Research

17 pages, 1827 KiB

Open AccessArticle

Second-Line Treatment of Metastatic Renal Cell Carcinoma in the Era of Predictive Biomarkers

by Andreea Ioana Parosanu, Catalin Baston, Ioana Miruna Stanciu, Cristina Florina Parlog and Cornelia Nitipir

Diagnostics 2023, 13(14), 2430; https://doi.org/10.3390/diagnostics13142430 - 20 Jul 2023

Cited by 3 | Viewed by 1905

Abstract

Background: Over the past few years, significant advancements have been achieved in the front-line treatment of metastatic renal cell carcinomas (mRCCs). However, most patients will eventually encounter disease progression during this front-line treatment and require further therapeutic options. While treatment choices for mRCCs [...] Read more.

Background: Over the past few years, significant advancements have been achieved in the front-line treatment of metastatic renal cell carcinomas (mRCCs). However, most patients will eventually encounter disease progression during this front-line treatment and require further therapeutic options. While treatment choices for mRCCs patients are determined by established risk classification models, knowledge of prognostic factors in subsequent line therapy is essential in patient care. Methods: In this retrospective, single-center study, patients diagnosed with mRCCs who experienced progression after first-line therapy were enrolled. Fifteen factors were analyzed for their prognostic impact on survival using the Kaplan–Meier method and the Cox proportional hazards model. Results: Poor International Metastatic RCCs Database Consortium (IMDC) and Memorial Sloan-Kettering Cancer Center (MSKCC) risk scores, NLR value > 3, clinical benefit < 3 months from a therapeutic line, and the presence of sarcomatoid differentiation were found to be poor independent prognostic factors for shortened overall survival. Conclusions: This study provided new insights into the identification of potential prognostic parameters for late-line treatment in mRCCs. The results indicated that good IMDC and MSKCC prognostic scores are effective in second-line therapy. Moreover, patients with NLR < 3, no sarcomatoid differentiation, and clinical benefit > 3 months experienced significantly longer overall survival. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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13 pages, 3584 KiB

Open AccessArticle

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

by Velizar Shivarov, Georgi Blazhev and Angel Yordanov

Diagnostics 2023, 13(9), 1556; https://doi.org/10.3390/diagnostics13091556 - 26 Apr 2023

Viewed by 1254

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three [...] Read more.

Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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15 pages, 1178 KiB

Open AccessArticle

Diagnostic and Prognostic Nomograms for Hepatocellular Carcinoma Based on PIVKA-II and Serum Biomarkers

by Shu An, Xiaoxia Zhan, Min Liu, Laisheng Li and Jian Wu

Diagnostics 2023, 13(8), 1442; https://doi.org/10.3390/diagnostics13081442 - 17 Apr 2023

Cited by 2 | Viewed by 1678

Abstract

Background: The aim of the present study was to develop an improved diagnostic and prognostic model for HBV-associated HCC by combining AFP with PIVKA-II and other potential serum/plasma protein biomarkers. Methods: A total of 578 patients, including 352 patients with HBV-related HCC, 102 [...] Read more.

Background: The aim of the present study was to develop an improved diagnostic and prognostic model for HBV-associated HCC by combining AFP with PIVKA-II and other potential serum/plasma protein biomarkers. Methods: A total of 578 patients, including 352 patients with HBV-related HCC, 102 patients with HBV-associated liver cirrhosis (LC), 124 patients with chronic HBV, and 127 healthy subjects (HS), were enrolled in the study. The serum levels of AFP, PIVKA-II, and other laboratory parameters were collected. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors, respectively. The diagnostic efficacy of the nomogram was evaluated using receiver operator curve (ROC) analysis and the prognostic performance was measured by Harrell’s concordance index (C-index). Results: AFP and PIVKA-II levels were significantly increased in HBV-related HCC, compared with those in HBV-associated LC and chronic HBV participants (p < 0.05 and p < 0.001, respectively). The diagnostic nomogram, which included age, gender, AFP, PIVKA-II, prothrombin time (PT), and total protein (TP), discriminated patients with HBV-HCC from those with HBV-LC or chronic HBV with an AUC of 0.970. In addition, based on the univariate and multivariate Cox regression analysis, PIVKA-II, γ-glutamyl transpeptidase, and albumin were found to be significantly associated with the prognosis of HBV-related HCC and were incorporated into a nomogram. The C-index of the nomogram for predicting 3-year survival in the training and validation groups was 0.75 and 0.78, respectively. The calibration curves for the probability of 3-year OS showed good agreement between the nomogram prediction and the actual observation in the training and the validation groups. Furthermore, the nomogram had a higher C-index (0.74) than that of the Child−Pugh grade (0.62), the albumin−bilirubin (ALBI) score (0.64), and Barcelona Clinic Liver Cancer (0.56) in all follow-up cases. Conclusion: Our study suggests that the nomograms based on AFP, PIVKA-II, and potential serum protein biomarkers showed a better performance in the diagnosis and prognosis of HCC, which may help to guide therapeutic strategies and assess the prognosis of HCC. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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17 pages, 3883 KiB

Open AccessArticle

miR-146a, miR-221, and miR-155 are Involved in Inflammatory Immune Response in Severe COVID-19 Patients

by Noemí Gaytán-Pacheco, Alejandro Ibáñez-Salazar, Ana Sofía Herrera-Van Oostdam, Juan José Oropeza-Valdez, Martín Magaña-Aquino, Jesús Adrián López, Joel Monárrez-Espino and Yamilé López-Hernández

Diagnostics 2023, 13(1), 133; https://doi.org/10.3390/diagnostics13010133 - 30 Dec 2022

Cited by 12 | Viewed by 2031

Abstract

COVID-19 infection triggered a global public health crisis during the 2020–2022 period, and it is still evolving. This highly transmissible respiratory disease can cause mild symptoms up to severe pneumonia with potentially fatal respiratory failure. In this cross-sectional study, 41 PCR-positive patients for [...] Read more.

COVID-19 infection triggered a global public health crisis during the 2020–2022 period, and it is still evolving. This highly transmissible respiratory disease can cause mild symptoms up to severe pneumonia with potentially fatal respiratory failure. In this cross-sectional study, 41 PCR-positive patients for SARS-CoV-2 and 42 healthy controls were recruited during the first wave of the pandemic in Mexico. The plasmatic expression of five circulating miRNAs involved in inflammatory and pathological host immune responses was assessed using RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction). Compared with controls, a significant upregulation of miR-146a, miR-155, and miR-221 was observed; miR-146a had a positive correlation with absolute neutrophil count and levels of brain natriuretic propeptide (proBNP), and miR-221 had a positive correlation with ferritin and a negative correlation with total cholesterol. We found here that CDKN1B gen is a shared target of miR-146a, miR-221-3p, and miR-155-5p, paving the way for therapeutic interventions in severe COVID-19 patients. The ROC curve built with adjusted variables (miR-146a, miR-221-3p, miR-155-5p, age, and male sex) to differentiate individuals with severe COVID-19 showed an AUC of 0.95. The dysregulation of circulating miRNAs provides new insights into the underlying immunological mechanisms, and their possible use as biomarkers to discriminate against patients with severe COVID-19. Functional analysis showed that most enriched pathways were significantly associated with processes related to cell proliferation and immune responses (innate and adaptive). Twelve of the predicted gene targets have been validated in plasma/serum, reflecting their potential use as predictive prognosis biomarkers. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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15 pages, 280 KiB

Open AccessArticle

COVID-19 Patients in the COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx

by Anna Eligulashvili, Megan Darrell, Carolyn Miller, Jeylin Lee, Seth Congdon, Jimmy S. Lee, Kevin Hsu, Judy Yee, Wei Hou, Marjan Islam and Tim Q. Duong

Diagnostics 2023, 13(1), 119; https://doi.org/10.3390/diagnostics13010119 - 30 Dec 2022

Cited by 9 | Viewed by 1544

Abstract

Background: Early in the pandemic, we established COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx and implemented a detailed evaluation protocol to assess physical, emotional, and cognitive function, pulmonary function tests, and imaging for COVID-19 survivors. Here, we report our findings up [...] Read more.

Background: Early in the pandemic, we established COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx and implemented a detailed evaluation protocol to assess physical, emotional, and cognitive function, pulmonary function tests, and imaging for COVID-19 survivors. Here, we report our findings up to five months post-acute COVID-19. Methods: Main outcomes and measures included pulmonary function tests, imaging tests, and a battery of symptom, physical, emotional, and cognitive assessments 5 months post-acute COVID-19. Findings: Dyspnea, fatigue, decreased exercise tolerance, brain fog, and shortness of breath were the most common symptoms but there were generally no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Many patients had abnormal physical, emotional, and cognitive scores, but most functioned independently; there were no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Six-minute walk tests, lung ultrasound, and diaphragm excursion were abnormal but only in the hospitalized cohort. Pulmonary function tests showed moderately restrictive pulmonary function only in the hospitalized cohort but no obstructive pulmonary function. Newly detected major neurological events, microvascular disease, atrophy, and white-matter changes were rare, but lung opacity and fibrosis-like findings were common after acute COVID-19. Interpretation: Many COVID-19 survivors experienced moderately restrictive pulmonary function, and significant symptoms across the physical, emotional, and cognitive health domains. Newly detected brain imaging abnormalities were rare, but lung imaging abnormalities were common. This study provides insights into post-acute sequelae following SARS-CoV-2 infection in neurological and pulmonary systems which may be used to support at-risk patients and develop effective screening methods and interventions. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

10 pages, 1555 KiB

Open AccessArticle

Application of Procalcitonin for the Rapid Diagnosis of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease

by Shuhua Xie, Peisong Chen, Dong Wang, Xiaobing Jiang, Zhongwen Wu, Kang Liao, Min Liu, Shihong Zhang and Yili Chen

Diagnostics 2022, 12(12), 3108; https://doi.org/10.3390/diagnostics12123108 - 09 Dec 2022

Viewed by 1104

Abstract

Background: The incidence of Clostridioides difficile infection (CDI) has increased in recent years in patients with inflammatory bowel disease (IBD). C. difficile is a toxin-producing bacterium, and CDI results in the worsening of underlying IBD, increasing the risk of IBD treatment failure, [...] Read more.

Background: The incidence of Clostridioides difficile infection (CDI) has increased in recent years in patients with inflammatory bowel disease (IBD). C. difficile is a toxin-producing bacterium, and CDI results in the worsening of underlying IBD, increasing the risk of IBD treatment failure, surgery, and hospitalization. Because the symptoms of CDI overlap with those of IBD, it is challenging to make a differential diagnosis. Therefore, early, rapid, and reliable diagnostic tools that can identify CDI in IBD patients would be valuable to clinicians. Methods: This study retrospectively collected 135 patients with IBD. Among them, 44 patients were diagnosed with CDI, and 42 patients were diagnosed with viral or fungal infections. A total of 49 patients without infections were defined as the control group. The diagnostic values of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count in the peripheral blood were examined. Results: In this study, PCT levels were significantly higher in patients with CDI than in non-CDI patients (including patients with viral/fungal infections and the control group; p < 0.001 and p < 0.05, respectively). CRP levels were significantly higher in patients with CDI than in non-CDI patients (p < 0.05). The area under the curve (AUC) of PCT and WBC count were compared using DeLong’s test: the AUCs of PCT vs. CRP for the detection of the IBD–CDI group and the control group was 0.826 [95% confidence interval (CI) 0.743–0.909] vs. 0.663 [95% confidence interval (CI) 0.551–0.774] (p < 0.05), respectively. WBC count was inferior as a diagnostic tool for CDI. The sensitivity was 59.09% (95% CI: 43.2% to 73.7%), the specificity was 89.80% (95% CI: 77.8% to 96.6%), and the positive likelihood ratio LR (+) was 5.79 for PCT for the diagnosis of CDI. Conclusions: The present study demonstrates the superiority of PCT over CRP and WBC count for the rapid diagnosis of CDI in IBD patients. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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14 pages, 4678 KiB

Open AccessArticle

Identification and Application of a Novel Immune-Related lncRNA Signature on the Prognosis and Immunotherapy for Lung Adenocarcinoma

by Zhimin Zeng, Yuxia Liang, Jia Shi, Lisha Xiao, Lu Tang, Yubiao Guo, Fengjia Chen and Gengpeng Lin

Diagnostics 2022, 12(11), 2891; https://doi.org/10.3390/diagnostics12112891 - 21 Nov 2022

Cited by 2 | Viewed by 1445

Abstract

Background: Long non-coding RNA (lncRNA) participates in the immune regulation of lung cancer. However, limited studies showed the potential roles of immune-related lncRNAs (IRLs) in predicting survival and immunotherapy response of lung adenocarcinoma (LUAD). Methods: Based on The Cancer Genome Atlas (TCGA) and [...] Read more.

Background: Long non-coding RNA (lncRNA) participates in the immune regulation of lung cancer. However, limited studies showed the potential roles of immune-related lncRNAs (IRLs) in predicting survival and immunotherapy response of lung adenocarcinoma (LUAD). Methods: Based on The Cancer Genome Atlas (TCGA) and ImmLnc databases, IRLs were identified through weighted gene coexpression network analysis (WGCNA), Cox regression, and Lasso regression analyses. The predictive ability was validated by Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves in the internal dataset, external dataset, and clinical study. The immunophenoscore (IPS)-PD1/PD-L1 blocker and IPS-CTLA4 blocker data of LUAD were obtained in TCIA to predict the response to immune checkpoint inhibitors (ICIs). The expression levels of immune checkpoint molecules and markers for hyperprogressive disease were analyzed. Results: A six-IRL signature was identified, and patients were stratified into high- and low-risk groups. The low-risk had improved survival outcome (p = 0.006 in the training dataset, p = 0.010 in the testing dataset, p < 0.001 in the entire dataset), a stronger response to ICI (p < 0.001 in response to anti-PD-1/PD-L1, p < 0.001 in response to anti-CTLA4), and higher expression levels of immune checkpoint molecules (p < 0.001 in PD-1, p < 0.001 in PD-L1, p < 0.001 in CTLA4) but expressed more biomarkers of hyperprogression in immunotherapy (p = 0.002 in MDM2, p < 0.001 in MDM4). Conclusion: The six-IRL signature exhibits a promising prediction value of clinical prognosis and ICI efficacy in LUAD. Patients with low risk might gain benefits from ICI, although some have a risk of hyperprogressive disease. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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24 pages, 19876 KiB

Open AccessArticle

Metabolomic Selection in the Progression of Type 2 Diabetes Mellitus: A Genetic Algorithm Approach

by Jorge Morgan-Benita, Ana G. Sánchez-Reyna, Carlos H. Espino-Salinas, Juan José Oropeza-Valdez, Huizilopoztli Luna-García, Carlos E. Galván-Tejada, Jorge I. Galván-Tejada, Hamurabi Gamboa-Rosales, Jose Antonio Enciso-Moreno and José Celaya-Padilla

Diagnostics 2022, 12(11), 2803; https://doi.org/10.3390/diagnostics12112803 - 15 Nov 2022

Cited by 2 | Viewed by 1510

Abstract

According to the World Health Organization (WHO), type 2 diabetes mellitus (T2DM) is a result of the inefficient use of insulin by the body. More than 95% of people with diabetes have T2DM, which is largely due to excess weight and physical inactivity. [...] Read more.

According to the World Health Organization (WHO), type 2 diabetes mellitus (T2DM) is a result of the inefficient use of insulin by the body. More than 95% of people with diabetes have T2DM, which is largely due to excess weight and physical inactivity. This study proposes an intelligent feature selection of metabolites related to different stages of diabetes, with the use of genetic algorithms (GA) and the implementation of support vector machines (SVMs), K-Nearest Neighbors (KNNs) and Nearest Centroid (NEARCENT) and with a dataset obtained from the Instituto Mexicano del Seguro Social with the protocol name of the following: “Análisis metabolómico y transcriptómico diferencial en orina y suero de pacientes pre diabéticos, diabéticos y con nefropatía diabética para identificar potenciales biomarcadores pronósticos de daño renal” (differential metabolomic and transcriptomic analyses in the urine and serum of pre-diabetic, diabetic and diabetic nephropathy patients to identify potential prognostic biomarkers of kidney damage). In order to analyze which machine learning (ML) model is the most optimal for classifying patients with some stage of T2DM, the novelty of this work is to provide a genetic algorithm approach that detects significant metabolites in each stage of progression. More than 100 metabolites were identified as significant between all stages; with the data analyzed, the average accuracies obtained in each of the five most-accurate implementations of genetic algorithms were in the range of 0.8214–0.9893 with respect to average accuracy, providing a precise tool to use in detections and backing up a diagnosis constructed entirely with metabolomics. By providing five potential biomarkers for progression, these extremely significant metabolites are as follows: “Cer(d18:1/24:1) i2”, “PC(20:3-OH/P-18:1)”, “Ganoderic acid C2”, “TG(16:0/17:1/18:1)” and “GPEtn(18:0/20:4)”. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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12 pages, 2370 KiB

Open AccessArticle

Radiomics Based on Nomogram Predict Pelvic Lymphnode Metastasis in Early-Stage Cervical Cancer

by Xueming Xia, Dongdong Li, Wei Du, Yu Wang, Shihong Nie, Qiaoyue Tan and Qiheng Gou

Diagnostics 2022, 12(10), 2446; https://doi.org/10.3390/diagnostics12102446 - 10 Oct 2022

Cited by 3 | Viewed by 1958

Abstract

The accurate prediction of the status of PLNM preoperatively plays a key role in treatment strategy decisions in early-stage cervical cancer. The aim of this study was to develop and validate a radiomics-based nomogram for the preoperative prediction of pelvic lymph node metastatic [...] Read more.

The accurate prediction of the status of PLNM preoperatively plays a key role in treatment strategy decisions in early-stage cervical cancer. The aim of this study was to develop and validate a radiomics-based nomogram for the preoperative prediction of pelvic lymph node metastatic status in early-stage cervical cancer. One hundred fifty patients were enrolled in this study. Radiomics features were extracted from T2-weighted MRI imaging (T2WI). Based on the selected features, a support vector machine (SVM) algorithm was used to build the radiomics signature. The radiomics-based nomogram was developed incorporating radiomics signature and clinical risk factors. In the training cohort (AUC = 0.925, accuracy = 81.6%, sensitivity = 70.3%, and specificity = 92.0%) and the testing cohort (AUC = 0.839, accuracy = 74.2%, sensitivity = 65.7%, and specificity = 82.8%), clinical models that combine stromal invasion depth, FIGO stage, and MTD perform poorly. The combined model had the highest AUC in the training cohort (AUC = 0.988, accuracy = 95.9%, sensitivity = 92.0%, and specificity = 100.0%) and the testing cohort (AUC = 0.922, accuracy = 87.1%, sensitivity = 85.7%, and specificity = 88.6%) when compared to the radiomics and clinical models. The study may provide valuable guidance for clinical physicians regarding the treatment strategies for early-stage cervical cancer patients. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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10 pages, 1568 KiB

Open AccessArticle

Clinical Value of Neutrophil CD64 Index, PCT, and CRP in Acute Pancreatitis Complicated with Abdominal Infection

by Biao Wang, Rongzhu Tang, Shaohong Wu, Ming Liu, Fariha Kanwal, Muhammad Fayyaz ur Rehman, Fang Wu and Jianping Zhu

Diagnostics 2022, 12(10), 2409; https://doi.org/10.3390/diagnostics12102409 - 05 Oct 2022

Cited by 4 | Viewed by 1429

Abstract

Objective: To study the clinical diagnostic value of neutrophil CD64 index, PCT, and CRP in patients with acute pancreatitis with abdominal infection. Methods: A number of patients with acute pancreatitis (n = 234) participated in the study. According to the infection and [...] Read more.

Objective: To study the clinical diagnostic value of neutrophil CD64 index, PCT, and CRP in patients with acute pancreatitis with abdominal infection. Methods: A number of patients with acute pancreatitis (n = 234) participated in the study. According to the infection and health conditions, they were further divided into the non-infection group (n = 122), infection group (n = 78), and sepsis group (n = 34), and 40 healthy subjects were selected in the control group (n = 40). Expression levels of infection indexes, such as CD64 index, PCT, and CRP, were detected and compared. ROC curves were drawn to compare the efficacy of each index in the diagnosis of acute pancreatitis with abdominal infection and sepsis. The study was retrospectively registered under the China Clinical Trial Registry as a trial number ChiCTR2100054308. Results: All indexes were significantly higher in three clinical groups than the healthy control group (p < 0.05). The CD64 index, CD64 positive rate, and PCT in the infected group were significantly higher than those in the uninfected group (ALL p < 0.05). The PCT of patients infected with Gram-negative bacteria was significantly higher than that of Gram-positive bacteria-infected patients (p < 0.05). CD64 index had the best diagnostic efficiency for acute pancreatitis infection, with 82.14% sensitivity, 88.51% specificity, and 0.707 Youden indexes. The CD64 Youden index (0.780) for sepsis diagnosis was the highest, while the AUC of PCT was the highest (0.897). Conclusion: CD64 index combined with PCT has good sensitivity and specificity in diagnosing acute pancreatitis infection and sepsis. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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14 pages, 793 KiB

Open AccessArticle

Predictive Value of MR-proADM in the Risk Stratification and in the Adequate Care Setting of COVID-19 Patients Assessed at the Triage of the Emergency Department

by Marilena Minieri, Vito N. Di Lecce, Maria Stella Lia, Massimo Maurici, Francesca Leonardis, Susanna Longo, Luca Colangeli, Carla Paganelli, Stefania Levantesi, Alessandro Terrinoni, Vincenzo Malagnino, Domenico J. Brunetti, Alfredo Giovannelli, Massimo Pieri, Marco Ciotti, Cartesio D’Agostini, Mariachiara Gabriele, Sergio Bernardini and Jacopo M. Legramante

Diagnostics 2022, 12(8), 1971; https://doi.org/10.3390/diagnostics12081971 - 15 Aug 2022

Cited by 3 | Viewed by 1145

Abstract

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to [...] Read more.

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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13 pages, 2061 KiB

Open AccessArticle

Postpartum Assessment of the Correlation between Serum Hormone Levels of Estradiol, Progesterone, Prolactin and ß-HCG and Blood Pressure Measurements in Pre-Eclampsia Patients

by Mariz Kasoha, Zoltan Takacs, Jacob Dumé, Sebastian Findeklee, Christoph Gerlinger, Romina-Marina Sima, Liana Ples, Erich-Franz Solomayer and Bashar Haj Hamoud

Diagnostics 2022, 12(7), 1700; https://doi.org/10.3390/diagnostics12071700 - 12 Jul 2022

Viewed by 1940

Abstract

Background: Preeclampsia is a pregnancy-related hypertensive disease. Aberrant hormone levels have been implicated in blood pressure disorders. This study investigated the association of postpartum maternal serum hormone levels of estradiol, progesterone, prolactin, and ß-HCG with poorer PE-related complications including arterial hypertension. Methods: Thirty [...] Read more.

Background: Preeclampsia is a pregnancy-related hypertensive disease. Aberrant hormone levels have been implicated in blood pressure disorders. This study investigated the association of postpartum maternal serum hormone levels of estradiol, progesterone, prolactin, and ß-HCG with poorer PE-related complications including arterial hypertension. Methods: Thirty patient women with preeclampsia, and twenty women with uncomplicated pregnancy were included in this study. Serum levels of estradiol, progesterone, prolactin, and ß-HCG were determined immediately after delivery, and on the first and third postpartum days by means of ECLIA. Results: Compared with normal pregnancy cases, preeclampsia cases had higher serum levels of ß-HCG levels on Day-0 (319%), of progesterone on Day-0 (207%) and Day-1 (178%), and of estradiol on Day-1 (187%) and Day-3 (185%). Increased prolactin levels were positively associated with disease severity and estradiol and progesterone levels were decreased in poorer preeclampsia features including disease onset and IUGR diagnosis. No significant correlation between different hormone levels and blood pressure measurements was reported. Conclusions: This study is the first that detected postpartum maternal serum hormone levels and their correlation with blood pressure measurements in preeclampsia. We believe that the persistent arterial hypertension in the puerperium in preeclampsia as well as poorer disease specifications are most likely not of hormonal origin. Larger, well-defined prospective studies are recommended. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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Review

Jump to: Research, Other

13 pages, 694 KiB

Open AccessReview

Biofluid Biomarkers in the Prognosis of Chronic Subdural Hematoma: A Systematic Scoping Review

by Georgios Georgountzos, Ioannis Gkalonakis, Lykourgos Anastasopoulos, George Stranjalis and Theodosis Κalamatianos

Diagnostics 2023, 13(14), 2449; https://doi.org/10.3390/diagnostics13142449 - 22 Jul 2023

Viewed by 1127

Abstract

The present systematic scoping review aimed at mapping and analyzing the available literature on biological fluid (biofluid) biomarkers showing promise in the prediction of chronic subdural hematoma (cSDH) recurrence and the prognosis of neurological/functional patient outcome. Twenty-three studies published between 2003 and 2023 [...] Read more.

The present systematic scoping review aimed at mapping and analyzing the available literature on biological fluid (biofluid) biomarkers showing promise in the prediction of chronic subdural hematoma (cSDH) recurrence and the prognosis of neurological/functional patient outcome. Twenty-three studies published between 2003 and 2023 investigating a diverse range of biomarkers in hematoma fluid and/or the circulation in 3749 patients were included. Immune cell populations and inflammatory/anti-inflammatory cytokines comprised the most studied category of biomarkers displaying significant findings. A notable time trend in biomarker studies was a recent shift in research focus towards the analysis of circulating biomarkers. Several biomarkers were indicated as independent predictors of cSDH recurrence and/or functional/neurological outcome, including circulating fibrinogen degradation products (FDP), brain natriuretic peptide (BNP-1) and high-density lipoprotein (HDL), as well as blood urea nitrogen (BUN) and the ratios of blood neutrophil to lymphocyte (NLR) or red blood cell distribution width to platelet count (RPR). While studies on cSDH prognostic biomarkers have gained, in recent years, momentum, additional multicenter prospective studies are warranted to confirm and extend their findings. The identification of prognostic biofluid biomarkers in cSDH is an active field of research that may provide future tools, guiding clinical decisions and allowing for the design of treatments based on risk stratification. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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13 pages, 649 KiB

Open AccessReview

Molecular Biomarkers in Perthes Disease: A Review

by Vesna Spasovski, Sanja Srzentić Dražilov, Gordana Nikčević, Zoran Baščarević, Maja Stojiljković, Sonja Pavlović and Duško Spasovski

Diagnostics 2023, 13(3), 471; https://doi.org/10.3390/diagnostics13030471 - 27 Jan 2023

Cited by 3 | Viewed by 1553

Abstract

Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology [...] Read more.

Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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23 pages, 1668 KiB

Open AccessReview

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods

by Ena Gupta, Juhi Saxena, Sanni Kumar, Umang Sharma, Saundarya Rastogi, Vijay Kumar Srivastava, Sanket Kaushik and Anupam Jyoti

Diagnostics 2023, 13(2), 277; https://doi.org/10.3390/diagnostics13020277 - 11 Jan 2023

Cited by 6 | Viewed by 6333

Abstract

Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of [...] Read more.

Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of AMR is through the active detection and identification of the pathogen along with the quantification of resistance. For better management of such disease, there is an essential requirement to approach many suitable diagnostic techniques for the proper administration of antibiotics and elimination of these infectious diseases. The current method employed for the diagnosis of sepsis relies on the conventional culture of blood suspected infection. However, this method is more time consuming and generates results that are false negative in the case of antibiotic pretreated samples as well as slow-growing microbes. In comparison to the conventional method, modern methods are capable of analyzing blood samples, obtaining accurate results from the suspicious patient of sepsis, and giving all the necessary information to identify the pathogens as well as AMR in a short period. The present review is intended to highlight the culture shift from conventional to modern and advanced technologies including their limitations for the proper and prompt diagnosing of bloodstream infections and AMR detection. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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16 pages, 356 KiB

Open AccessReview

Nectins and Nectin-like Molecules in Colorectal Cancer: Role in Diagnostics, Prognostic Values, and Emerging Treatment Options: A Literature Review

by Jakub Kobecki, Paweł Gajdzis, Grzegorz Mazur and Mariusz Chabowski

Diagnostics 2022, 12(12), 3076; https://doi.org/10.3390/diagnostics12123076 - 07 Dec 2022

Cited by 2 | Viewed by 1490

Abstract

In 2020, colorectal cancer was the third most common type of cancer worldwide with a clearly visible increase in the number of cases each year. With relatively high mortality rates and an uncertain prognosis, colorectal cancer is a serious health problem. There is [...] Read more.

In 2020, colorectal cancer was the third most common type of cancer worldwide with a clearly visible increase in the number of cases each year. With relatively high mortality rates and an uncertain prognosis, colorectal cancer is a serious health problem. There is an urgent need to investigate its specific mechanism of carcinogenesis and progression in order to develop new strategies of action against this cancer. Nectins and Nectin-like molecules are cell adhesion molecules that take part in a plethora of essential processes in healthy tissues as well as mediating substantial actions for tumor initiation and evolution. Our understanding of their role and a viable application of this in anti-cancer therapy has rapidly improved in recent years. This review summarizes the current data on the role nectins and Nectin-like molecules play in colorectal cancer. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

27 pages, 1566 KiB

Open AccessReview

Bronchoalveolar Lavage Fluid-Isolated Biomarkers for the Diagnostic and Prognostic Assessment of Lung Cancer

by Alexandros Kalkanis, Dimitrios Papadopoulos, Dries Testelmans, Alexandra Kopitopoulou, Eva Boeykens and Els Wauters

Diagnostics 2022, 12(12), 2949; https://doi.org/10.3390/diagnostics12122949 - 25 Nov 2022

Cited by 8 | Viewed by 1798

Abstract

Lung cancer is considered one of the most fatal malignant neoplasms because of its late detection. Detecting molecular markers in samples from routine bronchoscopy, including many liquid-based cytology procedures, such as bronchoalveolar lavage fluid (BALF), could serve as a favorable technique to enhance [...] Read more.

Lung cancer is considered one of the most fatal malignant neoplasms because of its late detection. Detecting molecular markers in samples from routine bronchoscopy, including many liquid-based cytology procedures, such as bronchoalveolar lavage fluid (BALF), could serve as a favorable technique to enhance the efficiency of a lung cancer diagnosis. BALF analysis is a promising approach to evaluating the tumor progression microenvironment. BALF’s cellular and non-cellular components dictate the inflammatory response in a cancer-proliferating microenvironment. Furthermore, it is an essential material for detecting clinically significant predictive and prognostic biomarkers that may aid in guiding treatment choices and evaluating therapy-induced toxicities in lung cancer. In the present article, we have reviewed recent literature about the utility of BALF analysis for detecting markers in different stages of tumor cell metabolism, employing either specific biomarker assays or broader omics approaches. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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9 pages, 1078 KiB

Open AccessCase Report

IDH Mutations Are Potentially the Intrinsic Genetic Link among the Multiple Neoplastic Lesions in Ollier Disease and Maffucci Syndrome: A Clinicopathologic Analysis from a Single Institute in Shanghai, China

by Chunyan Chen, Jian Li, Ting Jiang, Juan Tang, Zhichang Zhang, Yanli Luo, Xinpei Wang, Keyang Sun, Zhiming Jiang, Juan Zhou and Zhiyan Liu

Diagnostics 2022, 12(11), 2764; https://doi.org/10.3390/diagnostics12112764 - 11 Nov 2022

Cited by 1 | Viewed by 1490

Abstract

Background: This study aims to investigate isocitrate dehydrogenase gene mutations in patients with the non-hereditary skeletal disorders of Ollier disease and Maffucci syndrome, particularly in the extraosseous tumours. Methods: A total of 16 tumours from three patients with Ollier disease and three patients [...] Read more.

Background: This study aims to investigate isocitrate dehydrogenase gene mutations in patients with the non-hereditary skeletal disorders of Ollier disease and Maffucci syndrome, particularly in the extraosseous tumours. Methods: A total of 16 tumours from three patients with Ollier disease and three patients with Maffucci syndrome were collected. Sanger sequencing was applied to determine the hotspot mutations of IDH1 and IDH2 genes in multiple neoplastic tissues. Results: A majority of the tumours displayed an IDH1 mutation (p.R132C in 11 tumours including the paediatric ovarian tumour from one patient with Ollier disease, 4 cutaneous haemangiomas from three patients with Maffucci syndrome, 5 enchondromas and 1 chondrosarcoma; p.R132H in 2 cartilaginous tumours from one patient). Conclusions: IDH1 mutations were demonstrated in multiple cartilaginous tumours and extraskeletal neoplasms in this case series. Specifically, identical IDH1 mutations were confirmed in the separate lesions of each patient. These results are in concordance with findings that have been reported. However, here, we additionally reported the first case of Ollier disease with an ovarian tumour, which harboured the identical IDH1 mutation with the corresponding cartilaginous tumour. We further provided evidence that IDH mutations are the potential genetic links among the multiple neoplastic lesions of Ollier disease and Maffucci syndrome. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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17 pages, 2734 KiB

Open AccessSystematic Review

Early Prediction and Monitoring of Treatment Response in Gastrointestinal Stromal Tumors by Means of Imaging: A Systematic Review

by Ylva. A. Weeda, Gijsbert M. Kalisvaart, Floris H. P. van Velden, Hans Gelderblom, Aart. J. van der Molen, Judith V. M. G. Bovee, Jos A. van der Hage, Willem Grootjans and Lioe-Fee de Geus-Oei

Diagnostics 2022, 12(11), 2722; https://doi.org/10.3390/diagnostics12112722 - 07 Nov 2022

Cited by 2 | Viewed by 1913

Abstract

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms. Tyrosine kinase inhibitor (TKI) therapy is currently part of routine clinical practice for unresectable and metastatic disease. It is important to assess the efficacy of TKI treatment at an early stage to optimize therapy strategies [...] Read more.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms. Tyrosine kinase inhibitor (TKI) therapy is currently part of routine clinical practice for unresectable and metastatic disease. It is important to assess the efficacy of TKI treatment at an early stage to optimize therapy strategies and eliminate futile ineffective treatment, side effects and unnecessary costs. This systematic review provides an overview of the imaging features obtained from contrast-enhanced (CE)-CT and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) PET/CT to predict and monitor TKI treatment response in GIST patients. PubMed, Web of Science, the Cochrane Library and Embase were systematically screened. Articles were considered eligible if quantitative outcome measures (area under the curve (AUC), correlations, sensitivity, specificity, accuracy) were used to evaluate the efficacy of imaging features for predicting and monitoring treatment response to various TKI treatments. The methodological quality of all articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies, v2 (QUADAS-2) tool and modified versions of the Radiomics Quality Score (RQS). A total of 90 articles were included, of which 66 articles used baseline [¹⁸F]FDG-PET and CE-CT imaging features for response prediction. Generally, the presence of heterogeneous enhancement on baseline CE-CT imaging was considered predictive for high-risk GISTs, related to underlying neovascularization and necrosis of the tumor. The remaining articles discussed therapy monitoring. Clinically established imaging features, including changes in tumor size and density, were considered unfavorable monitoring criteria, leading to under- and overestimation of response. Furthermore, changes in glucose metabolism, as reflected by [¹⁸F]FDG-PET imaging features, preceded changes in tumor size and were more strongly correlated with tumor response. Although CE-CT and [¹⁸F]FDG-PET can aid in the prediction and monitoring in GIST patients, further research on cost-effectiveness is recommended. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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14 pages, 952 KiB

Open AccessProtocol

Early Diagnosis of Chemotherapy-Linked Cardiotoxicity in Breast Cancer Patients Using Conventional Biomarker Panel: A Prospective Study Protocol

by Saule Balmagambetova, Zhenisgul Tlegenova, Bekbolat Zholdin, Gulnara Kurmanalina, Iliada Talipova, Arip Koyshybaev, Dinara Nurmanova, Gulmira Sultanbekova, Mira Baspayeva, Saule Madinova, Kulparshan Kubenova and Ainel Urazova

Diagnostics 2022, 12(11), 2714; https://doi.org/10.3390/diagnostics12112714 - 06 Nov 2022

Cited by 7 | Viewed by 1723

Abstract

The prognosis of cancer treatment depends on, among other aspects, the cardiotoxicity of chemotherapy. This research aims to create a feasible algorithm for the early diagnosis of antitumor therapy cardiotoxicity in breast cancer patients. The paper represents a protocol for a prospective cohort [...] Read more.

The prognosis of cancer treatment depends on, among other aspects, the cardiotoxicity of chemotherapy. This research aims to create a feasible algorithm for the early diagnosis of antitumor therapy cardiotoxicity in breast cancer patients. The paper represents a protocol for a prospective cohort study with N 120 eligible participants admitted for treatment with anthracyclines and/or trastuzumab. These patients will be allocated into four risk groups regarding potential cardiotoxic complications. Patients will be examined five times every three months for six biomarkers: cardiac troponin I (cTnI), brain natriuretic peptide (BNP), C-reactive protein (CRP), myeloperoxidase (MPO), galectin-3 (Gal-3), and D-dimer, simultaneously with echocardiographic methods, including speckle tracking. The adjusted relative risk (aOR) of interrupting an entire course of chemotherapy due to cardiotoxic events will be assessed using multiple analyses of proportional Cox risks. The Cox model will also assess associations between baseline biomarker values and time to cardiotoxic events. Moreover, partly conditional survival models will be applied to determine associations between repeated assessments of changes in biomarkers from baseline and time to cancer therapy-related cardiac dysfunction. All models will be adjusted for cancer therapy regimen, baseline LVEF, groups at risk, baseline biomarker values, and age. The decision-tree and principal component analysis (PCA) methods will also be applied. Thus, feasible patterns will be detected. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers)

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