TM9SF1 offers utility as an efficient predictor of clinical severity and mortality among acute respiratory distress syndrome patients.

Introduction: Acute respiratory distress syndrome (ARDS) is a major cause of death among critically ill patients in intensive care settings, underscoring the need to identify biomarkers capable of predicting ARDS patient clinical status and prognosis at an early time point. This study specifically sought to explore the utility and clinical relevance of TM9SF1 as a biomarker for the early prediction of disease severity and prognostic outcomes in patients with ARDS. Methods: This study enrolled 123 patients with severe ARDS and 116 patients with non-severe ARDS for whom follow-up information was available. The mRNA levels of TM9SF1 and cytokines in peripheral blood mononuclear cells from these patients were evaluated by qPCR. The predictive performance of TM9SF1 and other clinical indicators was evaluated using received operating characteristic (ROC) curves. A predictive nomogram was developed based on TM9SF1 expression and evaluated for its ability in the early prediction of severe disease and mortality in patients with ARDS. Results: TM9SF1 mRNA expression was found to be significantly increased in patients with severe ARDS relative to those with non-severe disease or healthy controls. ARDS severity increased in correspondence with the level of TM9SF1 expression (odds ratio [OR] = 2.43, 95% confidence interval [CI] = 2.15-3.72, P = 0.005), and high TM9SF1 levels were associated with a greater risk of mortality (hazard ratio [HR] = 2.27, 95% CI = 2.20-4.39, P = 0.001). ROC curves demonstrated that relative to other clinical indicators, TM9SF1 offered superior performance in the prediction of ARDS severity and mortality. A novel nomogram incorporating TM9SF1 expression together with age, D-dimer levels, and C-reactive protein (CRP) levels was developed and was used to predict ARDS severity (AUC = 0.887, 95% CI = 0.715-0.943). A separate model incorporating TM9SF1 expression, age, neutrophil-lymphocyte ratio (NLR), and D-dimer levels (C-index = 0.890, 95% CI = 0.627-0.957) was also developed for predicting mortality. Conclusion: Increases in ARDS severity and patient mortality were observed with rising levels of TM9SF1 expression. TM9SF1 may thus offer utility as a novel biomarker for the early prediction of ARDS patient disease status and clinical outcomes.

PDCD5 as a Potential Biomarker for Improved Prediction of the Incidence and Remission for Patients with Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) often involves an altered T-cell subpopulation, higher levels of inflammatory cytokines, and auto-antibodies. This study investigated whether PDCD5 could be a biomarker to predict the incidence and remission of RA so as to guide the therapeutic management of clinical RA. METHODS: One hundred fifty-two patients (41 being in both active status and stable remission status) who were newly diagnosed with RA and 38 healthy controls were enrolled. Basic clinical data were collected before using blood samples remaining in the clinic after routine complete blood count. The ability of PDCD5 and important indicators to predict the remission of RA was estimated based on receiver operating characteristic curve (ROC) analysis. RESULTS: PDCD5 expression was found to be significantly increased in RA patients in active status in comparison with healthy controls or those in stable remission status. Compared with anti-CCP, ESR and DAS28 score, PDCD5 was of better predictive value with an AUC of 0.846 (95% CI 0.780-0.912) for RA remission. The incidence risk of RA increased with higher levels of PDCD5 (OR = 1.73, 95% CI = 1.45-1.98, P = 0.005) in multiple logistic regression analysis, with the risk increasing by 2.94-times for high-risk group in comparison with low-risk group (OR = 2.94, 95% CI = 2.35-4.62, P < 0.001). The association between PDCD5 and RA remission showed a similar result. For correlation analysis, significant associations were eventually found between PDCD5 and indicated genes (FOXP3, TNF-α, IL-17A, IFN-γ and IL-6) as well as several important clinical parameters including IgG, RF, CRP, ESR, anti-CCP and DAS28 score. CONCLUSIONS: This study suggested that increased PDCD5 expression was significantly linked to the incidence and remission of RA. PDCD5 may be used as a novel biomarker for the prediction of RA incidence and remission, especially due to its potential involvement in the development of the condition.

INCREASE IN CHLORIDE IS ASSOCIATED WITH MAJOR ADVERSE KIDNEY EVENTS IN CRITICALLY ILL PATIENTS.

ABSTRACT: Purpose: This study aimed to identify the association between hyperchloremia at intensive care unit (ICU) admission and/or the increase of blood chloride levels and the incidence of major adverse kidney events within 30 days (MAKE30) in critically ill adults. Methods: We conducted a retrospective study to analyze the data of all adult patients admitted to the ICU of a tertiary academic hospital in China between April 2020 and April 2022. Patients were categorized based on their admission chloride levels (hyperchloremia ≥110 mmol/L and nonhyperchloremia <110 mmol/L) and stratified on the increased chloride levels 48 h after ICU admission (∆Cl ≥5 mmol/L and ∆Cl <5 mmol/L). The primary outcome was the MAKE30 incidence, including in-hospital death, new receipt of renal replacement therapy (RRT), and persistent renal dysfunction (PRD). Association between hyperchloremia at ICU admission and/or the increase of chloride and the incidence of MAKE30 were assessed using logistic regression. Result: A total of 2,024 patients with a median age of 67 years (interquartile range [IQR], 55-76 years) and a median Acute Physiology and Chronic Health Evaluation II score of 22 (IQR, 17-28) were included. Hyperchloremia occurred in 30.9% (n = 625), and ΔCl ≥5 mmol/L occurred in 18.5% (n = 375) of all ICU patients. The overall MAKE30 incidence was 33.6% (n = 680), including a 10.9% of 30-day hospital mortality (n = 220; as well as overall in-hospital mortality, 11.8% [n = 238]), a 20.2% (n = 408) of PRD, and a 18.0% (n = 365) of new RRT. After adjusted for confounders, it was found that ΔCl ≥5 mmol/L (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.096-1.93; P = 0.010), but not hyperchloremia (OR, 0.99; 95% CI, 0.77-1.28; P = 0.947), was associated with increased incidence of MAKE30. Conclusion: An increased chloride level in the first 48 h of ICU admission was an independent risk factor for MAKE30, whereas hyperchloremia at ICU admission was not associated with an increased incidence of MAKE30. Large-scale prospective studies are needed to verify our findings.

Multifactorial Shock: A Neglected Situation in Polytrauma Patients.

Background: Shock after traumatic injury is likely to be hypovolemic, but different types of shock (distributive shock, obstructive shock, or cardiogenic shock) can occur in combination, known as multifactorial shock. Multifactorial shock is a neglected area of study, and is only reported sporadically. Little is known about the incidence, characteristics, and outcomes of multifactorial shock after polytrauma. Methods: A retrospective, observational, multicenter study was conducted in four Level I trauma centers involving 1051 polytrauma patients from June 2020 to April 2022. Results: The mean Injury Severity Score (ISS) was 31.1, indicating a severely injured population. The most common type of shock in the early phase after polytrauma (≤48 h) is hypovolemic shock (83.2%), followed by distributive shock (14.4%), obstructive shock (8.7%), and cardiogenic shock (3.8%). In the middle phase after polytrauma (>48 h or ≤14 days), the most common type of shock is distributive shock (70.7%), followed by hypovolemic shock (27.2%), obstructive shock (9.9%), and cardiogenic shock (7.2%). Multifactorial shock accounted for 9.7% of the entire shock population in the early phase and 15.2% in the middle phase. In total, seven combinations of multifactorial shock were described. Patients with multifactorial shock have a significantly higher complication rate and mortality than those with single-factor shock. Conclusions: This study characterizes the incidence of various types of shock in different phases after polytrauma and emphasizes that different types of shock can occur simultaneously or sequentially in polytrauma patients. Multifactorial shock has a relatively high incidence and mortality in polytrauma patients, and trauma specialists should be alert to the possibility of their occurrence.

Risk Factors for Invasive Aspergillosis in Patients Admitted to the Intensive Care Unit With Coronavirus Disease 2019: A Multicenter Retrospective Study.

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality. Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed. Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0-42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16-3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80-7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02-2.79, p = 1.02-2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA. Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.

Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China.

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

Associations of human leukocyte antigen and interleukin-18 gene polymorphisms with viral load in patients with hepatitis B infection.

This study aimed to assess the associations of human leukocyte antigen (HLA)-DR and interleukin (IL)-18 gene polymorphisms with hepatitis B virus (HBV).Clinical data were retrospectively reviewed between December 2006 and December 2015 at Xiangyang Central Hospital. HBV patients were assigned to the high and low viral load groups, respectively, according to HBV copies. HLA-DRB1*03 polymorphisms and IL-18 polymorphisms were detected by sequence-specific primer-polymerase chain reaction (PCR-SSP) and PCR-ligase detection reaction (PCR-LDR), respectively. T cell subgroups were identified by flow cytometry, and IL-18, IL-12, interferon-γ (IFN-γ), IL-4, and IL-10 expression levels were assessed by ELISA. A total of 630 subjects were included in the analysis.Compared with healthy controls, the chronic HBV group showed significantly lower IL-18 (P < .001), IL-12 (P < .001), and IFN-γ (P < .001) expression levels, and markedly increased IL-4 (P < .001) and IL-10 (P < .001) amounts. Th2 cytokine expression was high in HLA-DRB1*03 positive (+) HBV patients, with low Th1 cytokine levels. The ratios of CD4+/CD8+ and Th1/Th2 cells decreased with increasing HBV DNA levels. The chronic HBV group showed a relatively high frequency of -137G in the IL-18 gene, while IL-18 expression was low in homozygous GG genotype individuals.Polymorphisms in the HLA-DRB1*03 and IL-18 genes are associated with viral load in HBV. HLA-DRB1 and IL-18 gene polymorphisms are involved in the regulation of the Th1/Th2 balance and expression of relevant cytokines that influence immune responses in HBV.

NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide.

Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1ß, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1ß in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1ß, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice.

High levels of HB-EGF and interleukin-18 are associated with a high risk of in-stent restenosis.

OBJECTIVE: To explore the clinical significance of heparin-binding epidermal growth factor-like growth factor (HB-EGF), interleukin-18 (IL-18), and interleukin-10 (IL-10) in restenosis after percutaneous coronary intervention (PCI). METHODS: A total of 198 patients with acute coronary syndrome underwent coronary drug-eluting stent implantation and were divided into the restenosis group and non-restenosis group on the basis of second coronary angiography. Biological parameters and HB-EGF, IL-18, and IL-10 levels were measured. Patients in the restenosis group were further divided into 3 subgroups according to Gensini score: group A (Gensini score of <20), group B (Gensini score of ≥20 but <40), and group C (Gensini score of ≥40). RESULTS: Compared with the non-restenosis group, HB-EGF and IL-18 levels were significantly higher but serum IL-10 levels were significantly lower in the restenosis group. Furthermore, HB-EGF levels increased with the Gensini score among the 3 subgroups. Spearman's correlation analysis showed that HB-EGF levels were associated with IL-18 levels and the number of diseased vessels. Multivariate logistic regression analysis showed that diabetes, HB-EGF, and IL-18 were risk factors for restenosis [odds ratio with 95% confidence interval: 3.902 (1.188-4.415), 2.185 (1.103-4.014), and 2.079 (1.208-4.027), respectively]. CONCLUSION: The present study has demonstrated that HB-EGF may be used to evaluate the severity of restenosis and coronary artery lesion and that inflammatory responses may be involved in the process of restenosis.