low T3 syndrome or not. The impact of thyroid function on the performance of Cys C in diagnosing and predicting AKI was assessed by area under the receiver operating characteristic curve (AUC). RESULTS: The AKI incidence was 30.0% (402/1339); 225 patients had AKI upon entry, and 177 patients developed AKI during the subsequent 7 days. The AUCs for Cys C in detecting total AKI, established AKI, and later-onset AKI was 0.753, 0.797, and 0.669, respectively. The multiple linear regression analysis demonstrated that TT3 and FT3 were independently associated with Cys C. Overall, although Cys C did not yield any significant difference in AUCs for detecting AKI among patients with different thyroid hormones, the optimal cut-off value of Cys C to detect AKI was markedly different between patients with and without low T3 syndrome. CONCLUSIONS: The thyroid function had no significant impact on the diagnostic and predictive accuracy of Cys C in detecting AKI in ICU patients. However, the optimal cut-off value of Cys C to detect AKI could be affected by thyroid function.

Impact of blood glucose levels on the accuracy of urinary N-acety-ß-D-glucosaminidase for acute kidney injury detection in critically ill adults: a multicenter, prospective, observational study.

BACKGROUND: The performance of urinary N-acetyl-ß-D-glucosaminidase (uNAG) for the detection of acute kidney injury (AKI) was controversial. uNAG is positively correlated with blood glucose levels. Hyperglycemia is common in the critically ill adults. The influence of blood glucose levels on the accuracy of uNAG in AKI detection has not yet been reported. The present study evaluated the effect of blood glucose levels on the diagnostic accuracy of uNAG to detect AKI. METHODS: A total of 1585 critically ill adults in intensive care units at three university hospitals were recruited in this prospective observational study. uNAG, serum glucose, and glycosylated hemoglobin (HbA1c) were measured at ICU admission. Patients were categorized based on the history of diabetes and blood glucose levels. The performance of uNAG to detect AKI in different groups was assessed by the area under the receiver operator characteristic curve. RESULTS: Four hundred and twelve patients developed AKI, of which 109 patients were severe AKI. uNAG was significantly correlated with the levels of serum glucose (P < 0.001) and HbA1c (P < 0.001). After stratification based on the serum glucose levels, no significant difference was observed in the AUC of uNAG in detecting AKI between any two groups (P > 0.05). Stratification for stress hyperglycemic demonstrated similar results.However, among non-diabetic patients, the optimal cut-off value of uNAG for detecting AKI was higher in stress hyperglycemic patients as compared to those without stress hyperglycemia. CONCLUSIONS: The blood glucose levels did not significantly affect the performance of uNAG for AKI detection in critically ill adults. However, the optimal cut-off value of uNAG to detect AKIwas affected by stress hyperglycemia in non-diabetic patients.

The influence of glycemic status on the performance of cystatin C for acute kidney injury detection in the critically ill.

OBJECTIVE: Serum cystatin C (sCysC) used clinically for detecting early acute kidney injury (AKI) was reported to be independently associated with hemoglobin (HbA1c) levels, diabetes, and prediabetes. We aimed to assess the influence of HbA1c levels, diabetes, or prediabetes on the performance of sCysC for AKI detection in critically ill adults. METHODS: A prospective observational study was conducted in a mixed medical-surgical intensive care unit (ICU). Patients were divided into four quartiles based on levels of HbA1c or serum glucose at ICU admission, respectively. Additionally, patients were stratified into four subgroups according to HbA1c levels and history of diabetes, namely recognized diabetes (previous diagnosis of diabetes), unrecognized diabetes, prediabetes, and normal glycemic status. Comparisons were made using the area under the receiver operator characteristic curve (AUC) for AKI detection, and reassessed after patient stratification by above-mentioned glycemic status. RESULTS: Multivariable linear regression revealed that HbA1c levels and history of diabetes were positively related with sCysC (all p < .05). Although stratification for above-mentioned glycemic status displayed no significant difference between AUC of sCysC (all p > .05), sCysC yielded the highest AUCs for detecting AKI in diabetic patients. Moreover, higher optimal cutoff values of sCysC to detect AKI were observed in patients with versus without diabetes. CONCLUSION: Glycemic status has no significant impact on the accuracy of sCysC for AKI detection in critically ill adults and a higher optimal cutoff value of sCysC for AKI detection should be considered in diabetic patients.

COVID-19 and chronic kidney disease: a bibliometric analysis.

Background: The COVID-19 pandemic has caused over 656 million confirmed cases and over 6.6 million deaths worldwide. Chronic kidney disease (CKD) is considered a high-risk factor for COVID-19; therefore, considerable research has been conducted in this field. Therefore, this study aims to conduct a bibliometric analysis of publications related to COVID-19 and CKD. Methods: Publications were retrieved from the Web of Science Core Collection database on 16 January 2023 and screened based on inclusion criteria. Then the authors used Microsoft Excel and CiteSpace to analyze the included publications from the following seven aspects: countries/regions, institutions, journals, authors, cited references, and keywords. Results: In total, 622 publications were included in the study. The USA has the most publications in this field, followed by China. The Icahn School of Medicine at Mount Sinai and Harvard Medical School had the highest number of publications in the field. Journal of Clinical Medicine had the largest number of publications, and Lancet was the most cited journal. Alberto Ortiz was the author with the largest number of publications, but there were no influential authors in this field. The highly cited references are mainly clinical studies on COVID-19. Research hotspots in this field include end-stage recent disease, cardiovascular disease, kidney metastasis, diabetes Mellitus, acute kidney injury, meta-analysis, and consistent plasma. Conclusions: The USA, China, and some European countries and their institutions are major contributors to these publications. End-stage renal disease, acute kidney injury, kidney transplantation and convalescent plasma are current hot topics in the field.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Local maximum synchrosqueezes form scaling-basis chirplet transform.

In recent years, time-frequency analysis (TFA) methods have received widespread attention and undergone rapid development. However, traditional TFA methods cannot achieve the desired effect when dealing with nonstationary signals. Therefore, this study proposes a new TFA method called the local maximum synchrosqueezing scaling-basis chirplet transform (LMSBCT), which is a further improvement of the scaling-basis chirplet transform (SBCT) with energy rearrangement in frequency and can be viewed as a good combination of SBCT and local maximum synchrosqueezing transform. A better concentration in terms of the time-frequency energy and a more accurate instantaneous frequency trajectory can be achieved using LMSBCT. The time-frequency distribution of strong frequency-modulated signals and multicomponent signals can be handled well, even for signals with close signal frequencies and low signal-to-noise ratios. Numerical simulations and real experiments were conducted to prove the superiority of the proposed method over traditional methods.

Ventilator-associated pneumonia prevention in the Intensive care unit using Postpyloric tube feeding in China (VIP study): study protocol for a randomized controlled trial.

BACKGROUND: Ventilator-associated pneumonia is a challenge in critical care and is associated with high mortality and morbidity. Although some consensuses on preventing ventilator-associated pneumonia are reached, it is still somewhat controversial. Meta-analysis has shown that postpyloric tube feeding may reduce the incidences of ventilator-associated pneumonia, which still desires high-quality evidence. This trial aims to evaluate the efficacy and safety profiles of postpyloric tube feeding versus gastric tube feeding. METHODS/DESIGN: In this multicenter, open-label, randomized controlled trial, we will recruit 924 subjects expected to receive mechanical ventilation for no less than 48 h. Subjects on mechanical ventilation will be randomized (1:1) to receive postpyloric or gastric tube feeding and routine preventive measures simultaneously. The primary outcome is the proportion of patients with at least one ventilator-associated pneumonia episode. Adverse events and serious adverse events will be observed closely. DISCUSSION: The VIP study is a large-sample-sized, multicenter, open-label, randomized, parallel-group, controlled trial of postpyloric tube feeding in China and is well-designed based on previous studies. The results of this trial may help to provide evidence-based recommendations for the prevention of ventilator-associated pneumonia. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2100051593 . Registered on 28 September 2021.

Segmenting Cruise Consumers by Motivation for an Emerging Market: A Case of China.

After around four decades of fast growth, the cruise industry has become the most profitable and dynamic segment in the entire global leisure and tourism sector. Behind this growth is a significant shift in the profile of cruise consumers/passengers/tourists, with growth rates twice as fast as those of other types of tourists. China has become a strategic emerging market for the global cruise industry, quickly developing their cruise reception business and holding about 10% of the market share of global cruisers. In this paper, we examine and categorize various travel motivations of Chinese cruise tourists by means of a questionnaire via factor analysis, mean analysis, and K-cluster analysis. The results of the study indicate that Chinese cruise tourists are primarily encouraged to participate in cruise tourism by the motivational dimensions of family leisure/relaxation, natural and cultural exploration, bond/communication, social respect, tourism shopping, and cruise-promotion information sources. The strongest motivations for Chinese cruise tourists were found to be family leisure/relaxation and natural/cultural exploration. We identify four types of cruisers using the K-means cluster method. We find that for all cruiser demographics, leisure/relaxation is the most important motivational factor. Based on these results, we propose some specific solutions for expanding the customer pool in the Chinese cruise market.

Development and Validation of a Nomogram Incorporating Colloid Osmotic Pressure for Predicting Mortality in Critically Ill Neurological Patients.

Backgrounds: The plasma colloid osmotic pressure (COP) values for predicting mortality are not well-estimated. A user-friendly nomogram could predict mortality by incorporating clinical factors and scoring systems to facilitate physicians modify decision-making when caring for patients with serious neurological conditions. Methods: Patients were prospectively recruited from March 2017 to September 2018 from a tertiary hospital to establish the development cohort for the internal test of the nomogram, while patients recruited from October 2018 to June 2019 from another tertiary hospital prospectively constituted the validation cohort for the external validation of the nomogram. A multivariate logistic regression analysis was performed in the development cohort using a backward stepwise method to determine the best-fit model for the nomogram. The nomogram was subsequently validated in an independent external validation cohort for discrimination and calibration. A decision-curve analysis was also performed to evaluate the net benefit of the insertion decision using the nomogram. Results: A total of 280 patients were enrolled in the development cohort, of whom 42 (15.0%) died, whereas 237 patients were enrolled in the validation cohort, of which 43 (18.1%) died. COP, neurological pathogenesis and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were predictors in the prediction nomogram. The derived cohort demonstrated good discriminative ability, and the area under the receiver operating characteristic curve (AUC) was 0.895 [95% confidence interval (CI), 0.840-0.951], showing good correction ability. The application of this nomogram to the validation cohort also provided good discrimination, with an AUC of 0.934 (95% CI, 0.892-0.976) and good calibration. The decision-curve analysis of this nomogram showed a better net benefit. Conclusions : A prediction nomogram incorporating COP, neurological pathogenesis and APACHE II score could be convenient in predicting mortality for critically ill neurological patients.

Assessment of 17 clinically available renal biomarkers to predict acute kidney injury in critically ill patients.

BACKGROUND: Systematic estimation of renal biomarkers in the intensive care unit (ICU) patients is lacking. Seventeen biomarkers were assessed to predict acute kidney injury (AKI) after admission to ICU. MATERIALS AND METHODS: A prospective, observational study was conducted in the general ICU of Guangdong Provincial People's Hospital. Seventeen serum or urine biomarkers were studied for their abilities alone or in combination for predicting AKI and severe AKI. RESULTS: Of 1498 patients, 376 (25.1%) developed AKI. Serum cystatin C (CysC) showed the best performance for predicting both AKI (area under the receiver operator characteristic curve [AUC] = 0.785, mean square error [MSE] = 0.118) and severe AKI (AUC = 0.883, MSE = 0.06). Regarding biomarkers combinations, CysC plus N-acetyl-ß-d-glucosaminidase-to-creatinine ratio (NAG/Cr) was the best for predicting AKI (AUC = 0.856, MSE = 0.21). At the same time, CysC plus lactic acid (LAC) performed the best for predicting severe AKI (AUC = 0.907, MSE = 0.058). Regarding combinations of biomarkers and clinical markers, CysC plus Acute Physiology and Chronic Health Evaluation (APACHE) II score showed the best performance for predicting AKI (AUC = 0.868, MSE = 0.407). In contrast, CysC plus Multiple Organ Dysfunction Score (MODS) had the highest predictive ability for severe AKI (AUC = 0.912, MSE = 0.488). CONCLUSION: Apart from CysC, the combination of most clinically available biomarkers or clinical markers does not significantly improve the forecasting ability, and the cost-benefit ratio is not economical.

Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study.

PURPOSE: The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients. METHODS: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25-4 mg/L. RESULTS: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function. CONCLUSION: In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.

Establishment and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Tigecycline in Critically Ill Patients.

Utilizing tigecycline-d9 as an internal standard (IS), we establish and validate a simple, effective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative measurement of tigecycline (TGC) in patient plasma. Acetonitrile was used as a precipitant to process plasma samples by a protein precipitation method. The analyte and IS were separated on an HSS T3 (2.1 × 100 mm, 3.5 µm) chromatographic column using isocratic program with a mobile phase comprising of 80% solvent A (water containing 0.1% formic acid (v/v) with 5 mM ammonium acetate) and 20% solvent B (acetonitrile) with a flow rate of 0.3 mL/min. The mass spectrometer, scanning in multireaction monitoring (MRM) mode and using an electrospray ion source (ESI), operated in the positive-ion mode. The ion pairs used for quantitative analysis were m/z 586.4 ⟶ 513.3 and m/z 595.5 ⟶ 514.3 for TGC and the IS, respectively. The range of the linear calibration curve obtained with this approach was 50-5000 ng/ml. Intra- and interbatch precision for TGC quantitation were less than 7.2%, and the accuracy ranged from 93.4 to 101.8%. The IS-normalized matrix effect was 87 to 104%. Due to its high precision and accuracy, this novel method allows for fast quantitation of TGC with a total analysis time of 2 min. This approach was effectively applied to study the pharmacokinetics of TGC in critically ill adult patients.