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: closed (5 April 2019).

Special Issue Editors

Prof. Dr. Liliana Rogozea
E-Mail Website
Guest Editor
Transilvania University of Brasov, Faculty of Medicine, Brasov, Romania
Interests: medicine; medical and health profession education; healthcare management; bioethics; history of science; telemedicine; rehabilitation
Special Issues and Collections in MDPI journals

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 semimonthly 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 2200 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 (22 papers)

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Editorial

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Editorial
Comment from the Editors on the Special Issue: Advanced Analytical Methods in Clinical Diagnosis and Therapy
J. Clin. Med. 2019, 8(11), 1936; https://doi.org/10.3390/jcm8111936 - 10 Nov 2019
Viewed by 552
Abstract
With this Editorial, we want to present the Special Issue, “Advanced Analytical Methods in Clinical Diagnosis and Therapy”. The development of medicine is not possible without progress in the field of identifying different biomarkers or treatments using modern approaches, such as the analytical [...] Read more.
With this Editorial, we want to present the Special Issue, “Advanced Analytical Methods in Clinical Diagnosis and Therapy”. The development of medicine is not possible without progress in the field of identifying different biomarkers or treatments using modern approaches, such as the analytical methods presented in articles that are part of this issue. Thus, with the support of experts, both aspects of theoretical and practical interest from different fields of pathologies have been addressed. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)

Research

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Article
γ-Glutamyltransferase Variability and the Risk of Mortality, Myocardial Infarction, and Stroke: A Nationwide Population-Based Cohort Study
J. Clin. Med. 2019, 8(6), 832; https://doi.org/10.3390/jcm8060832 - 12 Jun 2019
Cited by 5 | Viewed by 885
Abstract
Although it has been suggested that the γ-glutamyltransferase (GGT) level is an indicator of cardiometabolic disorders, there is no previous study to evaluate the implication of GGT variability on the development of myocardial infarction (MI), stroke, all-cause mortality, and cardiovascular disease (CVD)-related mortality. [...] Read more.
Although it has been suggested that the γ-glutamyltransferase (GGT) level is an indicator of cardiometabolic disorders, there is no previous study to evaluate the implication of GGT variability on the development of myocardial infarction (MI), stroke, all-cause mortality, and cardiovascular disease (CVD)-related mortality. GGT variability was measured as the coefficient variance (GGT-CV), standard deviation (GGT-SD), and variability independent of the mean (GGT-VIM). Using the population-based Korean National Health Insurance Service-Health Screening Cohort, we followed 158,736 Korean adults over a median duration of 8.4 years. In multivariable Cox proportional hazard analysis, the risk of mortality, MI, and stroke showed a stepwise increase according to the quartiles of GGT-CV, GGT-SD or GGT-VIM. In the highest quartile of GGT-CV compared to the lowest quartile after adjusting for confounding variables including mean GGT, the hazard ratios (HRs) for incident MI, stroke, mortality, and CVD-related mortality were 1.19 (95% confidence interval (CI), 1.06–1.34; p < 0.001), 1.20 (95% CI, 1.10–1.32; p < 0.001), 1.41 (95% CI, 1.33–1.51; p < 0.001), and 1.52 (95% CI, 1.30–1.78; p < 0.001), respectively, which were similar or even higher compared with those associated with total cholesterol variability. This is the first study to demonstrate that high GGT variability is associated with increased risk of MI, stroke, all-cause mortality, and CVD-related mortality in the general population. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Trends of Lipophilic, Antioxidant and Hematological Parameters Associated with Conventional and Electronic Smoking Habits in Middle-Age Romanians
J. Clin. Med. 2019, 8(5), 665; https://doi.org/10.3390/jcm8050665 - 12 May 2019
Cited by 3 | Viewed by 1205
Abstract
It is known that cigarette smoking is correlated with medical associated inquires. New electronic cigarettes are intensively advertised as an alternative to conventional smoking, but only a few studies demonstrate their harmful potential. A cross-sectional study was designed using 150 subjects from Brasov [...] Read more.
It is known that cigarette smoking is correlated with medical associated inquires. New electronic cigarettes are intensively advertised as an alternative to conventional smoking, but only a few studies demonstrate their harmful potential. A cross-sectional study was designed using 150 subjects from Brasov (Romania), divided into three groups: non-smokers (NS = 58), conventional cigarettes smokers (CS = 58) and electronic cigarettes users (ECS = 34). The aim of this study was to determine levels of some plasma lipophilic and hematological components, and the total antioxidant status that could be associated with the smoking status of the subjects. Serum low density lipoproteins (LDL) cholesterol increased significantly for ECS participants versus NS group (18.9% difference) (p < 0.05). Also, the CS group is characterized by an increase of serum LDL cholesterol (7.9% difference vs. NS), but with no significant statistical difference. The variation of median values of serum very low density lipoproteins (VLDL) was in order NS < ECS < CS, with statistical difference between NS and CS groups (34.6% difference; p = 0.023). When comparing the antioxidant status of the three groups, significant differences (p < 0.05) were obtained between NS vs. CS and NS vs. ECS. Similar behavior was identified for CS and ECS. Statistically significant changes (p < 0.0001) for both vitamin A and vitamin E were identified in the blood of NS vs. CS and NS vs. ECS, and also when comparing vitamin A in the blood of the CS group versus the ECS group (p < 0.05). When all groups were compared, the difference in the white blood cell (WBC) was (p = 0.008). A slight increase in the red blood cell (RBC) count was observed, but with no statistical difference between groups. These results indicated that conventional cigarette and e-cigarette usage promotes the production of excess reactive oxygen species, involving different pathways, different antioxidants and bioactive molecules. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
New Generation Cardiac Contractility Modulation Device—Filling the Gap in Heart Failure Treatment
J. Clin. Med. 2019, 8(5), 588; https://doi.org/10.3390/jcm8050588 - 29 Apr 2019
Cited by 6 | Viewed by 1921
Abstract
(1) Background: Heart failure (HF) is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high. Device therapy for HF mainly includes cardiac resynchronization therapy (CRT) and the use of an [...] Read more.
(1) Background: Heart failure (HF) is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high. Device therapy for HF mainly includes cardiac resynchronization therapy (CRT) and the use of an implantable cardioverter-defibrillator (ICD). Recently, however, a new device therapy—cardiac contractility modulation (CCM)—became available. (2) Aim: The purpose of this study is to present a first case-series of patients with different clinical patterns of HF with a reduced ejection fraction (HFrEF), supported with the newest generation of CCM devices. (3) Methods and results: Five patients with a left ventricular ejection fraction (LVEF) ≤ 35% and a New York Heart Association (NYHA) class ≥ III were supported with CCM OPTIMIZER® SMART IPGCCMX10 at our clinic. The patients had a median age of 67 ± 8.03 years (47–80) and were all males—four with ischemic etiology dilated cardiomyopathy. In two cases, CCM was added on top of CRT (non-responders), and, in one patient, CCM was delivered during persistent atrial fibrillation (AF). After 6 months of follow-up, the LVEF increased from 25.4 ± 6.8% to 27 ± 9%, and the six-minute walk distance increased from 310 ± 65.1 m to 466 ± 23.6 m. One patient died 47 days after device implantation. (4) Conclusion: CCM therapy provided with the new model OPTIMIZER® SMART IPG CCMX10 is safe, feasible, and applicable to a wide range of patients with HF. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Systemic Sclerosis Is Linked to Psoriasis and May Impact on Patients’ Survival: A Large Cohort Study
J. Clin. Med. 2019, 8(4), 521; https://doi.org/10.3390/jcm8040521 - 16 Apr 2019
Cited by 13 | Viewed by 1351
Abstract
Although skin manifestations are quite common in systemic sclerosis (SSc), a link between SSc and psoriasis (PsO) has been poorly investigated. We assessed the Clalit medical database in a cohort study to compare the prevalence of PsO between SSc-patients and SSc-free controls. We [...] Read more.
Although skin manifestations are quite common in systemic sclerosis (SSc), a link between SSc and psoriasis (PsO) has been poorly investigated. We assessed the Clalit medical database in a cohort study to compare the prevalence of PsO between SSc-patients and SSc-free controls. We also evaluated the SSc-related autoantibodies’ role in the co-existence of the two conditions. Survival analysis was performed using both univariate (Kaplan–Meier, log-rank test) and multivariate (Cox proportional-hazards technique) analyses. Our cohort of 2,431 SSc-patients was age- and gender-matched with 12,710 controls (case-control match 1:5.2). There were 150 (1.2%) cases of PsO among controls and 47 (1.9%) among SSc-patients (p = 0.0027). A SSc diagnosis was an independent risk factor for PsO with an odds ratio (OR) of 2.16 (95%CI 1.38–3.39, p = 0.0008). Among SSc-patients, 98.6% with PsO were antinuclear antibodies (ANA)-negative. In terms of survival, the mortality rate in SSc-patients with PsO was lower than SSc without PsO (14.9% vs. 26%, p < 0.0001). At the multivariate-analysis, SSc-patients with PsO compared to SSc-patients without PsO had an OR for death of 0.44 (95%CI 0.19–0.99, p < 0.05). SSc is independently associated with PsO. The cases with concurrent PsO and SSc are almost exclusively ANA-negative and may exhibit a better survival. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Adult Patient Risk Stratification Using a Risk Score for Periodontitis
by , and
J. Clin. Med. 2019, 8(3), 307; https://doi.org/10.3390/jcm8030307 - 05 Mar 2019
Cited by 2 | Viewed by 1516
Abstract
Background: There is a need for analytical tools predicting the risk of periodontitis. The purpose of this study was to estimate and evaluate a risk score for prediction of periodontitis. Materials and methods: This case-cohort study included a random sample of 155 cases [...] Read more.
Background: There is a need for analytical tools predicting the risk of periodontitis. The purpose of this study was to estimate and evaluate a risk score for prediction of periodontitis. Materials and methods: This case-cohort study included a random sample of 155 cases (with periodontitis) and 175 controls (randomly sampled from the study population at baseline) that were followed for 3-year. A logistic regression model was used with estimation of the risk ratio (RR) for each potential predictor. Results: The risk model included the predictors “age > 53 years” (RR = 0.53), “smoking” (RR = 2.9), “gingivitis at baseline” (RR = 3.1), “subgingival calculus at baseline” (RR = 1.9), “history of periodontitis” (RR = 2.3), and “less than 2 observations in the first year of follow-up” (RR = 3.7). Patients were distributed into three risk groups based on the preanalysis risk: low risk, moderate risk, and high risk. The risk score discrimination (95% confidence interval (CI)) was 0.75 (0.70; 0.80) (p < 0.001, C-statistic). Conclusions: The risk score estimated in the present study enabled to identify patients at higher risk of experiencing periodontitis and may be considered a useful tool for both clinicians and patients. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Impact of Long Non-Coding RNA HOTAIR Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma
J. Clin. Med. 2019, 8(3), 282; https://doi.org/10.3390/jcm8030282 - 26 Feb 2019
Cited by 11 | Viewed by 1274
Abstract
Increasing evidence shows that dysregulated expression of long non-coding (lnc)RNAs can serve as diagnostic or prognostic markers in urothelial cell carcinoma (UCC), the most common pathological type of bladder cancer. lncRNA HOX transcript antisense RNA (HOTAIR) was shown to promote tumor [...] Read more.
Increasing evidence shows that dysregulated expression of long non-coding (lnc)RNAs can serve as diagnostic or prognostic markers in urothelial cell carcinoma (UCC), the most common pathological type of bladder cancer. lncRNA HOX transcript antisense RNA (HOTAIR) was shown to promote tumor progression and be associated with a poor prognosis in multiple cancers including bladder cancer. Polymorphisms of HOTAIR were recently linked to a predisposition for diverse malignancies. Herein we conducted a case-control study to evaluate whether genetic polymorphisms of HOTAIR were associated with UCC risk and clinicopathologic characteristics. Four loci (rs920778 T>C, rs1899663 G>T, rs4759314 A>G, and rs12427129, C>T) of HOTAIR were genotyped by a TaqMan allelic discrimination method in 431 cases and 862 controls. We found that female patients who carried AG + GG genotype of rs4759314 were associated with an increased UCC risk after controlling for age and tobacco consumption (adjusted odds ratio (AOR) = 1.92, 95% confidence interval (CI): 1.01–3.64, p = 0.047) and a lower overall survival rate (p = 0.008). Moreover, patients with a smoking habit or younger age (≤65 years), who had at least one T allele of HOTAIR rs12427129 were at a higher risk of developing advance tumor T satge (p = 0.046), compared to those patients with CC homozygotes. In contrast, rs920778 C allele carriers were negatively correlated with the development of lymph node metastasis (OR = 0.51, 95% CI: 0.28–0.94, p = 0.031). Further analyses of clinical datasets revealed correlations of the expression of HOTAIR with tumor metastasis and a poor survival rate in patients with UCC. Our results verified the diverse impacts of HOTAIR variants on UCC susceptibility and clinicopathologic characteristics. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Spirit-Quieting Traditional Chinese Medicine May Improve Survival in Prostate Cancer Patients with Depression
J. Clin. Med. 2019, 8(2), 218; https://doi.org/10.3390/jcm8020218 - 08 Feb 2019
Cited by 5 | Viewed by 1711
Abstract
Depression is associated with higher mortality in prostate cancer. However, whether traditional Chinese medicine (TCM) for depression improves outcomes in patients with prostate cancer is unclear. This retrospective cohort study evaluated the association between TCM for depression and mortality in patients with prostate [...] Read more.
Depression is associated with higher mortality in prostate cancer. However, whether traditional Chinese medicine (TCM) for depression improves outcomes in patients with prostate cancer is unclear. This retrospective cohort study evaluated the association between TCM for depression and mortality in patients with prostate cancer. During the period 1998–2012, a total of 248 prostate cancer patients in Taiwan with depression were enrolled and divided into three groups: TCM for depression (n = 81, 32.7%), TCM for other purposes (n = 53, 21.3%), and no TCM (n = 114, 46.0%). During a median follow-up of 6.2 years, 12 (14.8%), 13 (24.5%), and 36 (31.6%) deaths occurred in the TCM for depression, TCM for other purposes, and no TCM groups, respectively. After adjusting age at diagnosis, urbanization, insured amount, comorbidity disease, and prostate cancer type, TCM for depression was associated with a significantly lower risk of overall mortality based on a multivariate-adjusted Cox proportional-hazards model (hazard ratio 0.42, 95% confidence interval: 0.21–0.85, p = 0.02) and Kaplan–Meier survival curve (log-rank test, p = 0.0055) compared to no TCM. In conclusion, TCM for depression may have a positive association with the survival of prostate cancer patients with depression. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Risk Score to Predict Dental Caries in Adult Patients for Use in the Clinical Setting
J. Clin. Med. 2019, 8(2), 203; https://doi.org/10.3390/jcm8020203 - 07 Feb 2019
Cited by 3 | Viewed by 1162
Abstract
Background: There is a need for risk prediction tools in caries research. This investigation aimed to estimate and evaluate a risk score for prediction of dental caries. Materials and Methods: This case-cohort study included a random sample of 177 cases (with dental caries) [...] Read more.
Background: There is a need for risk prediction tools in caries research. This investigation aimed to estimate and evaluate a risk score for prediction of dental caries. Materials and Methods: This case-cohort study included a random sample of 177 cases (with dental caries) and 220 controls (randomly sampled from the study population at baseline), followed for 3 years. The risk ratio (RR) for each potential predictor was estimated using a logistic regression model. The level of significance was 5%. Results: The risk model for dental caries included the predictors: “presence of bacterial plaque/calculus” (RR = 4.1), “restorations with more than 5 years” (RR = 2.3), “>8 teeth restored” (RR = 2.0), “history/active periodontitis” (RR = 1.7) and “presence of systemic condition” (RR = 1.4). The risk model discrimination (95% confidence interval) was 0.78 (0.73; 0.82) (p < 0.001, C-statistic). Patients were distributed into three risk groups based on the pre-analysis risk (54%): low risk (<half the pre-analysis risk; caries incidence = 6.8%), moderate risk (half-to-less than the pre-analysis risk; caries incidence = 20.4%) and high risk (≥the pre-analysis risk; caries incidence = 27%). Conclusions: The present study estimated a simple risk score for prediction of dental caries retrieved from a risk algorithm with good discrimination. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Predictive Factors for Platelet Count Variation After Splenectomy in Non-Traumatic Diseases
J. Clin. Med. 2019, 8(1), 82; https://doi.org/10.3390/jcm8010082 - 12 Jan 2019
Cited by 3 | Viewed by 1358
Abstract
Background: The spleen plays a central role in a range of diseases. As such, great emphasis has been placed on the procedure of spleen removal, the benefits and the numerous associated complications. Given the immediate risk of the thrombotic complications, the aim of [...] Read more.
Background: The spleen plays a central role in a range of diseases. As such, great emphasis has been placed on the procedure of spleen removal, the benefits and the numerous associated complications. Given the immediate risk of the thrombotic complications, the aim of this study was to evaluate clinical and laboratory patient characteristics in non-traumatic diseases of the spleen, and to investigate possible predictive factors for platelet count variation following the procedure. Methods: A total of 72 patients who underwent splenectomy were included in this retrospective study. Correlation coefficients as well as multiple linear regressions were used to assess the relationship between post-splenectomy platelet count and various preoperative clinical and laboratory patient characteristics. Results: Following multiple linear regression analysis, we determined that 54.93% of post-splenectomy platelet count variation was explained by admission platelet count (p = 0.00), lymphocyte count (p = 0.04), WBC count (p = 0.00), LOS (p = 0.00), patient gender (p = 0.00), spleen accessibility on admission (p = 0.02) and PT (p = 0.00). Conclusions: Platelet count variation following splenectomy for non-traumatic diseases can be predicted by assessing preoperative patient characteristics. The implications of this study suggest that by means of a prediction model, patient care could benefit from assessing and addressing various preoperative factors that lead to these complications. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
Non-Invasive Assessment Method Using Thoracic-Abdominal Profile Image Acquisition and Mathematical Modeling with Bezier Curves
J. Clin. Med. 2019, 8(1), 65; https://doi.org/10.3390/jcm8010065 - 09 Jan 2019
Cited by 3 | Viewed by 1294
Abstract
The study was performed at Brasov County Hospital, in the Internal Medicine, Diabetes, Gastroenterology and Cardiology Wards with the collaboration of Transylvania University of Brasov, as a study approved by the Ethical Board of the university. The study aimed at assessing the connection [...] Read more.
The study was performed at Brasov County Hospital, in the Internal Medicine, Diabetes, Gastroenterology and Cardiology Wards with the collaboration of Transylvania University of Brasov, as a study approved by the Ethical Board of the university. The study aimed at assessing the connection between the anthropometric parameters of abdominal adiposity (measured by means of an original experiment designed to determine the curvature of the thoracic-abdominal adiposity for the patients and processed by help of a mathematical model based upon Bezier curves geometry) and the fat load of the liver (assessed by ultrasound by measuring the diameters of both hepatic lobes) for the patients diagnosed with Non-Alcoholic Fatty Liver Disease (NAFLD). The existence of ten types of thoracic-abdominal curves profiles were statistically analyzed in order to evaluate in a simple manner the liver size in NAFLD. The method of diagnosis is based on an easily reproduced experiment, it is original, innovative, non-invasive, and cost-effective. Can be implemented anywhere in the world, there is no need for investment, only for determining the profile of the belly. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
CRT Pacing: Midterm Follow-Up in LV Only Pacing without RV Lead in Patients with Normal AV Conduction
J. Clin. Med. 2018, 7(12), 531; https://doi.org/10.3390/jcm7120531 - 08 Dec 2018
Cited by 3 | Viewed by 1491
Abstract
Background: The aim of our study was to assess the real life cardiac resynchronization therapy (CRT) fusion left ventricular (LV) only pacing in patients with normal AV conduction (NAVc) without right ventricular (RV) lead. Methods: Consecutive NAVc patients with CRT indication were implanted [...] Read more.
Background: The aim of our study was to assess the real life cardiac resynchronization therapy (CRT) fusion left ventricular (LV) only pacing in patients with normal AV conduction (NAVc) without right ventricular (RV) lead. Methods: Consecutive NAVc patients with CRT indication were implanted with a right atrium RA/LV DDD pacing system. Complete follow-up at 1, 3 and every 6 months thereafter included echocardiography and stress testing. Results: We analysed 55 patients (62 ± 11 years). All patients were responders with significant LV reverse remodelling (LV end-diastolic volume 193.7 ± 81 vs. 243.2 ± 82 mL at baseline, p < 0.002) and increased LV ejection fraction (38 ± 7.9% vs. 27 ± 5.2% at baseline, p < 0.001). Mitral regurgitation decreased in 38 patients (69%). During follow-up (35 ± 18 months), 20 patients (36%) needed reprogramming sensed/paced AV delay or maximum tracking rate (MTR) because of inadequate or lost LV capture at exercise test; personalized programming to achieve up to 100% fusion pacing was used in all patients. One patient developed Mobitz II second degree AV block and triple chamber CRT-P upgrade was performed; defibrillator upgrade was not necessary. Conclusions: LV only pacing CRT-P without RV lead showed a positive outcome in carefully selected patients. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Article
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 - 10 Nov 2018
Cited by 1 | Viewed by 1603
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 [...] Read more.
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)
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Article
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 - 08 Nov 2018
Cited by 10 | Viewed by 1466
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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Article
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 - 07 Nov 2018
Cited by 18 | Viewed by 1940
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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Article
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 - 16 Oct 2018
Cited by 4 | Viewed by 1417
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 [...] Read more.
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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Article
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 - 08 Oct 2018
Cited by 32 | Viewed by 1809
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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Article
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 - 04 Oct 2018
Cited by 8 | Viewed by 1319
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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Article
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 - 11 Sep 2018
Cited by 10 | Viewed by 1549
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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Article
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 - 04 Sep 2018
Cited by 1 | Viewed by 1399
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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Review

Jump to: Editorial, Research

Review
Circulating miRNAs as Biomarkers for Endometriosis and Endometriosis-Related Ovarian Cancer—An Overview
J. Clin. Med. 2019, 8(5), 735; https://doi.org/10.3390/jcm8050735 - 23 May 2019
Cited by 11 | Viewed by 2333
Abstract
Early detection and accurate diagnosis are pivotal in the management of endometriosis and endometriosis-related ovarian neoplasms (ERONs), yet there is no clear common ground regarding their pathogenesis. Endometriosis is a debilitating pathology that profoundly impairs the quality of life. Although the spontaneous resolution [...] Read more.
Early detection and accurate diagnosis are pivotal in the management of endometriosis and endometriosis-related ovarian neoplasms (ERONs), yet there is no clear common ground regarding their pathogenesis. Endometriosis is a debilitating pathology that profoundly impairs the quality of life. Although the spontaneous resolution of endometriosis is possible, studies suggest that it can be a progressive condition, and ERONs can develop. The gold standard for diagnosis remains as the invasive method of laparoscopy followed by histological confirmation. In recent years, novel biomarkers have been discovered. MicroRNAs (miRNA) represent important epigenetic modulators of gene expression and are very attractive as biomarkers due to their lower complexity, tissue specificity, and stability in bodily fluids. Several studies have advanced the possibility of miRNAs becoming potential biomarkers in endometriosis and ERONs. Our aim is to bring these studies together in order to have a better understanding of whether, how, and when miRNAs might be used as biomarkers for these pathologies. Methods: We selected the reviewed papers from Google Academic, PubMed, and CrossRef. A total of eight studies met the inclusion criteria. Results: MiR-200 family, miR-143, 145, miR-20a, and miR199a were the most commonly dysregulated miRNAs in endometriosis, and miR-200 family was found to be dysregulated in both ERONs and endometriosis. Conclusions: No single miRNA was considered as a sole biomarker for this pathology. However, since the prognostic value of biomarkers is generally enhanced if more are assessed at the same time, a panel of miRNAs could be a better indicator of the disease. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Review
Recent Trends in the Quantification of Biogenic Amines in Biofluids as Biomarkers of Various Disorders: A Review
J. Clin. Med. 2019, 8(5), 640; https://doi.org/10.3390/jcm8050640 - 09 May 2019
Cited by 8 | Viewed by 1474
Abstract
Biogenic amines (BAs) are bioactive endogenous compounds which play a significant physiological role in many cell processes like cell proliferation and differentiation, signal transduction and membrane stability. Likewise, they are important in the regulation of body temperature, the increase/decrease of blood pressure or [...] Read more.
Biogenic amines (BAs) are bioactive endogenous compounds which play a significant physiological role in many cell processes like cell proliferation and differentiation, signal transduction and membrane stability. Likewise, they are important in the regulation of body temperature, the increase/decrease of blood pressure or intake of nutrition, as well as in the synthesis of nucleic acids and proteins, hormones and alkaloids. Additionally, it was confirmed that these compounds can be considered as useful biomarkers for the diagnosis, therapy and prognosis of several neuroendocrine and cardiovascular disorders, including neuroendocrine tumours (NET), schizophrenia and Parkinson’s Disease. Due to the fact that BAs are chemically unstable, light-sensitive and possess a high tendency for spontaneous oxidation and decomposition at high pH values, their determination is a real challenge. Moreover, their concentrations in biological matrices are extremely low. These issues make the measurement of BA levels in biological matrices problematic and the application of reliable bioanalytical methods for the extraction and determination of these molecules is needed. This article presents an overview of the most recent trends in the quantification of BAs in human samples with a special focus on liquid chromatography (LC), gas chromatography (GC) and capillary electrophoresis (CE) techniques. Thus, new approaches and technical possibilities applied in these methodologies for the assessment of BA profiles in human samples and the priorities for future research are reported and critically discussed. Moreover, the most important applications of LC, GC and CE in pharmacology, psychology, oncology and clinical endocrinology in the area of the analysis of BAs for the diagnosis, follow-up and monitoring of the therapy of various health disorders are presented and critically evaluated. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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