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The Utility of Biomarkers in Disease Management Approach

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A topical collection in Medicina (ISSN 1648-9144). This collection belongs to the section "Translational Medicine".

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Prof. Dr. Salvatore Di Somma

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Guest Editor

Emergency Medicine Department of Medical-Surgery Sciences and Translational Medicine, "University or Rome Sapienza", Rome, Italy
Interests: acute cardiovascular disease; biomarkers in critical care; sepsis; acute kidney injury

Dr. David Brenner

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Guest Editor

Department of Medicine, University of California San Diego, La Jolla, CA, USA
Interests: biomarkers in clinical practise; epigenetic; mycrobyoma; metabolomics; longevity

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Dear Colleagues,

Traditionally, in a product’s lifecycle, we consider a truth-seeking early stage focused on evaluating novel products’ prospects and eliminating bad bets, and a success-seeking late stage focused on maximizing the value of products that have been cleared for development. However, a third step which is strictly related to the first two is the understanding of the need for innovation, evaluation in the context of the healthcare system, as well as individual patients, and programs to assure that value, not just novelty, supports medical innovation.

So-called translational research has the ultimate objective of impacting longer-term outcomes with reduced healthcare utilization. One of the most important assumptions at the basis of translational research is that established medical tools can be “optimized” using genetic, biological, and phenotypic information. The scheme below illustrates the steps characterizing translational research:

The unique opportunity to use biomarkers as model for translational medicine:

Researchers navigate the ocean of biomarkers searching for proper targets and their optimal utilization. Emergency medicine builds up the frontline to maximize the utility of clinically validated biomarkers and is the cutting-edge field to test the applicability of promising biomarkers emerging from thorough translational research. The role of biomarkers in clinical decision making would be of greater significance for the identification, risk stratification, monitoring, and prognostication of patients in critical and acute care settings. There is no doubt that basic research to explore novel biomarkers in relation to pathogenesis is as important as its clinical counterpart.

The challenges being faced at the moment include:

Previously unknown biomarkers;
Known biomarkers which have either has not been determined routinely or have been determined routinely but not been used for identifying responders for medicine “X”;
Patient groups of responders which are different to the formerly treated groups;
Patient groups of responders which overlap a) substantially or b) not substantially with the formerly treated groups;
Patient groups of responders which are a) smaller or b) bigger subgroups of the formerly treated groups.

You are kindly invited to submit your manuscript on “The Utility of Biomarkers in Disease Management Approach” for a Special Issue of Medicina.

Prof. Dr. Salvatore Di Somma
Dr. David Brenner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

translational medicine
biomarkers
biomarkers in acute diseases
biomarkers in chronic disease monitoring
biomarkers and therapeutic decision making

Published Papers (12 papers)

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2023

Jump to: 2022

11 pages, 2083 KiB

Open AccessArticle

High Wnt2 Expression Confers Poor Prognosis in Colorectal Cancer, and Represents a Novel Therapeutic Target in BRAF-Mutated Colorectal Cancer

by Huan Liu, Lihua Zhang, Ye Wang, Rendi Wu, Chenjie Shen, Guifang Li, Shiqi Shi, Yong Mao and Dong Hua

Medicina 2023, 59(6), 1133; https://doi.org/10.3390/medicina59061133 - 12 Jun 2023

Viewed by 1195

Abstract

Background and Objectives: We aimed to investigate the role of Wnt2 expression in colorectal cancer (CRC) prognosis and evaluate its potential as a therapeutic target in BRAF-mutated CRC. Materials and Methods: Exactly 136 samples of formalin-fixed paraffin-embedded CRC tissue specimens were obtained from patients who underwent surgical resection for CRC. The gene mutation status of the samples was detected using fluorescence PCR. Wnt2 expression was detected using immunohistochemistry. Survival curves with high Wnt2 expression and BRAF mutations were compared using the Kaplan–Meier method. A nomogram was constructed to determine the estimated overall survival probability. We also predicted the 3-year and 5-year survival rates for patients with high Wnt2 expression and BRAF mutations. In total, 50 samples of BRAF-mutated CRC were collected and detected Wnt2 expression by immunohistochemistry. The Chi-squared test was used to analyze the association between Wnt2 expression and BRAF-mutated CRC. Results: High Wnt2 expression and BRAF mutations are associated with poor prognosis of CRC. Multivariate survival analyses indicated that high Wnt2 expression and BRAF mutations are significant independent predictors of CRC prognosis. Furthermore, high Wnt2 expression was significantly associated with BRAF-mutated CRC, and Wnt2 may be a potential therapeutic target for BRAF-mutated CRC. Conclusions: High Wnt2 expression confers poor prognosis in colorectal cancer and represents a novel therapeutic target in BRAF-mutated CRC. Full article

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10 pages, 588 KiB

Open AccessArticle

Prognostic Value for Mortality of Plasma Bioactive Adrenomedullin in Patients with Pulmonary Arterial Hypertension: A Sub Analysis of the Biomarker Study in the COHARD-PH Registry

by Anggoro Budi Hartopo, Dyah Wulan Anggrahini, Lucia Kris Dinarti, Anne-Kathrin Schäfer, Andreas Bergmann, Jajah Fachiroh and Salvatore Di Somma

Medicina 2023, 59(4), 748; https://doi.org/10.3390/medicina59040748 - 12 Apr 2023

Cited by 1 | Viewed by 1646

Abstract

The adrenomedullin level increases in pulmonary arterial hypertension (PAH, and correlates with a high mortality rate. Its active form, bioactive adrenomedullin (bio-ADM), has been recently developed and has significant prognostic applications in acute clinical settings. Aside from idiopathic/hereditary PAH (I/H-PAH), atrial septal defects-associated pulmonary artery hypertension (ASD-PAH) is still prevalent in developing countries and associated with increased mortality. This study aimed to investigate the mortality-wise prognostic value of the plasma bio-ADM level by comparing subjects with ASD-PAH and I/H-PAH with ASD patients without pulmonary hypertension (PH) as a control group. This was a retrospective, observational cohort study. The subjects were Indonesian adult patients who were recruited from the Congenital Heart Disease and Pulmonary Hypertension (COHARD-PH) registry and divided into three groups: (1) ASD without PH (control group), (2) ASD-PAH and (3) I/H-PAH. During right-heart catheterization at the time of diagnosis, a plasma sample was taken and assayed for bio-ADM using a chemiluminescence immunoassay. Follow-up was performed as a part of the COHARD-PH registry protocol in order to evaluate the mortality rate. Among the 120 subjects enrolled: 20 turned out to have ASD without PH, 85 had ASD-PAH and 15 had I/H-PAH. Compared to the control group (5.15 (3.0–7.95 pg/mL)) and ASD-PAH group (7.30 (4.10–13.50 pg/mL)), bio-ADM levels were significantly higher in the I/H-PAH group (median (interquartile range (IQR)): 15.50 (7.50–24.10 pg/mL)). Moreover, plasma bio-ADM levels were significantly higher in subjects who died (n = 21, 17.5%) compared to those who survived (median (IQR): 11.70 (7.20–16.40 pg/mL) vs. 6.90 (4.10–10.20 pg/mL), p = 0.031). There was a tendency toward higher bio-ADM levels in those who died among the PAH subjects, in both ASD-PAH and I/H-PAH groups. In conclusion, the plasma bio-ADM level is elevated in subjects with PAH from both ASD-PAH and I/H-PAH origins, reaching the highest levels in subjects with the I/H-PAH form. A high bio-ADM level tended to be associated with a high mortality rate in all subjects with PAH, indicating a relevant prognostic value for this biomarker. In patients with I/H-PAH, monitoring bio-ADM could represent a valid tool for predicting outcomes, allowing more appropriate therapeutical choices. Full article

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13 pages, 5659 KiB

Open AccessArticle

Predictive Value of Gene Databases in Discovering New Biomarkers and New Therapeutic Targets in Lung Cancer

by Mengfeng Liu, Xiran Yu, Changfa Qu and Shidong Xu

Medicina 2023, 59(3), 547; https://doi.org/10.3390/medicina59030547 - 10 Mar 2023

Cited by 1 | Viewed by 1598

Abstract

Background and Objectives: The molecular mechanisms of lung cancer are still unclear. Investigation of immune cell infiltration (ICI) and the hub gene will facilitate the identification of specific biomarkers. Materials and Methods: Key modules of ICI and immune cell-associated differential genes, as well as ICI profiles, were identified using lung cancer microarray data from the single sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) in the gene expression omnibus (GEO) database. Protein–protein interaction networks were used to identify hub genes. The receiver operating characteristic (ROC) curve was used to assess the diagnostic significance of the hub genes, and survival analysis was performed using gene expression profiling interactive analysis (GEPIA). Results: Significant changes in ICI were found in lung cancer tissues versus adjacent normal tissues. WGCNA results showed the highest correlation of yellow and blue modules with ICI. Protein–protein interaction networks identified four hub genes, namely CENPF, AURKA, PBK, and CCNB1. The lung adenocarcinoma patients in the low hub gene expression group showed higher overall survival and longer median survival than the high expression group. They were associated with a decreased risk of lung cancer in patients, indicating their potential role as cancer suppressor genes and potential targets for future therapeutic development. Conclusions: CENPF, AURKA, PBK, and CCNB1 show great potential as biomarkers and immunotherapeutic targets specific to lung cancer. Lung cancer patients’ prognoses are often foreseen using matched prognostic models, and genes CENPF, AURKA, PBK, and CCNB1 in lung cancer may serve as therapeutic targets, which require further investigations. Full article

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11 pages, 704 KiB

Open AccessArticle

Utility of Combining High-Sensitive Cardiac Troponin I and PESI Score for Risk Management in Patients with Pulmonary Embolism in the Emergency Department

by Elisa Cennamo, Gabriele Valli, Engy Khaled Mohamed Riead, Silvia Casalboni, Ilaria Dafne Papasidero, Francesca De Marco, Anna Mariani, Paola Pepe, Giuseppe Santangelo, Marina Mastracchi, Paolo Fratini, Giacinta Pistilli, Pasquale Pignatelli, Maria Pia Ruggieri and Salvatore Di Somma

Medicina 2023, 59(2), 185; https://doi.org/10.3390/medicina59020185 - 17 Jan 2023

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Abstract

Background and Objectives: Pulmonary embolism (PE) has a major burden of morbidity and mortality, consequently the need for a prompt risk stratification for these subjects is crucial. In order to evaluate the risk management and final disposition of patients with PE in the Emergency Department (ED), we conducted a study that was divided in two phases: Phase I retrospective study (RS), Phase II prospective study (PS). Materials and Methods: In Phase I, 291 patients were enrolled while in Phase II, 83 subjects were evaluated. In both study phases, the enrolled subjects were analyzed for final disposition in ED using PESI score, right ventricle (RV) imaging, and high-sensitive cardiac troponin I (hs-cTnI) data. The RS patients were divided into low risk and high risk according to the sPESI score, while PS patients were grouped in low, intermediate, and high risk classes according to PESI score. In both study phases, all the studied patients were further divided into negative (hs-cTnI−) or positive (hs-cTnI+) groups according to hs-cTnI levels within normal or above cutoff values, respectively. For all enrolled subjects, CT pulmonary angiography was analyzed to assess the RV/LV diameter and volume ratio as an indicator of RV involvement. Results: In both RS and PS phases, hs-cTnI+ group showed a higher PESI score. Nevertheless, a significant percentage of hs-cTnI+ patients resulted to be in the low-risk PESI class. Patients with a positive RV/LV ratio were more likely to have a hs-cTnI+ (p < 0.01), while among those with a negative ratio, 24 to 32% showed as hs-cTnI+. In the hs-cTnI+ group from both study phases, patients were more likely to be admitted in an ICU (RR 3.7, IC: 2.1–6.5). Conclusions: In conclusion, in patients with PE in the ED compared PESI score alone, the combination of hs-cTnI and PESI seems to be of greater utility in improving risk stratification and final disposition decision-making. Full article

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2022

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13 pages, 1389 KiB

Open AccessArticle

30 Days Mortality Prognostic Value of POCT Bio-Adrenomedullin and Proenkephalin in Patients with Sepsis in the Emergency Department

by Silvia Casalboni, Gabriele Valli, Ferdinando Terlizzi, Marina Mastracchi, Giacomo Fidelio, Francesca De Marco, Caterina Bernardi, Anastasia Chieruzzi, Alessia Curcio, Francesco De Cicco, Nicola Colella, Ilaria Dafne Papasidero, Emanuele Tartarone, Maria Pia Ruggieri and Salvatore Di Somma

Medicina 2022, 58(12), 1786; https://doi.org/10.3390/medicina58121786 - 04 Dec 2022

Cited by 5 | Viewed by 2559

Abstract

Background and Objective: Sepsis is a worldwide severe disease with a high incidence and mortality rate. Sepsis is a frequent cause of admission to the emergency department (ED). Although prognostic scores (Sequential Organ Failure Assessment, SOFA; New Early Warning Score, NEWS; Rapid Emergency Medicine Score, REMS) are commonly used for risk stratification in septic patients, many of these scores are of poor utility in the ED. In this setting, biomarkers are promising alternatives, easier to perform and potentially more specific. Bio-adrenomedullin (Bio-ADM) and Proenkephalin (PenKid) seem to have a key role in the development of organ dysfunctions induced by sepsis and, therefore, could help in the risk stratification of patients with sepsis at ED admission. The aim of this study was to evaluate the utility of Bio-ADM and PenKid, obtained through a point of care (POCT) device, in predicting 30 days mortality for patients presenting to the ED with sepsis. Methods and Results: In total, 177 consecutive adult patients with a diagnosis of sepsis presenting to the ED of San Giovanni Addolorata Hospital in Rome, Italy, between May 2021 and April 2022 were enrolled in this prospective observational study. For each patient, Bio-ADM and PenKid were obtained at ED admission together with SOFA, NEWS and REMS scores. Next, 30 days follow-up data were collected to evaluate patient mortality. Both biomarkers (Bio-ADM and PenKid) and clinical scores (SOFA, NEWS and REMS) were good predictors of mortality at 30 days, with Bio-ADM and REMS outperforming the others. Moreover, PenKid resulted in being linked with the worsening of kidney function. Conclusions: In patients presenting with sepsis in the ED, Bio-ADM and PenKid, evaluated with a POCT device, predicted 30-day mortality. These two biomarkers seem even more useful when integrated with clinical risk scores at ED admission. Full article

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11 pages, 926 KiB

Open AccessArticle

Iron Deficiency in Patients with Advanced Heart Failure

by Maria Bakosova, Jan Krejci, Julius Godava, Eva Ozabalova, Hana Poloczkova, Tomas Honek, Peter Hude, Jan Machal, Helena Bedanova, Petr Nemec and Lenka Spinarova

Medicina 2022, 58(11), 1569; https://doi.org/10.3390/medicina58111569 - 31 Oct 2022

Viewed by 1951

Abstract

Background and Objectives: Iron deficiency (ID) is a common comorbidity in patients with heart failure. It is associated with reduced physical performance, frequent hospitalisations for heart failure decompensation, and high cardiovascular and overall mortality. The aim was to determine the prevalence of ID in patients with advanced heart failure on the waiting list for heart transplantation. Methods and Materials: We included 52 patients placed on the waiting list for heart transplantation in 2021 at our centre. The cohort included seven patients with LVAD (left ventricle assist device) as a bridge to transplantation implanted before the time of results collection. In addition to standard tests, the parameters of iron metabolism were monitored. ID was defined as a ferritin value <100 µg/L, or 100–299 µg/L if transferrin saturation (T-sat) is <20%. Results: ID was present in 79% of all subjects, but only in 35% of these patients anaemia was expressed. In the group without LVAD, ID was present in 82%, a median (lower–upper quartile) of ferritin level was 95.4 (62.2–152.1) µg/mL and mean T-sat was 0.18 ± 0.09. In LVAD group, ID was present in 57%, ferritin level was 268 (106–368) µg/mL and mean T-sat was 0.14 ± 0.04. Haemoglobin concentration was the same in patients with or without ID (133 ± 16) vs. (133 ± 23). ID was not associated with anaemia defined with regard to patient’s gender. In 40.5% of cases, iron deficiency was accompanied by chronic renal insufficiency, compared to 12.5% of the patients without ID. In the patients with LVAD, ID was present in four out of seven patients, but the group was too small for reliable statistical testing due to low statistical power. Conclusions: ID was present in the majority of patients with advanced heart failure and was not always accompanied by anaemia and renal insufficiency. Research on optimal markers for the diagnosis of iron deficiency, especially for specific groups of patients with heart failure, is still ongoing. Full article

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10 pages, 1219 KiB

Open AccessArticle

Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up—Data from FAR NHL Registry

by Monika Špinarová, Jindřich Špinar, Lenka Špinarová, Jan Krejčí, Monika Goldbergová-Pávková, Jiří Pařenica, Ondřej Ludka, Filip Málek, Petr Ošťádal, Klára Benešová, Jiří Jarkovský and Karel Lábr

Medicina 2022, 58(10), 1477; https://doi.org/10.3390/medicina58101477 - 18 Oct 2022

Cited by 2 | Viewed by 1508

Abstract

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1–39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40–79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80–119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression. Full article

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16 pages, 3300 KiB

Open AccessArticle

Usefulness of KL-6 for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients

by Mikyoung Park, Mina Hur, Hanah Kim, Chae Hoon Lee, Jong Ho Lee and Minjeong Nam

Medicina 2022, 58(10), 1317; https://doi.org/10.3390/medicina58101317 - 21 Sep 2022

Cited by 3 | Viewed by 1532

Abstract

Background: Krebs von den Lungen 6 (KL-6) is a novel biomarker for interstitial lung disease, and it reflects acute lung injury. We explored the usefulness of KL-6 to predict clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: In a total of 48 hospitalized COVID-19 patients, KL-6 levels were measured using the HISCL KL-6 assay (Sysmex, Kobe, Japan) with the HISCL 5000 automated analyzer (Sysmex). Clinical outcomes (intensive care unit [ICU] admission, ventilator use, extracorporeal membrane oxygenation [ECMO] use, and 30-day mortality) were analyzed according to KL-6 percentiles. Age, initial KL-6 level, Charlson comorbidity index (CCI), and critical disease were compared using the receiver operating characteristic (ROC) curve and Kaplan-Meier methods for clinical outcomes. Results: KL-6 quartiles were associated with ICU admission, ventilator use, and ECMO use (all p < 0.05), except 30-day mortality (p = 0.187). On ROC curve analysis, initial KL-6 level predicted ICU admission, ventilator use, and ECMO use significantly better than age, CCI, and critical disease (all p < 0.05); age, initial KL-6 level, CCI, and critical disease predicted 30-day mortality comparably. On Kaplan–Meier survival analysis, hazard ratios (95% confidence interval) were 4.8 (1.2–19.3) for age, 4.7 (1.1–21.6) for initial KL-6 level, 3.9 (0.9–16.2) for CCI, and 2.1 (0.5–10.3) for critical disease. Conclusions: This study demonstrated that KL-6 could be a useful biomarker to predict clinical outcomes in hospitalized COVID-19 patients. KL-6 may contribute to identifying COVID-19 patients requiring critical care, including ICU admission and ventilator and/or ECMO use. Full article

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20 pages, 1391 KiB

Open AccessSystematic Review

Biochemical Intracystic Biomarkers in the Differential Diagnosis of Pancreatic Cystic Lesions

by Dominika Wietrzykowska-Grishanovich, Ewa Pawlik and Katarzyna Neubauer

Medicina 2022, 58(8), 994; https://doi.org/10.3390/medicina58080994 - 26 Jul 2022

Cited by 1 | Viewed by 2436

Abstract

Background and Objectives: Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also because of the aging of the population. PCLs comprise challenging clinical problems, as their manifestations vary from benign to malignant lesions. Therefore, the recognition of PCLs is achieved through a complex diagnostic and surveillance process, which in turn is usually long-term, invasive, and expensive. Despite the progress made in the identification of novel biomarkers in the cystic fluid that also support the differentiation of PCLs, their application in clinical practice is limited. Materials and Methods: We conducted a systematic review of the literature published in two databases, Pubmed and Embase, on biochemical biomarkers in PCLs that may be applied in the diagnostic algorithms of PCLs. Results: Eleven studies on intracystic glucose, twenty studies on intracystic carcinoembryonic antigen (CEA), and eighteen studies on other biomarkers were identified. Low levels of intracystic glucose had high sensitivity and specificity in the differentiation between mucinous and non-mucinous cystic neoplasms. Conclusions: CEA and glucose are the most widely studied fluid biochemical markers in pancreatic cystic lesions. Glucose has better diagnostic accuracy than CEA. Other biochemical biomarkers require further research. Full article

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7 pages, 289 KiB

Open AccessArticle

Procalcitonin as a Predictive Tool for Death and ICU Admission among Febrile Neutropenic Patients Visiting the Emergency Department

by Christopher J. Coyne, Edward M. Castillo, Rebecca A. Shatsky and Theodore C. Chan

Medicina 2022, 58(8), 985; https://doi.org/10.3390/medicina58080985 - 23 Jul 2022

Cited by 1 | Viewed by 1837

Abstract

Background and Objectives: Risk stratification tools for febrile neutropenia exist but are infrequently utilized by emergency physicians. Procalcitonin may provide emergency physicians with a more objective tool to identify patients at risk of decompensation. Materials and Methods: We conducted a retrospective cohort study evaluating the use of procalcitonin in cases of febrile neutropenia among adult patients presenting to the Emergency Department compared to a non-neutropenic, febrile control group. Our primary outcome measure was in-hospital mortality with a secondary outcome of ICU admission. Results: Among febrile neutropenic patients, a positive initial procalcitonin value was associated with significantly increased odds of inpatient mortality after adjusting for age, sex, race, and ethnicity (AOR 9.912, p < 0.001), which was similar, though greater than, our non-neutropenic cohort (AOR 2.18, p < 0.001). All febrile neutropenic patients with a positive procalcitonin were admitted to the ICU. Procalcitonin had a higher sensitivity and negative predictive value (NPV) in regard to mortality and ICU admission for our neutropenic group versus our non-neutropenic control. Conclusions: Procalcitonin appears to be a valuable tool when attempting to risk stratify patients with febrile neutropenia presenting to the emergency department. Procalcitonin performed better in the prediction of death and ICU admission among patients with febrile neutropenia than a similar febrile, non-neutropenic control group. Full article

11 pages, 303 KiB

Open AccessArticle

High Level of Mid-Regional Proadrenomedullin during ST-Segment Elevation Myocardial Infarction Is an Independent Predictor of Adverse Cardiac Events within 90-Day Follow-Up

by Anggoro Budi Hartopo, Ira Puspitawati and Vita Yanti Anggraeni

Medicina 2022, 58(7), 861; https://doi.org/10.3390/medicina58070861 - 28 Jun 2022

Cited by 1 | Viewed by 1425

Abstract

Background and Objectives: the cardiovascular adverse events including mortality and heart failure, persist significantly during the first months after the acute phase of ST-segment elevation myocardial infarction (STEMI). The increased level of midregional proadrenomedullin (MR-proADM), at hospital presentation in STEMI patients is considered an independent predictor of short-term and long-term mortality and heart failure. This study aimed to measure MR-proADM levels during the acute and recovery phases of STEMI and corroborate whether MR-proADM level was associated with the adverse cardiac events after recovering from STEMI. Materials and Methods: this prospective study enrolled subjects with acute phase STEMI admitted to the intensive cardiac care unit. After recovering and discharged from hospitalization, subjects were followed-up for 90 days. For MR-proADM measurement, the blood samples during acute phase were withdrawn on hospital admission (MR-proADM-0) and during recovery at the day-30 follow up (MR-proADM-30). Adverse cardiac events were evaluated at 30-day and 90-day follow up, namely a composite of death, chronic heart failure, and hospital readmission of any cardiac causes. Results: 83 subjects were enrolled. The median MR-proADM-0 was 3313.33 pg/mL and MR-proADM-30 was significantly reduced at 292.50 pg/mL, p < 0.001. Nineteen subjects (22.9%) experienced adverse cardiac events at 30-day follow up. The MR-proADM-0 level was independently associated with 30-day adverse cardiac events (adjustedOR 1.002, 95%CI: 1.001–1.003, p = 0.040), after adjustment with other variables. In this case, 25 subjects (32.5%) experienced adverse cardiac events at 90-day follow-up. The MR-proADM-0 level was independently associated with 90-day adverse cardiac events (adjustedOR 1.002, 95%CI: 1.001–1.003, p = 0.049). The higher changes of MR-proADM-0 to MR-proADM-30 also associated with adverse cardiac events at 90 days. Conclusions: The MR-proADM was significantly increased during the acute phase of STEMI and declined during recovery phase. The higher MR-proADM level during the acute phase of STEMI and its change intensity were predictors of adverse cardiac events within the 90-day follow up. Full article

20 pages, 3250 KiB

Open AccessArticle

Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease

by Elena Maria Domsa, Ioana Berindan-Neagoe, Livia Budisan, Cornelia Braicu, Ioana Para, Alina Ioana Tantau, Olga Hilda Orasan, Lidia Ciobanu, Teodora Atena Pop, Gabriela Adriana Filip, Nicoleta Leach, Vasile Negrean, Daniela Matei and Vasile Andreica

Medicina 2022, 58(2), 180; https://doi.org/10.3390/medicina58020180 - 25 Jan 2022

Cited by 4 | Viewed by 2803

Abstract

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice. Full article

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The Utility of Biomarkers in Disease Management Approach

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