Plasma proenkephalin and neutrophil gelatinase-associated lipocalin predict mortality in ICU patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients admitted to intensive care unit (ICU) and mortality rates for this condition are high. To reduce the high incidence of short-term mortality, reliable prognostic indicators are required to facilitate early diagnosis and treatment of AKI. We assessed the ability of plasma proenkephalin (p­PENK) and plasma neutrophil gelatinase-associated lipocalin (p­NGAL) to predict 28-day mortality in AKI patients in intensive care. METHODS: This prospective study, carried out between January 2019 and December 2019, comprised 150 patients (100 male) diagnosed with AKI after excluding 20 patients discharged within 24 h and those with missing hospitalization data. Blood samples were collected to determine admission p-PENK and p-NGAL levels. The study outcome was 28­day mortality. RESULTS: The mean patient age was 68 years (female, 33%). The average P­PENK and p­NGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. P­PENK levels >0.36 ng/µL and p­NGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28­day mortality for patients with AKI (adjusted hazard ratios 0.785 [95% confidence interval 0.706-0.865, P<0.001] and 0.700 [95% confidence interval 0.611-0.789, P<0.001], respectively). This association was significant for mortality in patients in intensive care with AKI. Baseline p-PENK (0.36 ng/µL) and p-NGAL (230.30 ng/mL) levels and their respective cut-off values showed clinical value in predicting 28-day mortality. CONCLUSION: Serum PENK and NGAL levels, when used in conjunction, improved the accuracy of predicting 28-day mortality in patients with AKI while retaining sensitivity and specificity.

Health Care-Associated Infection in Elderly Patients With Cerebrovascular Disease in Intensive Care Units: A Retrospective Cohort Study in Taizhou, China.

BACKGROUND: Cerebrovascular diseases are associated with high incidence of health care-associated infections (HAIs) and poor prognosis in elderly patients. This study aimed to investigate the incidence and clinical characteristics of HAIs in elderly patients with cerebrovascular disease in the intensive care unit (ICU). METHODS: Patients admitted with cerebrovascular disease, aged ≥65 years, were included. The clinical data of the patients were retrospectively analyzed to determine the risk factors, infection type, distribution, and pathogenic characteristics of HAIs in the context of cerebrovascular diseases. RESULTS: Out of 381 ICU inpatients monitored, 79 (20.73%) developed HAIs. Risk analysis revealed number of ventilator days as significant risk factors for HAIs in elderly patients with cerebrovascular diseases in the comprehensive ICU. In the HAI group, 56 patients (70.89%) had respiratory tract infection (RTI). Sixty-five patients (82.28%) were infected with Gram-negative bacteria (GNB), and 42 (53.16%) with multi-drug-resistant organism (MDRO). The length of hospitalization days, ventilator days, and overall hospitalization costs were higher in the HAI group than in the non-HAI group (P < 0.05), but there was no significant difference between groups in the treatment outcome of patients. Patients with MDRO infection had longer duration and higher cost of hospitalization than those infected with non-MDRO (P < 0.05), but there was no significant difference between the groups in the treatment outcome of patients. CONCLUSIONS: HAIs occurred mostly due to RTI and GNB infection. The hospitalization cost and duration, as well as the length of ventilator days, were higher for cerebrovascular patients with HAIs than for non-HAIs patients.

Incidence and clinical features of HHV-7 detection in lower respiratory tract in patients with severe pneumonia: a multicenter, retrospective study.

PURPOSE: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. METHODS: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. RESULTS: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein-Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936-3.400, p = 0.079). CONCLUSION: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein-Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.

Nur77 Serves as a Potential Prognostic Biomarker That Correlates with Immune Infiltration and May Act as a Good Target for Prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the most frequent malignancy, and is the second leading cause of death due to cancer in men. Thus, new prognostic biomarkers and drug targets for PRAD are urgently needed. As we know, nuclear receptor Nur77 is important in cancer development and changes in the tumor microenvironment; whereas, the function of Nur77 in PRAD remains to be elucidated. The TCGA database was used to explore the Nur77 expression and its role in the prognosis of PRAD. It was shown that Nur77 was down regulated in PRAD, and low Nur77 expression was correlated with advanced clinical pathologic characteristics (high grade, histological type, age) and poor prognosis. Furthermore, key genes screening was examined by univariate Cox analysis and Kaplan-Meier survival. Additionally, Nur77 was closely related to immune infiltration and some anti-tumor immune functions. The differentially expressed genes (DEGs) were presented by protein-protein interaction (PPI) network analysis. Therefore, the expression level of Nur77 might help predict the survival of PRAD cases, which presents a new insight and a new target for the treatment of PRAD. In vitro experiments verified that natural product malayoside targeting Nur77 exhibited significant therapeutic effects on PRAD and largely induced cell apoptosis by up-regulating the expression of Nur77 and its mitochondrial localization. Taken together, Nur77 is a prognostic biomarker for patients with PRAD, which may refresh the profound understanding of PRAD individualized treatment.

Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis.

BACKGROUND: Sepsis is defined as a systemic inflammatory response to microbial infections with multiple organ dysfunction. This study analysed untargeted metabolomics combined with proteomics of serum from patients with sepsis to reveal the underlying pathological mechanisms involved in sepsis. METHODS: A total of 63 patients with sepsis and 43 normal controls were enrolled from a prospective multicentre cohort. The biological functions of the metabolome were assessed by coexpression network analysis. A molecular network based on metabolomics and proteomics data was constructed to investigate the key molecules. RESULTS: Untargeted metabolomics analysis revealed widespread dysregulation of amino acid metabolism, which regulates inflammation and immunity, in patients with sepsis. Seventy-three differentially expressed metabolites (|log2 fold change| > 1.5, adjusted P value < 0.05 and variable importance in the projection (VIP) > 1.5) that could predict sepsis were identified. External validation of the hub metabolites was consistent with the derivation results (area under the receiver operating characteristic curve (AUROC): 0.81-0.96/0.62-1.00). The pentose phosphate pathway was found to be related to sepsis-associated encephalopathy. Phenylalanine metabolism was associated with sepsis-associated acute kidney injury. The key molecular alterations of the multiomics network in sepsis compared to normal controls implicate acute inflammatory response, platelet degranulation, myeloid cell activation involved in immune response and phenylalanine, tyrosine and tryptophan biosynthesis, and arginine biosynthesis. CONCLUSIONS: Integrated analysis of untargeted metabolomics and proteomics revealed characteristic metabolite and protein alterations in sepsis, which were mainly involved in inflammation-related pathways and amino acid metabolism. This study depicted the pathological characteristics and pathways involved in sepsis and potential therapeutic targets.

Toxicity evaluation, toxin screening and its intervention of the jellyfish Phacellophora camtschatica based on a combined transcriptome-proteome analysis.

BACKGROUND: The application of multi-omics technologies provides a new perspective to solve three main problems including species identification, toxin screening and effective antagonist conformation in the studies of marine toxic jellyfish. METHODS: A series of transcriptome-proteome based analysis accompanied with toxicity evaluations were performed for the ornamental jellyfish Phacellophora camtschatica. RESULTS: Through combined morphological observation and Cytochrome c oxidase subunit Ⅰ (CO1) molecular alignment, the sample jellyfish was identified as P. camtschatica. A total of 25,747 unigenes and 3058 proteins were obtained from the successfully constructed transcriptome and proteome, in which 6869 (26.68%) and 6618 (25.70%) unigenes, as well as 2536 (82.93%) and 2844 (93.00%) proteins were annotated against the databases of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), respectively. The jellyfish displayed obvious in vivo lethal effects with significant increases of multi-organ functional indexes as well as in vitro activities. Total of 62 toxins from 120 toxin-related unigenes were screened including 16 metalloproteases, 11 phospholipases and others. Moreover, 11 toxins were further screened by using the erythrocyte model, where the zinc metalloproteinase nas-15-like (1) was the most abundant. Finally, Diltiazem greatly improved the survival rate while EDTA slightly prolonged the survival time in ICR mice. CONCLUSION: P. camtschatica is a poisonous jellyfish with diversified toxic components, in which metalloproteinase probably plays an important role in toxicities, and excessive Ca2+ entry may be the main mechanism of systemic lethal toxicity.

Serum proteomics reveals disorder of lipoprotein metabolism in sepsis.

Sepsis is defined as an organ dysfunction syndrome and it has high mortality worldwide. This study analysed the proteome of serum from patients with sepsis to characterize the pathological mechanism and pathways involved in sepsis. A total of 59 patients with sepsis were enrolled for quantitative proteomic analysis. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network specific to sepsis. Key regulatory modules that were detected were highly correlated with sepsis patients and related to multiple functional groups, including plasma lipoprotein particle remodeling, inflammatory response, and wound healing. Complement activation was significantly associated with sepsis-associated encephalopathy. Triglyceride/cholesterol homeostasis was found to be related to sepsis-associated acute kidney injury. Twelve hub proteins were identified, which might be predictive biomarkers of sepsis. External validation of the hub proteins showed their significantly differential expression in sepsis patients. This study identified that plasma lipoprotein processes played a crucial role in sepsis patients, that complement activation contributed to sepsis-associated encephalopathy, and that triglyceride/cholesterol homeostasis was associated with sepsis-associated acute kidney injury.

The spatiotemporal trend of renal involvement in COVID-19: A pooled analysis of 17 134 patients.

BACKGROUND: The spatiotemporal trend of renal involvement in coronavirus disease 2019 (COVID-19) patients is still unclear. Therefore, the aim of this study was to reveal the dynamics of renal involvement superimposed COVID-19 according to time and space. METHODS: COVID-19 patients reporting renal involvement were included in this study. The following information was collected from relevant articles: first author, patient demographics, patient enrollment period, location, definition of acute kidney injury (AKI), prevalence of AKI, and use of renal replacement therapy (RRT). RESULTS: A total of 17 134 patients were finally included. The overall prevalence of AKI in COVID-19 patients was 19%, with 7% of them undergoing RRT. The overall risk of AKI in patients enrolled before March 1, 2020 (9%) was significantly lower than that after March 1, 2020 (36%) (P < 0.00001). Moreover, the overall risk of AKI outside Asia (35%) was significantly higher than that in Asia (10%) (P < 0.00001). Additionally, similar to patients requiring RRT, AKI patients were more likely to become seriously ill or even to die (P < 0.00001). CONCLUSIONS: This study found that renal involvement superimposed COVID-19, a comorbidity portending a poor prognosis, has become an increasingly serious problem over time and is more common outside Asia. Thus, more attention should be paid to the management of this specific group of patients.

Comprehensive Transcriptome Profiling of Peripheral Blood Mononuclear Cells from Patients with Sepsis.

Background: Sepsis, as a clinical emergency, usually causes multiorgan dysfunction and can lead to high mortality. Establishment of specific and sensitive biomarkers for early diagnosis is critical to identify patients who would benefit from targeted therapy. In this study, we investigated this syndrome by analyzing the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with sepsis and identified sepsis-specific biomarkers. Methods: In this study, a total of 87 patients with sepsis and 40 healthy controls from a prospective multicenter cohort were enrolled. Samples from 44 subjects (24 patients with sepsis and 20 healthy controls) were sequenced and the remaining patients were included in the validation group. Using high-throughput sequencing, a gene expression profile of PBMCs from patients with sepsis was generated to elucidate the pathophysiology of sepsis and identify sepsis-specific biomarkers. Results: Principal component analysis (PCA) and unsupervised hierarchical cluster analysis showed that patients with sepsis separated from healthy controls. A total of 1639 differentially expressed genes (DEGs) were identified (|log2 fold change|>2, adjusted P value <0.05) between these two groups, with 1278 (78.0%) upregulated and 361 (22.0%) downregulated in patients with sepsis. Gene Ontology (GO) analysis of the upregulated DEGs identified 194 GO terms that were clustered into 27 groups, and analysis of the downregulated DEGs identified 20 GO terms that were clustered into 4 groups. Four unique genes were identified that could be predictive of patients with sepsis. External validation of the four genes using quantitative real-time polymerase chain reaction (qRT-PCR) was consistent with the results of mRNA sequencing, revealing their potential in sepsis diagnosis. Conclusions: The transcriptome characteristics of PBMCs, which were significantly altered in sepsis patients, provide new insights into sepsis pathogenesis. The four identified gene expression changes differentiated patients with sepsis from healthy subjects, which could serve as a convenient tool contributing to sepsis diagnosis.

Ultra-high pre-membrane lung oxygen saturation in a patient on veno-arterial extracorporeal membrane oxygenation.

A 55-year-old man who suffered from acute myocardial infarction complicated with cardiogenic shock was administered veno-arterial extracorporeal membrane oxygenation. Ultra-high pre-membrane lung oxygen saturation of 93% was observed. Transthoracic echocardiography revealed the presence of patent foramen ovale. The four-chamber view showed that the tip of the cannula was located in the patent foramen ovale, which resulted in a left-to-right shunt. Without adjusting the position of the drainage cannula, the patient was weaned from extracorporeal membrane oxygenation at 136 hours after initiation and survived to hospital discharge.

Effectiveness of enteral feeding protocol on clinical outcomes in critically ill patients: a study protocol for before-and-after design.

INTRODUCTION: Enteral feed is an important component of nutritional therapy in critically ill patients and underfeeding has been associated with adverse outcomes. The article developed an enteral feeding protocol and planed a before-and-after comparative trial to explore whether implementation of enteral feeding protocol was able to improve clinical outcomes. METHODS AND ANALYSIS: The study will be conducted in intensive care units (ICUs) of ten tertiary care academic centers. Critically ill patients expected to stay in ICU for over 3 days and require enteral nutrition (EN) were potentially eligible. This is a before-and-after study comprising three phases: The first phase is the period without enteral feeding protocol; the second phase involves four-week training program, and the last phase is to perform the protocol in participating centers. We plan to enroll a total of 350 patients to provide an 80% power and 0.05 error rate to detect a 15% reduction of mortality. The primary outcome is 28-day mortality. ETHICS AND DISSEMINATION: Ethical approval to conduct the research has been obtained from all participating centers. Additionally, the results will be published in peer-reviewed journal. TRIAL REGISTRATION: The study was registered at International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry (ISRCTN10583582).