ISSN / EISSN : 2075-4418 / 2075-4418
Current Publisher: MDPI (10.3390)
Total articles ≅ 1,368
Latest articles in this journal
Diagnostics, Volume 10; doi:10.3390/diagnostics10110870
To evaluate contrast-enhanced dual-energy computed tomography (DECT) chest examinations regarding pulmonary perfusion patterns and pulmonary opacities in patients with confirmed COVID-19 disease. Fourteen patients with 24 DECT examinations performed between April and May 2020 were included in this retrospective study. DECT studies were assessed independently by two radiologists regarding pulmonary perfusion defects, using a Likert scale ranging from 1 to 4. Furthermore, in all imaging studies the extent of pulmonary opacities was quantified using the same rating system as for perfusion defects. The main pulmonary findings were ground glass opacities (GGO) in all 24 examinations and pulmonary consolidations in 22 examinations. The total lung scores after the addition of the scores of the single lobes showed significantly higher values of opacities compared to perfusion defects, with a median of 12 (9–18) for perfusion defects and a median of 17 (15–19) for pulmonary opacities (p = 0.002). Furthermore, mosaic perfusion patterns were found in 19 examinations in areas with and without GGO. Further studies will be necessary to investigate the pathophysiological background of GGO with maintained perfusion compared to GGO with reduced perfusion, especially regarding long-term lung damage and prognosis.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110871
Acetylsalicylic acid (ASA), also known as aspirin, appears to be ineffective in inhibiting platelet aggregation in 20–30% of patients. Light transmission aggregometry (LTA) is a gold standard platelet function assay. In this pilot study, we used LTA to personalize ASA therapy ex vivo in atherosclerotic patients. Patients were recruited who were on 81 mg ASA, presenting to ambulatory clinics at St. Michael’s Hospital (n = 64), with evidence of atherosclerotic disease defined as clinical symptoms and diagnostic findings indicative of symptomatic peripheral arterial disease (PAD), with an ankle brachial index (ABI) of n = 52) or had diagnostic features of asymptomatic carotid arterial stenosis (CAS), with >50% stenosis of internal carotid artery on duplex ultrasound (n = 12). ASA compliance was assessed via multisegmented injection-capillary electrophoresis-mass spectrometry based on measuring the predominant urinary ASA metabolite, salicyluric acid. LTA with arachidonic acid was used to test for ASA sensitivity. Escalating ASA dosages of 162 mg and 325 mg were investigated ex vivo for ASA dose personalization. Of the 64 atherosclerotic patients recruited, 8 patients (13%) were non-compliant with ASA. Of ASA compliant patients (n = 56), 9 patients (14%) were non-sensitive to their 81 mg ASA dosage. Personalizing ASA therapy in 81 mg ASA non-sensitive patients with escalating dosages of ASA demonstrated that 6 patients became sensitive to a dosage equivalent to 162 mg ASA and 3 patients became sensitive to a dosage equivalent to 325 mg ASA. We were able to personalize ASA dosage ex vivo in all ASA non-sensitive patients with escalating dosages of ASA within 1 h of testing.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110872
Establishing the Kirsten rat sarcoma (KRAS) mutational status is essential in terms of managing patients with various types of cancer. Allele-specific real-time polymerase chain reaction (AS-PCR) is a widely used method for somatic mutations detection. To improve the limited sensitivity and specificity, several blocking methods have been introduced in AS-PCR to block the amplification of wild-type templates. Herein, we used a novel modified oligonucleotide with internucleotide phosphates reshaped 1,3-dimethyl-2-imino-imidazolidine moieties (phosphoryl guanidine (PG) groups) as primers and blockers in the AS-PCR method. Four common KRAS mutations were chosen as a model to demonstrate the advantages of the PG primers and blockers utilizing a customized PCR protocol. The methods were evaluated on plasmid model systems providing a KRAS mutation detection limit of 20 copies of mutant DNA in a proportion as low as 0.1% of the total DNA, with excellent specificity. PG-modification can serve as the universal additional mismatch-like disturbance to increase the discrimination between wild-type and mutated DNA. Moreover, PG can serve to increase primer specificity by a synergetic effect with additional mismatch and would greatly facilitate medical research.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110869
Pancreatic cancer (PC) is one of the most aggressive forms of cancer. Negative prognosis is mainly due to the late diagnosis in advanced stages, when the disease is already therapeutically overcome. Studies in recent years have focused on identifying biomarkers that could play a role in early diagnosis, leading to the improvement of morbidity and mortality. Currently, the only biomarker widely used in the diagnosis of PC is carbohydrate antigen 19-9 (CA19.9), which has, however, more of a prognostic role in the follow-up of postoperative recurrence than a diagnostic role. Other biomarkers, recently identified as the methylation status of ADAMTS1 (A disintegrin and metalloproteinase with thrombospondin motifs 1) and BNC1 (zinc finger protein basonuclin-1) in cell-free deoxyribonucleic acid (DNA), may play a role in the early detection of PC. This review focuses on the diagnosis of PC in its early stages.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110865
Luminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time PCR the gene expression of 19 factors implicated in tumor progression. Those factors included the calcium-binding protein S100A4, several growth factors (FGF2, FGF7, HGF, PDGFA, PDGFB, TGFβ, VEGFA, and IGF2), and we also studied inflammatory cytokines (IL6 and IL8), chemokines (CCL2, CXCL12), important proteases (uPA, MMP2, MMP9 and MMP11), the nuclear factor NFκB, and the metalloprotease inhibitor TIMP1, from luminal A and luminal B breast carcinoma CAFs. We performed a similar analysis after co-culturing CAFs with MCF-7 and MDA-MB-231 breast cancer cell lines. MMP-9 and CCL2 gene expressions were higher in CAFs from luminal B tumors. We also found different patterns in the induction of pro-tumoral factors from different CAFs populations co-cultured with different cancer cell lines. Globally, CAFs from luminal B tumors showed a higher expression of pro-tumor factors compared to CAFs from luminal A tumors when co-cultured with breast cancer cell lines. Moreover, we found that CAFs from metastatic tumors had higher IGF-2 gene expression, and we detected the same after co-culture with cell lines. Our results show the variability in the capacities of CAFs from luminal breast carcinomas, which may contribute to a better biological and clinical characterization of these cancer subtypes.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110867
Heart rate monitors (HRMs) are important for measuring heart rate, which can be used as a training parameter for healthy athletes. They indicate stress-related heart rhythm disturbances—recognized as an unexpected increase in heart rate (HR)—which can be life-threatening. Most HRMs confuse arrhythmias with artifacts. This study aimed to assess the usefulness of electrocardiogram (ECG) recordings from sport HRMs for endurance athletes, coaches, and physicians, compared with other basic and hypothetical functions. We conducted three surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), 10 coaches, and 10 sports doctors to obtain information on how important ECG recordings are and what HRM functions should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as their preference for HRM type (optical/strap). Athletes reported distance, pace, instant HR, and oxygen threshold as being the four most important functions. ECG recording ranked eighth and ninth for momentary and continuous recording, respectively. Coaches placed more importance on ECG recording. Doctors ranked ECG recording the highest. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions showed slightly different preferences for athletes compared with coaches and doctors. In cases where arrhythmia was suspected, the value of the HRM’s ability to record ECGs during training by athletes and coaches increased. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups, continuous ECG recording during training will significantly improve the safety of athletes.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110868
The diagnosis and prognosis of tuberculosis remains challenging and necessitates the development of a new test that can accurately diagnose and monitor treatment responses. In this regard, miRNA is becoming a potential diagnostic and prognostic biomarker which differentiates treatment respondents from non-respondents for various non-infectious and infectious diseases, including tuberculosis. The concentration of miRNAs varies based on cell type, disease, and site of infection, implicating that selection of an optimal reference gene is crucial, and determines the quantification of transcript level and biological interpretation of the data. Thus, the study evaluated the stability and expression level of five candidate miRNAs (let-7i-5p, let-7a-5p, miRNA-16-5p, miRNA-22-3p and miRNA-93-5p), including U6 Small Nuclear RNA (RNU6B) to normalize circulating miRNAs in the plasma of 68 participants (26 healthy controls, 23 latent, and 19 pulmonary tuberculosis infected) recruited from four health centers and three hospitals in Addis Ababa, Ethiopia. The expression levels of miRNAs isolated from plasma of culture confirmed newly diagnosed pulmonary tuberculosis patients were compared with latently infected and non-infected healthy controls. The qPCR data were analyzed using four independent statistical tools: Best Keeper, Genorm, Normfinder and comparative delta-Ct methods, and the data showed that miRNA-22-3p and miRNA-93-5p were suitable plasma reference miRNAs in a tuberculosis study.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110864
Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-naïve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003–2.065, p = 0.048; HR: 2.269, 95%CI: 1.053–4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110866
Accurate diagnosis at an early stage of infection is essential for the successful management of any contagious disease. The coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a pandemic that has affected 214 countries affecting more than 37.4 million people causing 1.07 million deaths as of the second week of October 2020. The primary diagnosis of the infection is done either by the molecular technique of RT-qPCR by detecting portions of the RNA of the viral genome or through immunodiagnostic tests by detecting the viral proteins or the antibodies produced by the host. As the demand for the test increased rapidly many naive manufacturers entered the market with novel kits and more and more laboratories also entered the diagnostic arena making the test result more error-prone. There are serious debates globally and regionally on the sensitivity and specificity of these tests and about the overall accuracy and reliability of the tests for decision making on control strategies. The significance of the test is also complexed by the presence of asymptomatic carriers, re-occurrence of infection in cured patients as well as by the varied incubation periods of the infection and shifting of the viral location in the host tissues. In this paper, we review the techniques available for SARS-CoV-2 diagnosis and probable factors that can reduce the sensitivity and specificity of the different test methods currently in vogue. We also provide a checklist of factors to be considered to avoid fallacious practices to reduce false positive and false negative results by the clinical laboratories.
Diagnostics, Volume 10; doi:10.3390/diagnostics10110863
Limited data are available on the prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with adult weight gain (AWG) in the lean population. This study aimed to determine the prevalence of NAFLD and to investigate whether AWG is associated with NAFLD in the lean Japanese population. We retrospectively analyzed patients who underwent abdominal ultrasonography as part of the annual health checkup between January 2019 and December 2019. Participants were classified into two groups: those with AWG ≥ 10 kg (AWG group, n = 497), and those without gain (non-AWG group, n = 3006). To adjust for the confounding effects, we generated 482 pairs using 1:1 propensity score matching. The associations between AWG and NAFLD, anthropometric parameters and NAFLD were investigated using univariate logistic regression analysis. We identified NAFLD in 197 (5.6%) participants. AWG was significantly associated with NAFLD (odds ratio (OR), 1.81; p = 0.003). Waist circumference was significantly associated with NAFLD in both the AWG (OR, 1.24; p < 0.001) and non-AWG groups (OR, 1.17; p < 0.001). The association between body mass index and NAFLD existed in the former group (OR, 1.76; p < 0.001), but was not significant in the latter group. AWG is a risk factor for NAFLD even in the lean Japanese population, and associations between anthropometric parameters and NAFLD become stronger if AWG coexists.