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1.
  • Bajramaj, Ermira, et al. (författare)
  • The Effect of Microdialysis Catheter Insertion on Glutamate and Serotonin Levels in Masseter Muscle in Patients with Myofascial Temporomandibular Disorders and Healthy Controls
  • 2019
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p < 0.001), followed by a significant increase between 120 and 140 min (p < 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects.
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2.
  • Baubeta Fridh, Erik, et al. (författare)
  • Comparison of Magnetic Resonance Angiography and Digital Subtraction Angiography for the Assessment of Infrapopliteal Arterial Occlusive Lesions, Based on the TASC II Classification Criteria
  • 2020
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper aimed to study the agreement and repeatability, both intra- and interobserver, of infrapopliteal lesion assessment with magnetic resonance angiography (MRA), using the TransAtlantic Inter-Society Consensus (TASC) II criteria, with perioperative digital subtraction angiography (DSA) as a reference. Sixty-eight patients with an MRA preceding an endovascular infrapopliteal revascularization were included. Preoperative MRAs and perioperative DSAs were evaluated in random order by three independent observers using the TASC II classification. The results were analyzed using visual grading characteristics (VGC) analysis and Krippendorffs alpha. No systematic difference was found between modalities: area under the VGC curve (AUC(VGC)) = 0.48 (p = 0.58) or intraobserver; AUC(VGC) for Observer 1 and 2 respectively, 0.49 (p = 0.85) and 0.53 (p = 0.52) for MRA compared with 0.54 (p = 0.30) and 0.49 (p = 0.81) for DSA. Interobserver differences were seen: AUC(VGC) of 0.63 (p < 0.01) for DSA and 0.80 (p < 0.01) for MRA. These results were confirmed using Krippendorffs alpha for the three observers showing 0.13 (95% confidence interval (CI) -0.07-0.31) for MRA and 0.39 (95% CI 0.23-0.53) for DSA. Poor interobserver agreement was also found in the choice of a target vessel on preoperative MRA: Krippendorffs alpha = 0.19 (95% CI 0.01-0.36). In conclusion, infrapopliteal lesions can be reliably determined on preoperative MRA, but interobserver variability regarding the choice of a target vessel is a major concern that appears to affect the overall TASC II grade.
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3.
  • Bruno, RR, et al. (författare)
  • Failure of Lactate Clearance Predicts the Outcome of Critically Ill Septic Patients
  • 2020
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Early lactate clearance is an important parameter for prognosis assessment and therapy control in sepsis. Patients with a lactate clearance >0% might differ from patients with an inferior clearance in terms of intensive care management and outcomes. This study analyzes a large collective with regards to baseline risk distribution and outcomes. Methods: In total, 3299 patients were included in this analysis, consisting of 1528 (46%) ≤0% and 1771 (54%) >0% patients. The primary endpoint was intensive care unit (ICU) mortality. Multilevel logistic regression analyses were used to compare both groups: A baseline model (model 1) with lactate clearance as a fixed effect and ICU as a random effect was installed. For model 2, patient characteristics (model 2) were included. For model 3, intensive care treatment (mechanical ventilation and vasopressors) was added to the model. Models 1 and 2 were used to evaluate the primary and secondary outcomes, respectively. Model 3 was only used to evaluate the primary outcomes. Adjusted odds ratios (aORs) with respective 95% confidence intervals (CI) were calculated. Results: The cohorts had no relevant differences regarding the gender, BMI, age, heart rate, body temperature, and baseline lactate. Neither the primary infection focuses nor the ethnic background differed between both groups. In both groups, the most common infection sites were of pulmonary origin, the urinary tract, and the gastrointestinal tract. Patients with lactate clearance >0% evidenced lower sepsis-related organ failure assessment (SOFA) scores (7 ± 6 versus 9 ± 6; p < 0.001) and creatinine (1.53 ± 1.49 versus 1.80 ± 1.67; p < 0.001). The ICU mortality differed significantly (14% versus 32%), and remained this way after multivariable adjustment for patient characteristics and intensive care treatment (aOR 0.43 95% CI 0.36–0.53; p < 0.001). In the additional sensitivity analysis, the lack of lactate clearance was associated with a worse prognosis in each subgroup. Conclusion: In this large collective of septic patients, the 6 h lactate clearance is an independent method for outcome prediction.
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4.
  • Bäckryd, Emmanuel (författare)
  • Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine.
  • 2015
  • Ingår i: Diagnostics. - : MDPI AG. - 1777-781X .- 2075-4418. ; 5:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. "opioid epidemic" is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chronic pain conditions is presented in this non-technical paper, focusing on the need for biomarkers and the theoretical complexity of the task. Pain is and will remain a subjective experience, and as such is not objectively measurable. Therefore, the concept of "noci-marker" is presented as an alternative to "pain biomarker", the goal being to find objective, measurable correlates of the pathophysiological processes involved in different chronic pain conditions. This vision entails a call for more translational pain research in order to bridge the gap between clinical pain medicine and preclinical science.
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5.
  • Celik, Y., et al. (författare)
  • Association of Excessive Daytime Sleepiness with the Zung Self-Rated Depression Subscales in Adults with Coronary Artery Disease and Obstructive Sleep Apnea
  • 2021
  • Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Excessive daytime sleepiness (EDS) is a factor associated with both obstructive sleep apnea (OSA) and depressive symptoms. Continuous positive airway pressure (CPAP) treatment may decrease EDS in adults with OSA; however, the modulatory role of depressive symptoms on the improvement of EDS is not known. We aimed to explore the association between subscales of the Zung Self-rated Depression Scale (SDS) and Epworth Sleepiness Scale (ESS) over a 2-year period in coronary artery disease (CAD) patients with OSA. This was a post-hoc analysis of the RICCADSA cohort, in which 399 adults with CAD (155 sleepy OSA [apnea-hypopnea index >= 15/h] and ESS score >= 10, who were offered CPAP; and 244 nonsleepy OSA [ESS < 10]), randomized to CPAP [n = 122] or no-CPAP [n = 122]) were included. Three factors were extracted from the Zung SDS, based on the principal component analysis: F1, cognitive symptoms and anhedonia; F2, negative mood; and F3, appetite. In a mixed model, the ESS score decreased by 3.4 points (p < 0.001) among the sleepy OSA phenotype, which was predicted by the decline in the F2, but not in the F1 and F3 scores. The fixed effects of time were not significant in the nonsleepy OSA groups, and thus, further analyses were not applicable. Additional within-group analyses showed a significant decrease in all subscales over time both in the sleepy and nonsleepy OSA patients on CPAP whereas there was a significant increase in the nonsleepy OSA group randomized to no-CPAP. We conclude that the improvement in negative mood symptoms of depression, but not changes in cognitive symptoms and anhedonia as well as appetite, was a significant predictor of decline in the ESS scores over a 2-year period in this CAD cohort with sleepy OSA on CPAP treatment.
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6.
  • Cewe, P, et al. (författare)
  • Evaluation of a Novel Teleradiology Technology for Image-Based Distant Consultations: Applications in Neurosurgery
  • 2021
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • In emergency settings, fast access to medical imaging for diagnostic is pivotal for clinical decision making. Hence, a need has emerged for solutions that allow rapid access to images on small mobile devices (SMD) without local data storage. Our objective was to evaluate access times to full quality anonymized DICOM datasets, comparing standard access through an authorized hospital computer (AHC) to a zero-footprint teleradiology technology (ZTT) used on a personal computer (PC) or SMD using national and international networks at a regional neurosurgical center. Image datasets were sent to a senior neurosurgeon, outside the hospital network using either an AHC and a VPN connection or a ZTT (Image Over Globe (IOG)), on a PC or an SMD. Time to access DICOM images was measured using both solutions. The mean time using AHC and VPN was 250 ± 10 s (median 249 s (233–274)) while the same procedure using IOG took 50 ± 8 s (median 49 s (42–60)) on a PC and 47 ± 20 s (median 39 (33–88)) on a SMD. Similarly, an international consultation was performed requiring 23 ± 5 s (median 21 (16–33)) and 27 ± 1 s (median 27 (25–29)) for PC and SMD respectively. IOG is a secure, rapid and easy to use telemedicine technology facilitating efficient clinical decision making and remote consultations.
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7.
  • Chachaj, Annika, et al. (författare)
  • Metabolomics of Interstitial Fluid, Plasma and Urine in Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms
  • 2020
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • There is growing evidence that lymphatic system plays a pivotal role in the pathogenesis of hypertension. Here, for the first time, the metabolome of interstitial fluid is analyzed in patients with arterial hypertension. Due to ethical issues to obtain human interstitial fluid samples, this study included only oncological patients after axillary lymph node dissection (ALND). These patients were matched into hypertensive (n = 29) and normotensive (n = 35) groups with similar oncological status. Simultaneous evaluation of interstitial fluid, plasma, and urine was obtained by combining high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy with chemometric analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) provided a clear differentiation between the hypertension and normotensive group, with the discrimination visible in each biofluid. In interstitial fluid nine potential metabolomic biomarkers for hypertension could be identified (creatinine, proline, pyroglutamine, glycine, alanine, 1-methylhistidine, the lysyl group of albumin, threonine, lipids), seven distinct markers in plasma (creatinine, mannose, isobutyrate, glycine, alanine, lactate, acetate, ornithine), and seven respectively in urine (methylmalonate, citrulline, phenylacetylglycine, fumarate, citrate, 1-methylnicotinamide, trans-aconitate). Biomarkers in plasma and urine allowed for the identification of specific biochemical pathways involved in hypertension, as previously suggested. Analysis of the interstitial fluid metabolome provided additional biomarkers compared to plasma or urine. Those biomarkers reflected primarily alterations in the metabolism of lipids and amino acids, and indicated increased levels of oxidative stress/inflammation in patients with hypertension.
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8.
  • Charitakis, Emmanouil, et al. (författare)
  • Comparing Efficacy and Safety in Catheter Ablation Strategies for Paroxysmal Atrial Fibrillation : A Network Meta-Analysis of Randomized Controlled Trials
  • 2022
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 12:2
  • Forskningsöversikt (refereegranskat)abstract
    • Although catheter ablation (CA) is an established treatment for paroxysmal atrial fibrillation (PAF), there is no consensus regarding the most efficient CA strategy. The objective of this network meta-analysis (NMA) was to compare the efficacy and safety of different CA strategies for PAF. A systematic search was performed in PubMed, Web of Science, and CENTRAL until the final search date, 5 October 2020. Randomised controlled trials (RCT) comparing different CA strategies and methods for pulmonary vein isolation (PVI) were included. Efficacy was defined as lack of arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of six months. In total, 43 RCTs comparing 11 different CA strategies involving 6701 patients were included. The risk of recurrence was significantly decreased in comparison with PVI with radiofrequency only for the following treatments: PVI with adjuvant ablation (RR: 0.79, CI: 0.65-0.97) and PVI with sympathetic modulation (RR: 0.64, CI: 0.46-0.88). However, PVI with radiofrequency was superior to non-PVI strategies (RR: 1.65, CI: 1.2-2.26). No statistically significant difference was found in safety between different CA strategies. Concerning different PVI strategies, no difference was observed either in efficacy or in safety between tested strategies. This NMA suggests that different PVI strategies are generally similar in terms of efficacy, while PVI with additional ablation or sympathetic modulation may be more effective than PVI alone. This study provides decision-makers with insights into the efficacy and safety of different CA strategies.
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9.
  • Christidis, N, et al. (författare)
  • Salivary Alpha-Amylase in Experimentally-Induced Muscle Pain
  • 2020
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Salivary alpha-amylase (sAA) is a marker of psychological stress and might also be a potential marker for pain-associated stress due its non-invasive, cost-effective, and stress-free collection. The current study aimed to investigate whether the levels of sAA are influenced by experimentally induced muscle pain. In this study, 26 healthy, pain-free and age-matched participants (23.8 ± 2.6 years) were included, 13 women and 13 men. Prior to the experiment, questionnaires assessing health and anxiety were completed. Muscle pain was then induced through intramuscular injection of 0.4 mL hypertonic saline (56.5 mg/mL) into the masseter muscle and unstimulated whole saliva samples were collected at baseline before injection, 2 min, and 15 min after injection. A commercially available colorimetric assay was used to analyze the sAA. Perceived pain and stress were assessed using a 0–100 Numeric Rating Scale for each sample. There were no significant differences in sAA levels prior and after injection of hypertonic saline (p > 0.05) although sAA levels showed a slight decrease during experimentally-induced muscle pain. However, a strong correlation was observed between self-reported pain and perceived level of stress during experimentally-induced muscle pain (r2 = 0.744; p < 0.0001). Furthermore, there was a moderate correlation between the levels of sAA at baseline and during experimental pain (r2 = 0.687; p < 0.0001). In conclusion, this study could not show any association between the levels of sAA and perceived pain and or/stress. However, since a significant strong correlation could be observed between perceived stress and pain intensity, this study indicates that experimentally-induced muscle pain could be used as a stress model.
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10.
  • Chyzhma, Ruslana, et al. (författare)
  • Potential role of hydroxyapatite nanocrystalline for early diagnostics of ovarian cancer
  • 2021
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Calcification is one of the clinical and morphological manifestations of ovarian tumors and it begins at the initial stages of carcinogenesis. Thus, this process can be used for the early diagnostics of some malignant ovarian tumors. We compared the results of ultrasound and histology and found that calcifications of a size less than 200 μm are not detected by ultrasound. These calcified structures are round fragile particles of different sizes. In the EDX (Energy-dispersive X-ray spectroscopy) spectra, the main lines were from Ca and P, and the ratio of these elements corresponds to hydroxyapatite. Thus, we established that hydroxyapatite is the main mineral component of ovarian psammoma bodies and could be used for early diagnostics of ovarian malignant neoplasia.
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11.
  • Cunha, Francisco, et al. (författare)
  • A Systematic Review of Asthma Phenotypes Derived by Data-Driven Methods
  • 2021
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:4
  • Forskningsöversikt (refereegranskat)abstract
    • Classification of asthma phenotypes has a potentially relevant impact on the clinical management of the disease. Methods for statistical classification without a priori assumptions (data-driven approaches) may contribute to developing a better comprehension of trait heterogeneity in disease phenotyping. This study aimed to summarize and characterize asthma phenotypes derived by data-driven methods. We performed a systematic review using three scientific databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. We included studies reporting adult asthma phenotypes derived by data-driven methods using easily accessible variables in clinical practice. Two independent reviewers assessed studies. The methodological quality of included primary studies was assessed using the ROBINS-I tool. We retrieved 7446 results and included 68 studies of which 65% (n = 44) used data from specialized centers and 53% (n = 36) evaluated the consistency of phenotypes. The most frequent data-driven method was hierarchical cluster analysis (n = 19). Three major asthma-related domains of easily measurable clinical variables used for phenotyping were identified: personal (n = 49), functional (n = 48) and clinical (n = 47). The identified asthma phenotypes varied according to the sample's characteristics, variables included in the model, and data availability. Overall, the most frequent phenotypes were related to atopy, gender, and severe disease. This review shows a large variability of asthma phenotypes derived from data-driven methods. Further research should include more population-based samples and assess longitudinal consistency of data-driven phenotypes.
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12.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Soluble Levels of CD163, PD-L1, and IL-10 in Renal Cell Carcinoma Patients
  • 2022
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • CD163+ M2 macrophages have been suggested to counteract tumor immunity by increasing immunosuppressive mechanisms including PD-L1 and IL-10 expression. Soluble levels of PD-L1, IL-10, and CD163 have been reported as potential biomarkers in various cancers, although the prognostic value in renal cell carcinoma (RCC) has to be further elucidated. In the present study, we measured the levels of sPD-L1, sIL-10, and sCD163 in 144 blood samples from patients with RCC. The levels were determined by using enzyme linked immunosorbent assays. Soluble PD-L1 and CD163 were detectable in 100% of the serum samples, and sCD163 in 22% of the urine samples, while only a minority of the samples had detectable sIL-10. Significantly higher serum levels of sPD-L1 and sCD163 were observed in patients with metastatic disease (p < 0.05). The results also showed that patients with high levels of sPD-L1 in serum had shorter cancer-specific survival compared with patients with low levels (p = 0.002). The results indicate that sPD-L1 most significantly reflects tumor progression in RCC.
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13.
  • De Palma, FDE, et al. (författare)
  • The Multifaceted Roles of MicroRNAs in Cystic Fibrosis
  • 2020
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Cystic fibrosis (CF) is a lifelong disorder affecting 1 in 3500 live births worldwide. It is a monogenetic autosomal recessive disease caused by loss-of-function mutations in the gene encoding the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR), the impairment of which leads to ionic disequilibria in exocrine organs. This translates into a chronic multisystemic disease characterized by airway obstruction, respiratory infections, and pancreatic insufficiency as well as hepatobiliary and gastrointestinal dysfunction. Molecular characterization of the mutational heterogeneity of CFTR (affected by more than 2000 variants) improved the understanding and management of CF. However, these CFTR variants are linked to different clinical manifestations and phenotypes, and they affect response to treatments. Expanding evidence suggests that multisystemic disease affects CF pathology via impairing either CFTR or proteins regulated by CFTR. Thus, altering the expression of miRNAs in vivo could constitute an appealing strategy for developing new CF therapies. In this review, we will first describe the pathophysiology and clinical management of CF. Then, we will summarize the current knowledge on altered miRNAs in CF patients, with a focus on the miRNAs involved in the deregulation of CFTR and in the modulation of inflammation. We will highlight recent findings on the potential utility of measuring circulating miRNAs in CF as diagnostic, prognostic, and predictive biomarkers. Finally, we will provide an overview on potential miRNA-based therapeutic approaches.
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14.
  • Deding, Ulrik, et al. (författare)
  • Patient-reported outcomes and preferences for colon capsule endoscopy and colonoscopy : A systematic review with meta-analysis
  • 2021
  • Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 11:9
  • Forskningsöversikt (refereegranskat)abstract
    • Colon capsule endoscopy as an alternative to colonoscopy for the diagnosis of colonic disease may serve as a less invasive and more tolerable investigation for patients. Our aim was to examine patient-reported outcomes for colon capsule endoscopy compared to conventional optical colonoscopy including preference of investigation modality, tolerability and adverse events. A systematic literature search was conducted in Web of Science, PubMed and Embase. Search results were thoroughly screened for in-and exclusion criteria. Included studies underwent assessment of transparency and completeness, after which, data for meta-analysis were extracted. Pooled estimates of patient preference were calculated and heterogeneity was examined including univariate meta-regressions. Patient-reported tolerability and adverse events were reviewed. Out of fourteen included studies, twelve had investigated patient-reported outcomes in patients who had undergone both investigations, whereas in two the patients were randomized between investigations. Pooled patient preferences were estimated to be 52% (CI 95%: 41–63%) for colon capsule endoscopy and 45% (CI 95%: 33–57%) for conventional colonoscopy: not indicating a significant difference. Procedural adverse events were rarely reported by patients for either investigation. The tolerability was high for both colon capsule endoscopy and conventional colonoscopy. Patient preferences for conventional colonoscopy and colon capsule endoscopy were not significantly different. Procedural adverse events were rare and the tolerability for colon capsule endoscopy was consistently reported higher or equal to that of conventional colonoscopy.
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15.
  • Fahlström, Markus, et al. (författare)
  • Evaluation of Arterial Spin Labeling MRI : Comparison with 15O-Water PET on an Integrated PET/MR Scanner
  • 2021
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.
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16.
  • Fortarezza, F, et al. (författare)
  • COVID-19 Pulmonary Pathology: The Experience of European Pulmonary Pathologists throughout the First Two Waves of the Pandemic
  • 2022
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoptic studies of patients who died from COVID-19 constitute an important step forward in improving our knowledge in the pathophysiology of SARS-CoV-2 infection. Systematic analyses of lung tissue, the organ primarily targeted by the disease, were mostly performed during the first wave of the pandemic. Analyses of pathological lesions at different times offer a good opportunity to better understand the disease and how its evolution has been influenced mostly by new SARS-CoV-2 variants or the different therapeutic approaches. In this short report we summarize responses collected from a questionnaire survey that investigated important pathological data during the first two pandemic waves (spring-summer 2020; autumn-winter 2020–2021). The survey was submitted to expert lung pathologists from nine European countries involved in autoptic procedures in both pandemic waves. The frequency of each lung lesion was quite heterogeneous among the participants. However, a higher frequency of pulmonary superinfections, both bacterial and especially fungal, was observed in the second wave compared to the first. Obtaining a deeper knowledge of the pathological lesions at the basis of this complex and severe disease, which change over time, is crucial for correct patient management and treatment. Autoptic examination is a useful tool to achieve this goal.
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17.
  • Golub, LM, et al. (författare)
  • An Unexplored Pharmacologic/Diagnostic Strategy for Peri-Implantitis: A Protocol Proposal
  • 2020
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Dental implants are widely utilized for the replacement of missing teeth and are increasingly being placed in patients with systemic diseases, as well as in those who are medically healthy. Furthermore, it is recognized that peri-implant mucositis and peri-implantitis are highly prevalent, affecting large numbers of patients with implants, and it is pertinent to consider whether there may be any systemic impact of these conditions, given that there are known links between periodontitis and a number of chronic inflammatory diseases. In this article, we propose that the potential systemic complications of peri-implant diseases should be investigated in future clinical research, together with studies to identify whether systemically-administered host modulation therapies (HMTs) may be of benefit in the treatment of peri-implant diseases. These “HMTs” may prove a useful adjunct to routinely employed debridement and disinfection protocols, as well as potentially being of benefit in reducing risks of systemic complications. We also consider the use of chair-side diagnostic tests for active matrix metalloproteinase-8 (aMMP-8) in the detection of peri-implant disease given the ability of such tests to detect active tissue breakdown associated with peri-implantitis and periodontitis before conventional clinical and radiographic measurements indicate pathologic changes. These novel diagnostic and therapeutic strategies are relevant to consider as they may improve the management of peri-implant disease (beyond local debridement procedures), especially in those patients in whom systemic inflammation might be of concern.
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18.
  • Grigoriadis, A, et al. (författare)
  • Prediabetes/Diabetes Can Be Screened at the Dental Office by a Low-Cost and Fast Chair-Side/Point-of-Care aMMP-8 Immunotest
  • 2019
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Pre-diabetes and diabetes are strongly associated with periodontal disease (gingivitis and periodontitis), and these conditions are known to upregulate aMMP-8 in inflamed gingiva and oral fluids. Thus, it would be feasible to screen for prediabetes and diabetes at the dental office by chairside tests. Chair-side assessment of HbA1c and a quantitative point-of-care (PoC) active matrix metalloproteinase (aMMP)-8 oral rinse immunotest developed for periodontal diseases, were performed on patients (n = 69) attending a Periodontology University Clinic who fulfilled the criteria for testing according to the screening questionnaire of the Centers for Disease Control and Prevention, USA. Clinical parameters of periodontal disease were also recorded with an automated probe. Twenty seven-point-five percent of the subjects were found with previously unknown hyperglycemia (HbA1c ≥ 5.7%). There was a statistically-significant positive association between the aMMP-8test and prediabetes (p < 0.05, unadjusted and adjusted for BMI and age ≥ 45 years logistic regression models). The dental setting is suitable for opportunistic screening for undiagnosed diabetes and pre-diabetes and point-of-care HbA1c, especially when combined with aMMP-8 assessment by dental professionals, being convenient and effective.
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19.
  • Henein, Michael Y., et al. (författare)
  • Coronary Atherosclerosis Imaging
  • 2020
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 10:2
  • Forskningsöversikt (refereegranskat)abstract
    • Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. However, atherosclerosis is a dynamic process and the plaque morphology and composition may change over time. Most vulnerable plaques undergo progressive transformation from high-risk to more stable and heavily calcified lesions, while others undergo subclinical rupture and healing. Although extensive plaque calcification is often associated with stable atherosclerosis, the extent of coronary artery calcification strongly correlates with the degree of atherosclerosis and with the rate of future cardiac events. Inflammation has a central role in atherogenesis, from plaque formation to rupture, hence in the development of acute coronary events. Morphologic plaque assessment, both invasive and non-invasive, gives limited information as to the current activity of the atherosclerotic disease. The addition of nuclear imaging, based on radioactive tracers targeted to the inflammatory components of the plaques, provides a highly sensitive assessment of coronary disease activity, thus distinguishing those patients who have stable disease from those with active plaque inflammation.
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20.
  • Hernandez, M, et al. (författare)
  • Active MMP-8 Quantitative Test as an Adjunctive Tool for Early Diagnosis of Periodontitis
  • 2021
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Periodontitis is a host-mediated bacterial disease that affects the tooth attachment apparatus. Metalloproteinase-8 (MMP-8), a validated biomarker, could aid in clinical diagnosis. This study aimed to evaluate the diagnostic performance of active (a) MMP-8 immunotest versus total (t) MMP-8 ELISA for quantitative real-time diagnosis and assessment of periodontitis severity at the site level. Gingival crevicular fluid (GCF) was sampled from 30 healthy, 42 mild, and 59 severe periodontitis sites from thirty-one volunteers. MMP-8 concentrations were determined by time-resolved immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the STATA package. Both active and total MMP-8-based methods discriminated among sites according to periodontal diagnosis and severity, with a positive correlation between the two tests (p < 0.001). (a) MMP-8 models showed the best performance in receiver operating characteristic (ROC) curves to discriminate between healthy and periodontitis sites (area under the curve [AUC] = 0.89), while (t) MMP-8 demonstrated a high diagnostic precision in the detection of mild from severe periodontitis sites (AUC ≥ 0.80). The use of (a) MMP-8 and (t) MMP-8 could represent a useful adjunctive tool for periodontitis diagnosis and severity. These results support the applicability of new point-of-care methods in the monitoring of high-risk periodontal patients.
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21.
  • Jonmarker, O, et al. (författare)
  • Comparison of Regularized Reconstruction and Ordered Subset Expectation Maximization Reconstruction in the Diagnostics of Prostate Cancer Using Digital Time-of-Flight 68Ga-PSMA-11 PET/CT Imaging
  • 2021
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In prostate cancer, the early detection of distant spread has been shown to be of importance. Prostate-specific membrane antigen (PSMA)-binding radionuclides in positron emission tomography (PET) is a promising method for precise disease staging. PET diagnostics depend on image reconstruction techniques, and ordered subset expectation maximization (OSEM) is the established standard. Block sequential regularized expectation maximization (BSREM) is a more recent reconstruction algorithm and may produce fewer equivocal findings and better lesion detection. Methods: 68Ga PSMA-11 PET/CT scans of patients with de novo or suspected recurrent prostate cancer were retrospectively reformatted using both the OSEM and BSREM algorithms. The lesions were counted and categorized by three radiologists. The intra-class correlation (ICC) and Cohen’s kappa for the inter-rater reliability were calculated. Results: Sixty-one patients were reviewed. BSREM identified slightly fewer lesions overall and fewer equivocal findings. ICC was excellent with regards to definitive lymph nodes and bone metastasis identification and poor with regards to equivocal metastasis irrespective of the reconstruction algorithm. The median Cohen’s kappa were 0.66, 0.74, 0.61 and 0.43 for OSEM and 0.61, 0.63, 0.66 and 0.53 for BSREM, with respect to the tumor, local lymph nodes, metastatic lymph nodes and bone metastasis detection, respectively. Conclusions: BSREM in the setting of 68Ga PMSA PET staging or restaging is comparable to OSEM.
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22.
  • Karah, Nabil, et al. (författare)
  • Guideline for Urine Culture and Biochemical Identification of Bacterial Urinary Pathogens in Low-Resource Settings
  • 2020
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 10:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Medical diagnosis in low-resource settings is confronted by the lack of suitable guidelines, protocols and checklists. Online-accessible procedural documents are difficult to find, might be mistranslated or interpreted and usually do not address the needs of developing countries. Urinalysis, one of the most frequently performed diagnostic examinations worldwide, involves a series of tests aiming to detect particular disorders, such as urinary tract infections, kidney disease and diabetes. In this guideline, we present an alternative approach for clinical laboratories with limited resources to identify common bacterial uropathogens. We propose dividing the identification plan into two levels. The implicated pathogen will first be assigned into a bacterial group, basic identification, against which a suitable panel of antimicrobial agents shall be selected for the antimicrobial susceptibility testing (AST). Characterization of the pathogen to the genus or species level, advanced identification, will then be performed to ensure correct reading of the AST results and determine the epidemiology of clinically significant pathogens. Most of the proposed steps in our guideline are tailored to meet the needs of clinical laboratories in low-resource settings. Such guidelines are needed to strengthen the capacity of regional pathology laboratories and to enhance international initiatives on antimicrobial resistance and health equity.
  •  
23.
  • Koivisto, K, et al. (författare)
  • The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging
  • 2019
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini–Hochberg (B–H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP-10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.
  •  
24.
  • Koivuholma, A, et al. (författare)
  • Three-Dimensional Presentation of Tumor Histopathology: A Model Using Tongue Squamous Cell Carcinoma
  • 2021
  • Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Medical imaging often presents objects in three-dimensional (3D) form to provide better visual understanding. In contrast, histopathology is typically presented as two-dimensional (2D). Our objective was to present the tumor dimensions in 3D by creating a 3D digital model of it and so demonstrate the location of the tumor and the histological slices within the surgical soft tissue resection specimen. We developed a novel method for modeling a tongue squamous cell carcinoma using commonly available instruments. We established our 3D-modeling method by recognizing and solving challenges that concern the selection of the direction of histological slices. Additional steps to standard handling included scanning the specimen prior to grossing and modeling the carcinoma, which required only a table scanner and modeling software. We present challenges and their solutions in modeling the resection specimen and its histological slices. We introduce a finished 3D model of a soft tissue resection specimen and the actual tumor as well as its histopathological grossing sites in 3D digital and printed form. Our novel method provides steps to create a digital model of soft tissue resection specimen and the tumor within. To our knowledge, this is the first attempt to present histopathological margins of a tongue tumor in 3D form, whereas previously, only 2D has been available. The creation of the 3D model does not call for predetermined grossing directions for the pathologist. In addition, it provides a crucial initiative to enhance oncological management. The method allows a better visual understanding of tumor margins, topography, and orientation. It thus provides a tool for an improved postoperative assessment and aids, for example, in the discussion of the need for additional surgery and adjuvant therapy.
  •  
25.
  • Lager, Malin, et al. (författare)
  • Molecular Detection of Borrelia Bacteria in Cerebrospinal Fluid-Optimisation of Pre-Analytical Sample Handling for Increased Analytical Sensitivity
  • 2021
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The main tools for clinical diagnostics of Lyme neuroborreliosis (LNB) are based on serology, i.e., detection of antibodies in cerebrospinal fluid (CSF). In some cases, PCR may be used as a supplement, e.g., on CSF from patients with early LNB. Standardisation of the molecular methods and systematic evaluation of the pre-analytical handling is lacking. To increase the analytical sensitivity for detection of Borrelia bacteria in CSF by PCR targeting the 16S rRNA gene, parameters were systematically evaluated on CSF samples spiked with a known amount of cultured Borrelia bacteria. The results showed that the parameters such as centrifugation time and speed, the use of complementary DNA as a template (in combination with primers and a probe aiming at target gene 16S rRNA), and the absence of inhibitors (e.g., erythrocytes) had the highest impact on the analytical sensitivity. Based on these results, a protocol for optimised handling of CSF samples before molecular analysis was proposed. However, no clinical evaluation of the proposed protocol has been done so far, and further investigations of the diagnostic sensitivity need to be performed on well-characterised clinical samples from patients with LNB.
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