The role of proadrenomedullin, interleukin 6 and CD64 in the diagnosis and prognosis of septic shock.

INTRODUCTION: Sepsis and septic shock are disorders of tissue perfusion and microcirculation associated with increased mortality. The role of biomarkers such as proadrenomedullin (PRO-ADM), interleukin 6 (IL-6) and neutrophil CD64 (CD64) in the diagnosis and prognosis of septic shock has been studied. METHODS: GCS, SOFA score, APACHE 2 score, lactate, CRP, procalcitonin, PRO-ADM, IL-6, CD64 level and 28-day mortality were evaluated in patients with septic shock followed-up in the intensive care unit of Marmara University Hospital between July 2021 and December 2021. The study was planned as prospective, non-drug clinical research Committee. RESULTS: There were no statistically significant differences between patient groups in gender, BMI, and presence of comorbidities (p > 0.05). The alive patient group had significantly higher GCS values and lower SOFA, APACHE 2, lactate and CD64 values than the dead patient group (p < 0.01). The cut-off values of laboratory parameters were determined using ROC analysis to predict mortality, SOFA and CD64 had high AUC. This is also a good indicator for mortality.The multivariate logistic regression model was estimated using the backward selection method. The mortality of ICU patients was predicted by a SOFA-value ≥ 12 (OR (95%CI) = 56.13 (5.44-578.64)), CD64 value ≥ 28.54 (OR (95% CI) = 23.78 (2.61-216.85)), and ADM-value ≥ 86.79 (OR (95% CI) = 15.86 (1.02-246.49)) (p < 0.05) . CONCLUSION: In conclusion, serum CD64 level, PRO-ADM level, and SOFA score proved to be effective parameters for predicting prognosis and mortality in septic shock. However, IL-6 proved to be a weak biomarker and failed to predict mortality. CD64, which is easier and more practical to use, can be used instead of the SOFA score.

Identification of Inflammation-Related Biomarker Pro-ADM for Male Patients With Gout by Comprehensive Analysis.

Objective: Gout is a local inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints or adjacent tissues. When some gout occurs without hyperuricemia, or its clinical symptoms and signs are not typical, the diagnosis of gout will be delayed, so there is an urgent need to find a new biomarker to predict and diagnose of gout flare. Our research attempts to find the key genes and potential molecular mechanisms of gout through bioinformatics analysis, and collected general data and blood biochemical samples of patients with gout and healthy, then analyzed and compared the expression of factors regulated by key genes. Method: GSE160170 were downloaded from GEO database for analysis. The data were normalized to identify the differentially expressed genes (DEGs), then GO and KEGG enrichment analysis were applied. Protein-protein interaction (PPI) networks and hub genes between DEGs were identified. Then collect general information and blood samples from male patients with acute gout, hyperuricemia and healthy. ELISA method was used to detect pro-ADM levels of different groups, and the data was input into SPSS statistical software for analysis. Result: We identified 266 DEGs (179 up-regulated and 87 down-regulated) between gout patients and healthy controls. GO analysis results show that DEGs are mostly enriched in inflammatory response, growth factor activity, cytokine activity, chemokine activity, S100 protein binding and CXCR chemokine receptor binding. KEGG pathway analysis showed that DEGs are mainly related to Chemokine signaling pathway and Cytokine-cytokine receptor interaction. ADM, CXCR1, CXCR6, CXCL3, CCL3, CCL18, CCL3L3, CCL4L1, CD69, CD83, AREG, EREG, B7RP1, HBEGF, NAMPT and S100B are the most important hub genes in the PPI network. We found that the expression of pro-ADM in the gout group and hyperuricemia group was higher than that in the healthy group, and the difference was statistically significant. Conclusion: In this study, a series of bioinformatics analyses were performed on DEGs to identify key genes and pathways related to gout. Through clinical verification, we found that pro-ADM can be used as an inflammation-related biomarker for acute attacks of gout, providing new ideas for the diagnosis and treatment of gout.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study.

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for mortality were 2.40 and 0.46, respectively. The LR+ and LR- for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62-0.81) and 0.72 (95% CI, 0.62-0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

Assessment of novel biomarkers: sTREM-1, pentraxin-3 and pro-adrenomedullin in the early diagnosis of neonatal early onset sepsis.

BACKGROUND: Early onset bacterial sepsis in neonates (EOS) is recognized as an important health condition. Early diagnosis is crucial. However, blood culture results are released in 48-72 hours. Many biomarkers have been investigated but none have been accepted as the gold standard. This study aimed to investigate the diagnostic value of the molecules: soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1), pentraxin-3 (PTX-3) and pro adrenomedullin (pro-ADM) in EOS and compare with currently used biomarkers. METHODS: In this multicenter prospective study, patients were enrolled from different NICUs around the Turkey. Patient data were collected via web-based registry system from attending centers. Neonates, hospitalized with a suspicion of EOS were enrolled. Blood culture and routine blood tests were collected and a serum sample was obtained and kept in - 80°C for studying the molecules. According to laboratory results, patients were divided into three groups as; proven sepsis, clinical sepsis and control group. Groups were compared in terms of demographic, clinical and laboratory findings. The primary outcome of the study was to assess any difference between groups in terms of the diagnostic value of the markers aforementioned. RESULTS: A total of 130 patients were enrolled; proven sepsis (n = 36), clinical sepsis (n = 53) and control (n = 41) groups. Groups were similar in terms of demographic findings; mean WBC (P = 0.445), procalcitonin (PCT) (P = 0.083) and IL-6 (P = 0.814) levels. Mean C-reactive protein (CRP) level was significantly higher in clinical sepsis and proven sepsis groups compared to control group (P < 0.001). Mean PTX-3 (P = 0.547), pro-ADM (P = 0.766) and sTREM-1 (P = 0.838) levels were similar between groups. CONCLUSION: These promising molecules failed to help in early diagnosis of EOS. Their relation to correlation with disease progression may make more sense as they seem to be expressed in higher amounts with the progression of the disease in previous studies. CRP was the most frequently used biomarker for detecting the sepsis in our study population.

The role of immune and metabolic biomarkers for improved management of sepsis patients.

Sepsis, the body`s overwhelming response to systemic infections, is responsible for significant morbidity, mortality, and financial burden. Pathogens and their antigens stimulate pro- and anti-inflammatory mediators and immune markers which characterize the host defense and orchestrate leukocyte recruitment to the acute site of infection. Different immune and metabolic biomarkers have been studied in relation to sepsis for their diagnostic and/or prognostic aid. Recent studies have provided abundant evidence that specific immune and metabolic biomarkers improve a physician`s ability to guide early sepsis recognition, severity assessment and therapeutic decisions in individual patients. This may allow for a transition from bundled sepsis care (protocols combining several medical practices) to more individualized management. First, lactate has now been widely used for risk stratification and guidance of fluid resuscitation. Second, procalcitonin correlates with risks of bacterial infections and helps guide therapeutic decisions about initiation and withdrawal of anti-microbial therapy. Third, prognostic markers such as pro-adrenomedullin improve early mortality prediction and thereby site-of-care decisions in respiratory infections. For these markers interventional trials have documented their value when integrated in clinical protocols.

ICG-liver test versus new biomarkers as prognostic markers for prolonged length of stay in critically ill patients - a prospective study of accuracy for prediction of length of stay in the ICU.

BACKGROUND: Prognostic abilities of medical parameters, which are scoring systems, measurements and biomarkers, are important for stratifying critically ill patients. Indocyanine green plasma disappearance (ICG-PDR) is an established clinical tool for the assessment of liver perfusion and function. Copeptin, MR-proANP and pro-ADM are biomarkers whose prognostic value is still unclear. The goal of this prospective study was to evaluate ICG-PDR, copeptin, MR-proANP and pro-ADM to predict prolonged length of stay (pLOS) in the ICU. METHODS: This study was conducted as a prospective single center study including 110 consecutively admitted ICU patients. Primary endpoint was prolonged length of stay (pLOS) in the ICU, defined as more than three days of stay there. RESULTS: ROC analysis showed an AUC of 0.73 for ICG-PDR, 0.70 for SAPS II, 0.65 for MR-proANP, 0.64 for pro-ADM and 0.54 for copeptin for pLOS in the ICU. CONCLUSIONS: The prediction of pLOS in the ICU might be better by means of ICG-PDR than with the new biomarkers copeptin, MR-proANP or pro-ADM. Nevertheless, there is more need for research to evaluate whether ICG-PDR is an overall prognostic marker for pLOS. TRIAL REGISTRATION: (ClinicalTrials.gov number, NCT01126554).