[Construction and external validation of a risk prediction model for unplanned interruption during continuous renal replacement therapy].

OBJECTIVE: To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model. METHODS: A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect. RESULTS: (1) Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×109/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio (OR) = 3.063, 95% confidence interval (95%CI) was 1.200-7.819], blood purification catheter function (OR = 4.429, 95%CI was 1.270-15.451), blood flow rate (OR = 0.928, 95%CI was 0.900-0.957), and frequency of blood pump stops (OR = 1.339, 95%CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95%CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. (2) External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95%CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. CONCLUSIONS: The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.

Diagnostic value of HPV E6/E7 mRNA in screening for cervical intraepithelial neoplasia grade 2 or worse: A systematic review and meta­analysis.

Histology is considered the gold standard for diagnosing the pathological progress of cervical cancer development, while cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) is the cutoff for intervention in clinical practice. The diagnostic value of human papillomavirus (HPV) E6/E7 mRNA in screening for CIN2+ has not been systematically summarized. A meta-analysis was conducted as part of the present study conducted to explore the diagnostic value of HPV E6/E7 mRNA in screening for CIN2+, aiming to provide a new marker for earlier clinical diagnosis of cervical cancer. The PubMed, Embase and Cochrane Library databases were searched from inception to May 2023. Studies reporting the true positive, false positive, true negative and false negative values in differentiating between CIN2+ and CIN2- were included, while duplicate publications, studies without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews and systematic reviews were excluded. STATA software was used to analyze the data. A total of 2,224 patients were included of whom there were 1,274 patients with CIN2+ and 950 patients with CIN2-. The pooled sensitivity and specificity of the studies overall were 0.89 (95% CI, 0.84-0.92) and 0.59 (95% CI, 0.46-0.71), respectively; the positive likelihood ratio (LR) and the negative LR of the studies overall were 2.31 (95% CI, 1.61-3.32) and 0.21 (95% CI, 0.14-0.30), respectively. The pooled diagnostic odds ratio of the studies overall was 11.53 (95% CI, 6.85-19.36). Additionally, the area under the curve was 0.88. The analysis indicated that HPV E6/E7 mRNA has high diagnostic efficacy for CIN2+. HPV E6/E7 mRNA is highly sensitive in the diagnosis of CIN2+, which helps to reduce the rate of missed diagnoses. However, lower specificity may lead to a higher number of misdiagnoses in healthy patients.

Identification of novel biomarkers for sepsis diagnosis via serum proteomic analysis using iTRAQ-2D-LC-MS/MS.

BACKGROUND: Sepsis is a common cause of morbidity and mortality in the ICU patients. Early diagnosis and appropriate patient management is the key to improve the patient survival and to limit disabilities in sepsis patients. This study was aimed to find new diagnostic biomarkers of sepsis. METHODS: In this study, serum proteomic profiles in sepsis patients by iTRAQ2D-LC-MS/MS. Thirty seven differentially expressed proteins were identified in patients with sepsis, and six proteins including ApoC3, SERPINA1, VCAM1, B2M, GPX3, and ApoE were selected for further verification by ELISA and immunoturbidimetry in 53 patients of non-sepsis, 37 patients of sepsis, and 35 patients of septic shock. Descriptive statistics, functional enrichment analysis, and ROC curve analysis were conducted. RESULTS: The level of ApoC3 was gradually decreased among non-sepsis, sepsis, and septic shock groups (p = 0.049). The levels of VCAM1 (p = 0.010), B2M (p = 0.004), and ApoE (p = 0.039) were showing an increased tread in three groups, with the peak values of B2M and ApoE in the sepsis group. ROC curve analysis for septic diagnosis showed that the areas under ROC curve (AUC) of ApoC3, VCAM1, B2M, and ApoE were 0.625, 0.679, 0.581, and 0.619, respectively, which were lower than that of PCT (AUC 0.717) and CRP (AUC 0.706), but there were no significant differences between each index and PCT or CRP. The combination including four validated indexes and two classical infection indexes for septic diagnosis had the highest AUC-ROC of 0.772. CONCLUSION: Proteins of ApoC3, VCAM1, B2M, and ApoE provide a supplement to classical biomarkers for septic diagnosis.

Impact of chronic respiratory diseases on re-intubation rate in critically ill patients: a cohort study.

Chronic respiratory diseases' (CRDs) impact on re-intubation rate remains unclear. We investigated the association between these factors in mechanically ventilated patients. Data were extracted from the freely available online Medical Information Mart for Intensive Care III database. CRDs were defined according to ICD-9 codes. Generalised linear regression and propensity score matching were performed. Of 13,132 patients, 7.9% required re-intubation. Patients with chronic obstructive pulmonary disease (COPD) had higher re-intubation (OR 2.48, 95% CI 1.83-3.33) and mortality rates (OR 1.64, 95% CI 1.15-2.34) than those without. Patients with asthma had a lower mortality rate (OR 0.63, 95% CI 0.43-0.92) but a similar re-intubation rate to those of patients without. These findings remained stable after propensity score matching and bootstrapping analysis. The association of COPD with re-intubation was significantly stronger in patients with high oxygen-partial pressure (PaO2) or mild disease severity but was independent of carbon dioxide partial pressure. Corticosteroid use was associated with increased re-intubation rates in subgroups without CRDs (OR 1.77-1.99, p < 0.001) but not in subgroups with CRDs. COPD patients with high post-extubation PaO2 or mild disease severity should be carefully monitored as they have higher re-intubation and mortality rates.

[Study on the value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 and growth differentiation factor-15 in the diagnosis of sepsis: test results from the patients of a multicenter study].

OBJECTIVE: To investigate the diagnostic value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 (FAHD1) and growth differentiation factor-15 (GDF-15) in sepsis. METHODS: Based on the database of the whole process of sepsis early warning, diagnosis and treatment management, which was established on the study of sepsis early warning and standardized diagnosis and treatment system, adult patients with suspected infection admitted to the department of critical care medicine of Zhejiang Hospital, Second Affiliated Hospital of Zhejiang University, the First Affiliated Hospital of Sun Yat-Sen University, West China Hospital of Sichuan University, Ningbo First Hospital from May 2014 to October 2015 were enrolled. The basic vital signs, and the main blood routine results, liver and kidney function, blood gas, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score at the time of diagnosis of patients with or without sepsis were analyzed. The preserved serum samples were taken, the levels of procalcitonin (PCT), C-reactive protein (CRP) were detected by electrochemiluminescence method, immunoturbidimetry respectively, and FAHD1 and GDF-15 were detected by enzyme linked immunosorbent assay (ELISA). Univariate and multivariate Logistic regression were used to analyze the risk factors for sepsis diagnose. The indexes' diagnostic efficacy in sepsis were analyzed by receiver operating characteristics curve (ROC curve). RESULTS: A total of 132 patients were enrolled, including 76 cases of sepsis and 56 cases of non-sepsis. Compared with the non-sepsis group, the heart rate in the sepsis group was increased (bpm: 116.4±17.8 vs. 97.4±19.1), while the mean arterial pressure (MAP), platelet count (PLT), arterial partial pressure of oxygen (PaO2) were significantly decreased [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.8±9.7 vs. 74.7±10.3, PLT (×109/L): 120 (69, 204) vs. 163 (117, 239), PaO2 (mmHg): 83.0 (66.6, 108.0) vs. 108.0 (84.4, 130.0), all P < 0.05], direct bilirubin (DBil), serum creatinine (SCr), lactic acid (Lac), APACHE II score and SOFA score were significantly increased [DBil (µmol/L): 13.00 (5.55, 55.31) vs. 6.20 (2.20, 21.90), SCr (µmol/L): 118.00 (70.00, 191.73) vs. 77.20 (59.65, 110.86), Lac (mmol/L): 2.90 (1.50, 4.10) vs. 1.90 (1.20, 2.80), APACHE II score: 20.0 (16.0, 25.0) vs. 16.0 (10.0, 21.0), SOFA score: 12.0 (8.0, 16.0) vs. 8.0 (5.0, 13.0), all P < 0.05]. In addition, the serum levels of FAHD1, GDF-15, PCT and CRP in sepsis group were significantly higher than those in non-sepsis group [FAHD1 (µg/L): 3.96 (2.25, 5.92) vs. 2.47 (1.03, 3.54), GDF-15 (µg/L): 8.46 (4.37, 19.68) vs. 4.32 (1.74, 10.39), PCT (µg/L): 3.79 (1.37, 11.32) vs. 0.42 (0.12, 2.14), CRP (mg/L): 154.43 (61.33, 283.20) vs. 65.95 (28.15, 144.69), all P < 0.01]. Multivariate Logistic regression showed that serum FAHD1 [odds ratio (OR) = 1.135, 95% confidence interval (95%CI) was 1.045-1.234], GDF-15 (OR = 1.090, 95%CI was 1.029-1.155) and CRP (OR = 1.007, 95%CI was 1.002-1.011) were risk factors for sepsis (all P < 0.05). ROC curve analysis of sepsis showed that the areas under ROC curve (AUC) of serum mitochondrial associated proteins FAHD1 and GDF-15 were 0.727 (95%CI was 0.641-0.802) and 0.677 (95%CI was 0.588-0.757), respectively; and the AUC of classical infection indexes PCT and CRP were 0.767 (95%CI was 0.683-0.837) and 0.680 (95%CI was 0.59-0.760), respectively. There was no significant difference between the AUC of mitochondrial associated proteins and classical infection indexes. The combination of FAHD1, GDF-15, PCT and CRP had the largest AUC, which was 0.809 (95%CI was 0.730-0.874), and the sensitivity was 75.00%, and the specificity was 80.00%. CONCLUSIONS: Mitochondrial associated protein FAHD1 and GDF-15 are associated with sepsis, and the diagnostic efficiency is improved when combined with PCT and CRP, which might provide experimental basis for screening diagnostic markers of sepsis.

Fluid intake-related association between urine output and mortality in acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. METHODS: This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. RESULTS: In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98-0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69-0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03-0.253, P <  0.001); this association was not significant for patients with UO/FI ratios > 0.5 (OR: 1.04, 95% CI: 0.96-1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96-0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. CONCLUSIONS: The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

Diagnostic efficacy of serum procalcitonin, C-reactive protein concentration and clinical pulmonary infection score in Ventilator-Associated Pneumonia.

OBJECTIVE: The aim of this study was to evaluate the diagnostic efficacy of serum procalcitonin (PCT), c-reactive protein (CRP) concentration and clinical pulmonary infection score(CPIS) in ventilator-associated pneumonia(VAP). METHODS: Forty-nine patients who were admitted to the intensive care unit (ICU) of Zhejiang Hospital with suspected VAP were recruited in this study. The serum level of PCT and CRP of all patients were measured and CPIS was calculated at the time of VAP suspected diagnosis. Of the included 49 patients, 24 were finally confirmed of VAP by microbiology assay. And the other 25 patients were considered as clinical suspected VAP without microbiology confirmation. The diagnostic sensitivity, specificity and area under the receiver operating characteristic (ROC) curve (AUC) were calculated using the serum PCT, CRP concentration and CPIS. The correlation among serum PCT, CRP concentration and CPIS were also evaluated by Spearson correlation test. RESULTS: A total of 100 bronchoscopic aspiration sputum specimen were examined in bacterial culture. 30 samples were found with suspected pathogenic bacteria. Six samples were found with 2 types of suspected pathogenic bacteria. PCT serum concentration and CPIS score were significantly different (P<0.05) between the patient group [1.4 (0.68 ∼ 2.24), 6.0 (4.25 ∼ 8.00)] and the control group [0.4 (0.17 ∼ 1.39), 3.0 (1.00 ∼ 5.00)] ; However, the serum CRP [102.8(66.75 ∼ 130.90) vs 86.1(66.95 ∼ 110.10)] was not statistically different between the two groups (P>0.05). A significant correlation was found between serum PCT and CRP concentrations (r=0.55, P<0.01), but not between PCT vs CPIS and CRP vs CPIS (p>0.05). The diagnostic sensitivity, specificity and AUC were 72.0%, 75.0%, 0.81 (0.69 ∼ 0.93) for CPIS; 60.0%, 87.5%, 0.76 (0.62 ∼ 0.90) for PCT and 68.0%, 58.3%, 0.59 (0.43 ∼ 0.76) for CRP. CONCLUSION: PCT serum level and CPIS score are elevated in VAP patients and could therefore represent potential biomarkers for VAP early diagnosis.

[Effect of left ventricular global longitudinal strain on prognosis of septic/septic shock patients: a Meta analysis].

OBJECTIVE: To systematically evaluate the effects of left ventricular global longitudinal strain (GLS) determined by two dimensional speckle tracking imaging technology (2D-STI) and left ventricular ejection fraction (LVEF) on the prognosis of patients with sepsis/septic shock. METHODS: Databases such as the National Library of Medicine PubMed database, Dutch medical abstracts Embase, Cochrane Library, Netherlands Elsevier, Springer and China biomedical literature database (CBMdisc), China National Knowledge Internet (CNKI), Wanfang database, China science and technology journal full-text database, Vip Chinese biomedical journal database were searched from the establishment of literature database to April 2018 to study GLS, LVEF and their relationships with mortality of septic/septic shock patients. The literatures screening and data collecting were independently conducted by two researchers, and the quality of the included literature was evaluated. The sensitivity and heterogeneity analysis were performed with RevMan 5.3 software, and the combined effects were calculated. Funnel plot was used to evaluate publication bias. RESULTS: A total of 6 articles including 5 English articles and 1 Chinese article were enrolled. There were 503 patients, 333 in the survival group and 170 in the death group. The quality of the literature was high, and the Newcastle-Ottawa scale (NOS) score was 8-9. Meta-analysis showed that short-term mortality was associated with higher GLS in patients with sepsis/septic shock [standardized mean difference (SMD) = -0.47, 95% confidence interval (95%CI) = -0.76 to -0.18, Z = 3.16, P = 0.002], and there was no significant difference in LVEF between the survival group and the death group (SMD = 0.18, 95%CI = -0.03-0.39, Z = 1.64, P = 0.10). Sensitivity analysis was carried out for each effect index by removing each document one by one, and the results showed that there was no significant change in the combined effect before and after each document, indicating that the results were stable. The funnel plot showed that the effect points of each literature were roughly in the form of "inverted funnels" with a large symmetric distribution centered on the combined effect, but the number of studies included in this study was too small, so the publication bias could not be completely excluded. CONCLUSIONS: Compared with LVEF, GLS might be a more sensitive indicator for detecting myocardial dysfunction in patients with sepsis/septic shock and might have important predictive value for short-term mortality.

[A model based on random forests in prediction of 28-day prognosis in patients with severe sepsis/septic shock].

OBJECTIVE: To establish a severe sepsis/septic shock prognosis prediction model based on randomize forest law (RF model), and to evaluate the prognostic value of this model for patients with severe sepsis/septic shock. METHODS: 497 patients with severe sepsis/septic shock admitted to intensive care unit (ICU) of Zhejiang Hospital from September 2013 to May 2017 were enrolled. The basic data, vital signs and symptoms, biochemical indexes and blood routine indexes on the 1st, 3rd, 5th day and prognosis were collected. According to the 28-day prognosis, the patients were divided into death group and survival group, and the specific indicators about the prognosis of severe sepsis/septic shock were screened. A RF model was constructed by using the specificity indicators. The assessment effectiveness of RF model, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II) were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In 497 cases of severe sepsis/septic shock, 201 cases died, 28-day mortality was 40.4%. (1) According to the index difference of death group and survival group, 19 specific parameters of the RF model were selected, which included the age; 24-hour urine output, urea nitrogen (BUN), serum creatinine (SCr), platelet count (PLT) on the 1st day; heart rate (HR), mean arterial pressure (MAP), cyanosis and clammy skin on the 3rd day; temperature, HR, MAP, 24-hour urine output, PLT, fever, cyanosis, dyspneic, clammy skin, piebald on the 5th day. (2) ROC curve analysis showed that the area under the ROC curve (AUC) of RF model predicting 28-day mortality was higher than that of SOFA and APACHE II score on the 1st, 3rd, 5th day (AUC: 0.836 vs. 0.643, 0.554, 0.766 and 0.590, 0.670, 0.758). The sensitivity of RF model to predict the 28-day mortality was 86.1%, the specificity was 77.0%, the accuracy was 80.7%. CONCLUSIONS: The evaluation model based on random forest can effectively predict the death risk of 28-day in patients with severe sepsis/septic shock, and its predictive efficiency is better than that of the SOFA and APACHE II score.