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Special Issue "Advanced Analytical Methods in Clinical Diagnosis and Therapy"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Epidemiology & Public Health".

Deadline for manuscript submissions: 5 April 2019

Special Issue Editors

Guest Editor
Prof. Dr. Monica Florescu

Transilvania University of Brasov, Faculty of Medicine, Brasov, Romania
Website | E-Mail
Interests: biophysics; electrochemical and optical nanosensors/nanobiosensors for medical applications; biomolecular interactions
Guest Editor
Prof. Dr. Liliana Rogozea

Transilvania University of Brasov, Faculty of Medicine, Brasov, Romania
Website | E-Mail
Interests: medicine; medical & health profession education; health care management; bioethics; history of science; telemedicine; rehabilitation

Special Issue Information

Dear Colleagues,

The use of biomarkers is more and more common for various purposes, e.g., detection, monitoring and treatment of the molecular causes of diseases; molecular markers and genetic variations that affect drug response, development of new drugs, adverse effects and/or disease progression; new tools and technologies for diagnosis and therapy; and ethical and regulatory issues related to personalized medicine. In this Special Issue, we invite manuscripts dealing with advances in health care/clinical practices, the study of direct observation of patients and general medical research, while not being limited to those, which will be or not presented in the frame of the IC-ANMBES 2018 (https://sciforum.net/conference/icanmbes2018). Both original research and review articles are welcomed.

Original research papers that describe the development, characterization/evaluation, simulations and utilization of different advanced analytical methods in clinical diagnosis and therapy and the reviews should provide an up-to-date and critical overview of state-of-the-art of those methods. The subject areas are shown at https://www.mdpi.com/journal/jcm/about.

Please feel free to contact us and send us your suggestions that you would like to discuss beforehand. We look forward to and welcome your participation in this Special Issue.

Prof. Dr. Monica Florescu
Prof. Dr. Liliana Rogozea
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 papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue 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. Journal of Clinical Medicine 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 1000 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

  • Analytical methods
  • Diagnosis
  • Therapy
  • Clinical laboratory
  • Medical imaging
  • Telemedicine
  • Rehabilitation medicine

Published Papers (8 papers)

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Research

Open AccessArticle Diagnostic Performance of Initial Serum Albumin Level for Predicting In-Hospital Mortality among Necrotizing Fasciitis Patients
J. Clin. Med. 2018, 7(11), 435; https://doi.org/10.3390/jcm7110435
Received: 16 October 2018 / Revised: 4 November 2018 / Accepted: 8 November 2018 / Published: 10 November 2018
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Abstract
Background: Hypoalbuminemia is known to be associated with adverse outcomes in critical illness. In this study, we attempted to identify whether hypoalbuminemia on emergency department (ED) arrival is a reliable predictor for in-hospital mortality in necrotizing fasciitis (NF). patients. Method: A retrospective cohort
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Background: Hypoalbuminemia is known to be associated with adverse outcomes in critical illness. In this study, we attempted to identify whether hypoalbuminemia on emergency department (ED) arrival is a reliable predictor for in-hospital mortality in necrotizing fasciitis (NF). patients. Method: A retrospective cohort study of hospitalized adult patients with NF was conducted in a tertiary teaching hospital in Taiwan between March 2010 and March 2018. Blood samples were collected in the ED upon arrival, and serum albumin levels were determined. We evaluated the predictive value of serum albumin level at ED presentation for in-hospital mortality. All collected data were statistically analyzed. Result: Of the 707 NF patients, 40 (5.66%) died in the hospital. The mean serum albumin level was 3.1 ± 0.9 g/dL and serum albumin levels were significantly lower in the non-survivor group than in the survivor group (2.8 ± 0.7 g/dL vs. 3.5 ± 0.8 g/dL). In the multivariable logistic regression model, albumin was significantly associated with in-hospital mortality (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.88–0.96, p < 0.001). The area under-the-receiver-operating-characteristic curve (AUC) for in-hospital survival was 0.77 (95% CI 0.72–0.82) and corresponding sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were 66%, 74%, 33%, 88%, 2.25, and 0.48, respectively. High sensitivity (96%) for survival was shown at albumin level of 4.0 g/dL and high specificity (91%) for mortality was shown at a level of 2.5 g/dL. Conclusion: Initial serum albumin levels strongly predicted in-hospital mortality among patients with necrotizing fasciitis. NF patients with hypoalbuminemia on ED arrival should be closely monitored for signs of deterioration and early and aggressive intervention should be considered to prevent mortality. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
Open AccessArticle Combination of Plasma Biomarkers and Clinical Data for the Detection of Myocardial Fibrosis or Aggravation of Heart Failure Symptoms in Heart Failure with Preserved Ejection Fraction Patients
J. Clin. Med. 2018, 7(11), 427; https://doi.org/10.3390/jcm7110427
Received: 13 September 2018 / Revised: 3 November 2018 / Accepted: 5 November 2018 / Published: 8 November 2018
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Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms and structural change (including fibrosis). The relationship between novel biomarkers and the above components remains unclear. Methods: Seventy-seven HFpEF patients were recruited. All patients underwent echocardiography with tissue doppler
[...] Read more.
Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms and structural change (including fibrosis). The relationship between novel biomarkers and the above components remains unclear. Methods: Seventy-seven HFpEF patients were recruited. All patients underwent echocardiography with tissue doppler imaging, cardiac magnetic resonance imaging (CMRI), and measurement of plasma inflammatory, remodelling, endothelial function, and heart failure biomarker levels. Myocardial fibrosis was defined by CMRI-extracellular volume. Forward conditional logistic regression was applied to demonstrate the determinants of myocardial fibrosis or heart failure symptoms. Results: The levels of growth differentiation factor, tissue inhibitor of metalloproteinase (TIMP)-1, galectin-3, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were significantly higher in patients with more myocardial fibrosis. Matrix metalloproteinase-2 (MMP-2) and galectin-3 were independent markers of ECV. After adjusting for confounding factors, plasma galectin-3 and MMP-2 levels were correlated with myocardial fibrosis levels (odds ratio (OR): 1.05, 95% confidence interval (CI): 1.02 to 1.09, p = 0.005 and OR: 2.11, 95% CI: 1.35–3.28, respectively), while NT-proBNP level only was associated with heart failure symptoms. We developed a score system consisted of biomarkers and clinical parameters. The area under the curve of the scoring system receiver operating characteristic curve is 0.838 to predict the degree of myocardial diffuse fibrosis. Conclusions: In conclusion, we found that galectin-3 and MMP-2 were significantly associated with global cardiac fibrosis in HFpEF patients. We also combined plasma biomarkers and clinical data to identify HFpEF patients with more severe cardiac fibrosis. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA
J. Clin. Med. 2018, 7(11), 420; https://doi.org/10.3390/jcm7110420
Received: 24 September 2018 / Revised: 30 October 2018 / Accepted: 4 November 2018 / Published: 7 November 2018
PDF Full-text (705 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1,
[...] Read more.
Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1, PSAT1, RASSF1A and SCGB3A1). Methods: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes’ methylation levels. Results: The gene-panel APC, FOXA1, RASSF1A, SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1-methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1-methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA (APC, FOXA1 and RASSF1A) disclosed a sensitivity, specificity and accuracy over 70%. Conclusions: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus
J. Clin. Med. 2018, 7(10), 360; https://doi.org/10.3390/jcm7100360
Received: 26 August 2018 / Revised: 11 October 2018 / Accepted: 13 October 2018 / Published: 16 October 2018
PDF Full-text (1185 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening
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Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening ARR in PA patients with diabetes. The study enrolled consecutive patients and they underwent ARR testing at screening. Then the diagnosis of PA was confirmed from the Taiwan Primary Aldosteronism Investigation registration dataset. Generalized additive model smoothing plot was used to validate the performance of screening ARR in PA patients with or without diabetes. During this study period, 844 PA patients were confirmed and 136 (16.0%) among them had diabetes. Other 816 patients were diagnosed with essential hypertension and used as the control group and 89 (10.9%) among them had diabetes. PA patients with diabetes were older and had a longer duration of hypertensive latency, higher systolic blood pressure and lower glomerular filtration rate than those PA patients without diabetes. The cut-off value of ARR in the generalized additive model predicting PA was 65 ng/dL per ng/mL/h in diabetic patients, while 45 ng/dL per ng/mL/h in non-diabetic patients. There was a considerable prevalence of diabetes among PA patients, which might be capable of interfering with the conventional screening test. The best cut-off value of ARR, more than 65 ng/dL per ng/mL/h in PA patients with diabetes, was higher than those without diabetes. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Critically Ill Patients
J. Clin. Med. 2018, 7(10), 333; https://doi.org/10.3390/jcm7100333
Received: 24 August 2018 / Revised: 28 September 2018 / Accepted: 4 October 2018 / Published: 8 October 2018
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Abstract
The C-reactive protein (CRP)/albumin ratio has recently emerged as a marker for poor prognosis or mortality across various patient groups. This study aimed to identify the association between CRP/albumin ratio and 28-day mortality and predict the accuracy of CRP/albumin ratio for 28-day mortality
[...] Read more.
The C-reactive protein (CRP)/albumin ratio has recently emerged as a marker for poor prognosis or mortality across various patient groups. This study aimed to identify the association between CRP/albumin ratio and 28-day mortality and predict the accuracy of CRP/albumin ratio for 28-day mortality in medical intensive care unit (ICU) patients. This was a retrospective cohort study of 875 patients. We evaluated the prognostic value of CRP/albumin ratio to predict mortality at 28 days after ICU admission, using Cox proportional hazard model and Kaplan-Meier survival analysis. The 28-day mortality was 28.0%. In the univariate analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p < 0.001), CRP level (p = 0.045), albumin level (p < 0.001), and CRP/albumin ratio (p = 0.032) were related to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (the area under the ROC curves (AUC)) of CRP/albumin ratio was higher than that of CRP for mortality (0.594 vs. 0.567, p < 0.001). The cut-off point for CRP/albumin ratio for mortality was 34.3. On Cox proportional-hazard regression analysis, APACHE II score (hazards ratio (HR) = 1.05, 95% confidence interval (CI) = 1.04–1.07, p < 0.001) and CRP/albumin ratio (HR = 1.68, 95% CI = 1.27–2.21, p < 0.001 for high CRP/albumin ratio) were independent predictors of 28-day mortality. Higher CRP/albumin ratio was associated with increased mortality in critically ill patients. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle The Effect of Statin Added to Systemic Anticancer Therapy: A Meta-Analysis of Randomized, Controlled Trials
J. Clin. Med. 2018, 7(10), 325; https://doi.org/10.3390/jcm7100325
Received: 30 August 2018 / Revised: 25 September 2018 / Accepted: 2 October 2018 / Published: 4 October 2018
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Abstract
Preclinical studies have demonstrated that statins have anticancer properties and act in an additive or synergistic way when combined with anticancer therapy. We conducted this meta-analysis of randomized, controlled phase II or III trials to evaluate the effect of statins added to systemic
[...] Read more.
Preclinical studies have demonstrated that statins have anticancer properties and act in an additive or synergistic way when combined with anticancer therapy. We conducted this meta-analysis of randomized, controlled phase II or III trials to evaluate the effect of statins added to systemic anticancer therapy in patients with solid cancer. A systematic literature search was performed to identify all randomized trials that were designed to investigate the effect of statins in patients with cancer using PubMed, EMBASE, Google Scholar, and Web of Science (up to August 2018). From eight randomized controlled trials, 1760 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for grade 3–5 adverse events (AEs) and overall response rate (ORR) and hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). The addition of statin to anticancer agents did not significantly increase the incidence of grade 3–5 AEs (OR = 1.03, 95% CI: 0.81–1.29, p = 0.78). However, the combination of statin and anticancer agents did not improve ORR (OR = 0.96, 95% CI: 0.77–1.20, p = 0.72) compared with that of anticancer therapy alone. In addition, statins added to systemic anticancer therapy failed to prolong PFS (HR = 0.99, 95% CI: 0.90–1.10, p = 0.92) and OS (HR = 0.91, 95% CI: 0.76–1.11, p = 0.52). In conclusion, this meta-analysis of randomized controlled trials does not support clinical benefits of statins added to systemic anticancer therapy in patients with solid cancer. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection
J. Clin. Med. 2018, 7(9), 267; https://doi.org/10.3390/jcm7090267
Received: 15 August 2018 / Revised: 7 September 2018 / Accepted: 9 September 2018 / Published: 11 September 2018
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Abstract
Background: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive
[...] Read more.
Background: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4 index, and AST to platelet ratio index (APRI) based on histopathological analysis of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV) infection. Methods: Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores were calculated using preserved serum samples. The fibrosis staging and activity grading were assessed using a modified METAVIR score. Results: A total of 122 patients were enrolled; the cohort included 27 patients with stage 1, 66 with stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four fibrosis biomarkers presented AUC values greater than 0.8. Each of the four biomarkers in stage 2 was significantly different between the activity grade 1 and 2 groups. Conclusion: Fib-4 index and APRI were comparable with WFA-M2BP and ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with HCV infection. All four biomarkers of liver fibrosis were influenced by histopathological activity grading, which implies that liver biopsy should be the gold standard to evaluate liver fibrosis staging even though several noninvasive biomarkers have been investigated well. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle Clinical Outcome and Management for Geriatric Traumatic Injury: Analysis of 2688 Cases in the Emergency Department of a Teaching Hospital in Taiwan
J. Clin. Med. 2018, 7(9), 255; https://doi.org/10.3390/jcm7090255
Received: 23 July 2018 / Revised: 23 August 2018 / Accepted: 3 September 2018 / Published: 4 September 2018
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Abstract
Geriatric traumatic injuries in emergency departments are frequent and associated with higher mortality rates and catastrophic functional outcomes. Several prediction scores have been established to manage traumatic patients, including the shock index (SI), revised trauma score (RTS), injury severity score (ISS), trauma injury
[...] Read more.
Geriatric traumatic injuries in emergency departments are frequent and associated with higher mortality rates and catastrophic functional outcomes. Several prediction scores have been established to manage traumatic patients, including the shock index (SI), revised trauma score (RTS), injury severity score (ISS), trauma injury severity score (TRISS), and new injury severity score (NISS). However, it was necessary to investigate the effectiveness and efficiency of care for the geriatric traumatic population. In addition, image studies such as computed tomography and magnetic resonance imaging play an important role in early diagnosis and timely intervention. However, few studies focus on this aspect. The association between the benefit of carrying out more image studies and clinical outcomes remains unclear. In this study, we included a total of 2688 traumatic patients and analyzed the clinical outcomes and predicting factors in terms of geriatric trauma via pre-hospital and in-hospital analysis. Our evaluation revealed that a shock index ≥1 may be not a strong predictor of geriatric trauma due to the poor physical response in the aging population. This should be modified in geriatric patients. Other systems, like RTS, ISS, TRISS, and NISS, were significant in terms of predicting the clinical outcome. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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