A Retrospective, Nested Case-Control Study to Develop a Biomarker-Based Model for ARDS Diagnostics.

BACKGROUND: Several biomarkers could be intercalated with traditional measures to improve ARDS diagnostics. METHODS: There were 211 ICU patients enrolled in this retrospective, nested case-control study. Participants were divided into an ARDS (n = 79) and non-ARDS (n = 132) groups, according to the Berlin criteria. Patient characteristics, vital signs, and laboratory tests were collected within three hours of admission. CC16, Ang-2, sRAGE, HMGB1, and SPD were measured within three hours and again at 24 hours, after admission to ICU. Receiver Operating Characteristic curves and multivariate logistic regression analyses were applied for predictive purposes. RESULTS: C-reactive protein (CRP), NT-proBNP, and pH values were intercalated with five established ARDS indicators, and the PaO2/FiO2 ratio. Only four potential indicators were analyzed, with CRP having high diagnostic value. Areas under curve (AUC) were as follows: CC16 (AUC: 0.752; 95% CI 0.680 - 0.824), Ang-2 (AUC: 0.695; 95% CI 0.620 - 0.770), HMGB1 (AUC: 0.668; 95% CI 0.592 - 0.744), sRAGE (AUC: 0.665; 95% CI 0.588 - 0.743), CRP (AUC: 0.701; 95% CI 0.627 - 0.776). No single indicator improved upon the PaO2/FiO2 ratio which had an AUC: 0.844 (95% CI 0.789 - 0.898). However, when the binary logistic model was transformed and the model was constructed, the AUC increased from 0.647 (95% CI 0.568 - 0.726) to 0.911 (95% CI 0.864 - 0.946). Among the combinations tested, PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1 resulted in the highest AUC of 0.910 (95% CI 0.863 - 0.945), although there are other factors which must be considered. CONCLUSIONS: A combination of biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we tentatively recommend PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1. This is because of the cost implications in contrast with benefit involved in utilizing the more elaborate model. Further health economics research is required to consider the opportunity cost for emergency care policy.

Renal dysfunction reduces the diagnostic and prognostic value of serum CC16 for acute respiratory distress syndrome in intensive care patients.

BACKGROUND: Contradictory results regarding changes in serum club cell protein 16 (CC16) levels in patients with acute respiratory distress syndrome (ARDS) have been reported, challenging the value of CC16 as a diagnostic and prognostic marker for ARDS. We have also observed increased serum CC16 levels in patients with renal dysfunction (RD). Therefore, the present study aimed to determine whether RD affects the diagnostic performance of CC16 for ARDS in intensive care unit (ICU) patients. METHODS: We measured serum CC16 concentrations in 479 ICU patients, who were categorized into six groups according to their diagnoses: control, acute kidney injury (AKI), chronic kidney disease (CKD), ARDS, ARDS+AKI, and ARDS+CKD. The sensitivity, specificity, and cutoff values for serum CC16 were assessed by receiver operating characteristic curve analysis. RESULTS: Serum CC16 concentrations were higher in the ARDS group than in the control group, and in ARDS patients with normal renal function, serum CC16 could identify ARDS and predict survival outcomes at 7 and 28 days. However, serum CC16 levels were similar among the ARDS+AKI, ARDS+CKD, AIK, and CKD groups. Consequently, in patients with AKI and/or CKD, the specificity of CC16 for diagnosing ARDS or ARDS+RD decreased from 86.62 to 2.82% or 81.70 to 2.12%, respectively. Consistently, the CC16 cutoff value of 11.57 ng/ml in patients with RD differed from the established values of 32.77-33.72 ng/ml with normal renal function. Moreover, the predictive value of CC16 for mortality in ARDS+RD patients was lost before 7 days but regained by 28 days. CONCLUSION: RD reduces the diagnostic specificity, diagnostic cutoff value, and predictive value for 7-day mortality of serum CC16 for ARDS among ICU patients.

Optimising the ECMO treatment regimen increases the survival rate for adult patients with acute fulminant myocarditis: A single-centre retrospective cohort study.

Background: Applying Extracorporeal membrane oxygenation (ECMO) to patients with acute fulminant myocarditis (AFM) reduces their mortality. The survival rate is 55.6-71.9% for adult AFM patients, which is lower than that for paediatric patients (63-81%). In our centre, the survival rate of ECMO for adult patients with AFM was 66.7% from January 2003 to 2012. In January 2013, the therapeutic regimen was optimised, and then the survival rate increased to 89.1% by January 2022. This article analyses the reasons for the improved survival rate following the optimisation of treatment protocols. Methods: The data for adult patients with AFM who underwent ECMO for a poor response conventional treatment from January 2003 to January 2022 were reviewed. According to different treatment regimens, the AFM patients were divided into an old and a new regimen group. Univariate and multivariate logistic regression analyses were performed on the data before and after ECMO. Results: Fifty-five patients were enrolled in the age (31.2 ± 11.3), including 24 males. Forty-nine patients were weaned successfully from ECMO [duration: (4.1 ± 1.8) d], all of whom were discharged from the hospital, with a survival rate of 89.1%. Compared with the old regimen group, the new regimen group had a shorter duration of shock to ECMO, a lower proportion of patients receiving extracorporeal cardiopulmonary resuscitation (ECPR), a lower Vasoactive Inotropic Score (VIS), and lower levels of lactic acid, and high-sensitivity troponin T before ECMO (p < 0.05). Compared with the old regimen group, after ECMO, the new regimen group had lower ECMO flow, lower proportion of left ventricular dilation and lower limb ischemia injury, the duration of ECMO was shorter, and significantly improved the survival rate, the difference was statistically significant (P < 0.05). The duration of shock to ECMO and VIS before ECMO were independent risk factors for the survival rate (p < 0.05). Conclusion: Early ECMO initiation in adult AFM patients with a poor response to conventional therapy and low-flow ECMO to meet metabolic needs can reduce serious complications affecting the prognosis, may be associated with better outcomes.

RIPK1 is a key factor in black carbon-induced cell death.

Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.

[Research progress of sepsis-induced acute kidney injury].

OBJECTIVE: Acute kidney injury (AKI) is a common complication in patients with sepsis, with poor prognosis and high mortality. The pathogenesis of sepsis-induced acute kidney injury (SAKI) is closely related to renal hemodynamic abnormalities, inflammatory injury and adaptive mechanism. It is insufficient for previous criteria based on urine output and creatinine to the early diagnosis of SAKI. The emergence of new biomarkers may make up for deficiencies in early diagnosis. And significant progress has also been made in the treatment of SAKI. The aim of this article was to review the researches on pathophysiology, early diagnosis and treatment of SAKI and provides some help for clinical staff to understand SAKI.