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J. Clin. Med., Volume 9, Issue 3 (March 2020) – 282 articles

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Cover Story (view full-size image) Glucocerebrosidase (GCase) is a retaining β-glucosidase hydrolysing the glycosphingolipid [...] Read more.
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Open AccessArticle
The Wearable Cardioverter-Defibrillator: Experience in 153 Patients and a Long-Term Follow-Up
J. Clin. Med. 2020, 9(3), 893; https://doi.org/10.3390/jcm9030893 (registering DOI) - 24 Mar 2020
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Abstract
Background: The wearable cardioverter-defibrillator (WCD) is available for patients at high risk for sudden cardiac death (SCD) when immediate implantable cardioverter-defibrillator (ICD) implantation is not possible or indicated. Patient selection remains challenging especially in primary prevention. Long-term data on these patients is still [...] Read more.
Background: The wearable cardioverter-defibrillator (WCD) is available for patients at high risk for sudden cardiac death (SCD) when immediate implantable cardioverter-defibrillator (ICD) implantation is not possible or indicated. Patient selection remains challenging especially in primary prevention. Long-term data on these patients is still lacking. Methods: 153 patients were included in this study. They were prescribed the WCD between April 2012 and March 2019 at the University Medical Center, Mannheim, Germany. The mean follow-up period was 36.2 ± 15.6 months. Outcome data, including all-cause mortality, were analyzed by disease etiology and ICD implantation following WCD use. Results: We analyzed 56 patients with ischemic cardiomyopathy, 70 patients with non-ischemic cardiomyopathy, 16 patients with prior need for ICD/CRT-D (device for cardiac resynchronization therapy with defibrillator) explanation, 8 patients with acute myocarditis and 3 patients with congenital diseases. 58% of the patients did not need ICD/CRT-D implantation after WCD use. 4% of all patients suffered from appropriate WCD shocks. 2 of these patients (33%) experienced appropriate ICD shocks after implantation due to ventricular tachyarrhythmias. Long-term follow-up shows a good overall survival. All-cause mortality was 10%. There was no significant difference between patients with or without subsequent ICD implantation (p = 0.48). Patients with ischemic cardiomyopathy numerically showed a higher long-term mortality than patients with non-ischemic cardiomyopathy (14% vs. 6%, p = 0.13) and received significantly more ICD shocks after implantation (10% of ischemic cardiomyopathy (ICM) patients versus 3% of non-ischemic cardiomyopathy (NICM) patients, p = 0.04). All patients with ventricular tachyarrhythmias during WCD use or after ICD implantation survived the follow-up period. Conclusion: Following WCD use, ICD implantation could be avoided in 58% of patients. Long-term follow-up shows good overall survival. The majority of all patients did not suffer from WCD shocks nor did receive ICD shocks after subsequent implantation. Patient selection regarding predictive conditions on long-term risk of ventricular tachyarrhythmias needs further risk stratification. Full article
(This article belongs to the Special Issue New Approaches to the Atrial Fibrillation Management)
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Open AccessReview
Mitophagy in Cardiovascular Diseases
J. Clin. Med. 2020, 9(3), 892; https://doi.org/10.3390/jcm9030892 (registering DOI) - 24 Mar 2020
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Abstract
Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the [...] Read more.
Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes. Full article
(This article belongs to the Special Issue The Rise of Mitochondria in Medicine)
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Open AccessArticle
Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
J. Clin. Med. 2020, 9(3), 891; https://doi.org/10.3390/jcm9030891 - 24 Mar 2020
Viewed by 222
Abstract
Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 [...] Read more.
Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood. Methods: We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4. Results: IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1. Conclusions: Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD. Full article
(This article belongs to the Section Dermatology)
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Open AccessReview
In Which Patients with Sarcoidosis Is FDG PET/CT Indicated?
J. Clin. Med. 2020, 9(3), 890; https://doi.org/10.3390/jcm9030890 (registering DOI) - 24 Mar 2020
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Abstract
Sarcoidosis is a granulomatous disease of which the etiology remains unknown. The diverse clinical manifestations may challenge clinicians, particularly when conventional markers are inconclusive. From various studies, it has become clear that fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT aids in sarcoidosis care. In [...] Read more.
Sarcoidosis is a granulomatous disease of which the etiology remains unknown. The diverse clinical manifestations may challenge clinicians, particularly when conventional markers are inconclusive. From various studies, it has become clear that fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT aids in sarcoidosis care. In this article, an update on FDG PET/CT in sarcoidosis is provided. The use of FDG PET/CT in the diagnostic process of sarcoidosis is explained, especially in determining treatable inflammatory lesions in symptomatic patients with indecisive conventional tests. Furthermore, FDG PET/CT for evaluating the potential benefit of additional inflammatory treatment is described and its use in cardiac sarcoidosis is highlighted. Full article
(This article belongs to the Special Issue Management of Sarcoidosis: Challenges and Solutions)
Open AccessArticle
Tc-99m TRODAT-1 SPECT is a Potential Biomarker for Restless Leg Syndrome in Patients with End-Stage
J. Clin. Med. 2020, 9(3), 889; https://doi.org/10.3390/jcm9030889 - 24 Mar 2020
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Abstract
Rationales: Restless leg syndrome (RLS) is a common complication in patients with end-stage renal disease (ESRD). However, there is a lack of biomarkers linking uremic RLS to dopaminergic neurons. Previous studies demonstrated that Tc-99m TRODAT-1 SPECT was a biomarker for RLS but the [...] Read more.
Rationales: Restless leg syndrome (RLS) is a common complication in patients with end-stage renal disease (ESRD). However, there is a lack of biomarkers linking uremic RLS to dopaminergic neurons. Previous studies demonstrated that Tc-99m TRODAT-1 SPECT was a biomarker for RLS but the correlation between the physiologic parameter was lacking. Methods: Overall, 32 patients were enrolled in the study and divided into the following 3 groups: (1) control (n = 13), (2) ESRD without RLS (n = 8) and (3) ESRD with RLS (n = 11). All patients had a clinical diagnosis of RLS and received Tc-99m TRODAT-1 SPECT. A subgroup analysis was performed to compare differences between the control and ESRD with RLS groups. Tc-99m TRODAT-1 SPECT was performed and activities in the striatum and occipital areas were measured using manually delineated regions of interest (ROIs) by an experienced nuclear medicine radiologist who was blinded to clinical data. Results: The total ratio of Tc-99m TRODAT SPECT was lower in the ESRD with RLS group (p = 0.046). The uptake ratio of TRODAT negatively correlated with serum parathyroid hormone (r = −0.577, p = 0.015) and ferritin (r = −0.464, p = 0.039) concentrations. However, the uptake positively correlated with the hemoglobin concentration (r = 0.531, p = 0.011). The sensitivity and specificity of the total TRODAT ratio for predicting RLS in the overall population were 95.0% and 67.7%, respectively, at a cutoff value of 0.980 (area under the curve of receiver operating characteristic curve was 0.767, p = 0.024). Conclusion: In patients with ESRD and RLS, Tc-99m TRODAT might be a potential biomarker. Dysregulated hemoglobin, serum parathyroid hormone and serum ferritin concentrations might influence the uptake of the TRODAT ratio. Full article
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Open AccessCommunication
Treatment of Obstructive Sleep Apnea in Children: Handling the Unknown with Precision
J. Clin. Med. 2020, 9(3), 888; https://doi.org/10.3390/jcm9030888 - 24 Mar 2020
Viewed by 175
Abstract
Treatment approaches to pediatric obstructive sleep apnea (OSA) have remarkably evolved over the last two decades. From an a priori assumption that surgical removal of enlarged upper airway lymphadenoid tissues (T&A) was curative in the vast majority of patients as the recommended first-line [...] Read more.
Treatment approaches to pediatric obstructive sleep apnea (OSA) have remarkably evolved over the last two decades. From an a priori assumption that surgical removal of enlarged upper airway lymphadenoid tissues (T&A) was curative in the vast majority of patients as the recommended first-line treatment for pediatric OSA, residual respiratory abnormalities are frequent. Children likely to manifest persistent OSA after T&A include those with severe OSA, obese or older children, those with concurrent asthma or allergic rhinitis, children with predisposing oropharyngeal or maxillomandibular factors, and patients with underlying medical conditions. Furthermore, selection anti-inflammatory therapy or orthodontic interventions may be preferable in milder cases. The treatment options for residual OSA after T&A encompass a large spectrum of approaches, which may be complementary, and clearly require multidisciplinary cooperation. Among these, continuous positive airway pressure (CPAP), combined anti-inflammatory agents, rapid maxillary expansion, and myofunctional therapy are all part of the armamentarium, albeit with currently low-grade evidence supporting their efficacy. In this context, there is urgent need for prospective evidence that will readily identify the correct candidate for a specific intervention, and thus enable some degree of scientifically based precision in the current one approach fits all model of pediatric OSA medical care. Full article
Open AccessArticle
Metabolomic Analysis Reveals Distinct Profiles in the Plasma and Urine Associated with IgE Reactions in Childhood Asthma
J. Clin. Med. 2020, 9(3), 887; https://doi.org/10.3390/jcm9030887 (registering DOI) - 24 Mar 2020
Viewed by 143
Abstract
Several metabolomics studies have identified altered metabolic pathways that are related to asthma. However, an integrative analysis of the metabolic responses across blood and urine for a comprehensive framework of asthma in early childhood remains lacking. Fifty-four age-matched children with asthma (n = [...] Read more.
Several metabolomics studies have identified altered metabolic pathways that are related to asthma. However, an integrative analysis of the metabolic responses across blood and urine for a comprehensive framework of asthma in early childhood remains lacking. Fifty-four age-matched children with asthma (n = 28) and healthy controls (n = 26) were enrolled. Metabolome analysis of the plasma and urine samples was performed using 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Integrated analysis of blood and urine metabolic profiling related to IgE reactions for childhood asthma was investigated. A significantly higher plasma histidine level was found, in parallel with lower urinary 1-methylnicotinamide and trimethylamine N-oxide (TMAO) levels, in children with asthma compared to healthy controls. Compared to children without allergic sensitization, 11 (92%) plasma metabolites and 8 (80%) urinary metabolites were found to be significantly different in children with IgE and food sensitization respectively. There were significant correlations between the plasma 3-hydroxybutyric acid and excreted volumes of the hydroxy acids, which were strongly correlated to plasma leucine and valine levels. Urine N-phenylacetylglycine, a microbial-host co-metabolite, was strongly correlated with total serum and food allergen-specific IgE levels. Plasma pyruvate and urine valine, leucine, and isoleucine degradation metabolisms were significantly associated with allergic sensitization for childhood asthma. In conclusion, blood and urine metabolome reflect different metabolic pathways in allergic reactions. Plasma pyruvate metabolism to acetic acid appears to be associated with serum IgE production, whereas urine branched-chain amino acid metabolism primarily reflects food allergic reactions against allergies. Full article
(This article belongs to the Section Pulmonology)
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Open AccessArticle
Novel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study
J. Clin. Med. 2020, 9(3), 886; https://doi.org/10.3390/jcm9030886 (registering DOI) - 24 Mar 2020
Viewed by 144
Abstract
Background: Chronic kidney disease (CKD) and cardiovascular diseases (CVD) often occur concomitantly, and CKD is a major risk factor for cardiovascular mortality. Since some of the most commonly used biomarkers in CVD are permanently elevated in patients with CKD, novel biomarkers are warranted [...] Read more.
Background: Chronic kidney disease (CKD) and cardiovascular diseases (CVD) often occur concomitantly, and CKD is a major risk factor for cardiovascular mortality. Since some of the most commonly used biomarkers in CVD are permanently elevated in patients with CKD, novel biomarkers are warranted for clinical practice. Methods: Plasma concentrations of five cardiovascular biomarkers (soluble suppression of tumorigenicity (sST2), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor-binding protein 2 (IGF-BP2), and soluble urokinase plasminogen activator receptor) were analyzed by means of enzyme-linked immunosorbent assay (ELISA) in 219 patients with CKD enrolled in the German Chronic Kidney Disease (GCKD) study. Results: Except for sST2, all of the investigated biomarkers were significantly elevated in patients with CKD (2.0- to 4.4-fold increase in advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² body surface area (BSA)) and showed a significant inverse correlation with eGFR. Moreover, all but H-FABP and sST2 were additionally elevated in patients with micro- and macro-albuminuria. Conclusions: Based on our findings, sST2 appears to be the biomarker whose diagnostic performance is least affected by decreased renal function, thus suggesting potential viability in the management of patients with CVD and concomitant CKD. The predictive potential of sST2 remains to be proven in endpoint studies. Full article
(This article belongs to the Special Issue Novel Biomarkers for Heart Disease)
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Open AccessArticle
Effects of Self-Care for Older PErsons (SCOPE) on Functional and Physiological Measures: A Cluster Randomized Controlled Trial
J. Clin. Med. 2020, 9(3), 885; https://doi.org/10.3390/jcm9030885 - 24 Mar 2020
Viewed by 147
Abstract
Background: Population aging poses unprecedented demands on the healthcare system. There is also a scarcity of evidence on self-care intervention to improve objective measures of morbidity and aging-associated functional and physiological measures in a low-income multi-ethnic population setting. Methods: We conducted a cluster [...] Read more.
Background: Population aging poses unprecedented demands on the healthcare system. There is also a scarcity of evidence on self-care intervention to improve objective measures of morbidity and aging-associated functional and physiological measures in a low-income multi-ethnic population setting. Methods: We conducted a cluster randomized controlled trial (ClinicalTrials.gov Identifier: NCT01672177) to examine the effects of the Self-Care for Older PErsons (SCOPE) program. We randomized 14 Senior Activity Centers and randomly selected older adults within these centers. Functional and physiological measurements were performed at baseline, 10-month, and 18-month periods. The primary outcome was a composite of three morbidity-specific measures, which include hemoglobin A1c (HbA1C), peak expiratory flow, and systolic blood pressure. Aging-associated functional and physiological measures were examined as secondary outcomes. Repeated-measure mixed models were employed to examine the effects of SCOPE on these measures. Results: 378 community-dwelling older adults participated in either the treatment (n= 164) or the control arm (n = 214). The primary outcome was not significantly improved. For the secondary outcomes, SCOPE participants demonstrated slower oxygen desaturation at an 18-month period (p = 0.001), improved time to complete the chair-stand test (p < 0.001) at a 10-month period with the effect persisting at the 18-month period (p < 0.001). SCOPE participants also had significantly improved vitamin B12 levels at the 18-month period (p < 0.001), increased hemoglobin concentration (p < 0.001), decreased mean corpuscular volume (p = 0.001), and decreased creatinine (p = 0.002) at the 10-month period. Conclusions: SCOPE did not improve morbidity-specific measures. However, it improved several aging-associated measures implicated in geriatric syndromes. This study highlights the potential of a self-care program in the prevention of geriatric syndromes in community-dwelling older adults, while emphasizing self-management to manage existing morbidities. Full article
(This article belongs to the Special Issue Self-Management and Health Promotion in Chronic Disease)
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Open AccessArticle
Delayed Reconstruction of Palatomaxillary Defect Using Fibula Free Flap
J. Clin. Med. 2020, 9(3), 884; https://doi.org/10.3390/jcm9030884 (registering DOI) - 24 Mar 2020
Viewed by 153
Abstract
Introduction. The objective of this study was to evaluate a surgical technique and to present the results of delayed reconstruction of palatomaxillary defects using fibula free flap (FFF). Methods. A review was conducted for nine patients who underwent palatomaxillary reconstruction using FFF. Primary [...] Read more.
Introduction. The objective of this study was to evaluate a surgical technique and to present the results of delayed reconstruction of palatomaxillary defects using fibula free flap (FFF). Methods. A review was conducted for nine patients who underwent palatomaxillary reconstruction using FFF. Primary disease, type of reconstruction, defect area, fibula segment length and number of osteotomies, radiotherapy, and implant installation after FFF reconstruction were analyzed. Results. All nine patients underwent delayed reconstruction. The fibula shaft was osteotomized into two segments in seven patients and three segments in one patient with bilateral Brown’s revised classification IV/d defect. One case was planned by using a computer-aided design computer-aided manufacturing (CAD/CAM) system with a navigation system. The mean length of the grafted fibula bone was 68.06 mm. Dental implant treatment was performed in six patients. Six patients received radiation therapy, and there were no specific complications related to the radiation therapy. In one case, the defect was reconstructed with FFF flow-through from a radial forearm free flap. Conclusion. This clinical study demonstrated that the fibula flap is an ideal donor-free flap in a palatomaxillary defect. Delayed reconstruction using an FFF can reduce the complication and failure rates. Full article
(This article belongs to the Special Issue Innovation in Head and Neck Reconstructive Surgery)
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Open AccessArticle
Changes in the Retinal Microvasculature Measured Using Optical Coherence Tomography Angiography According to Age
J. Clin. Med. 2020, 9(3), 883; https://doi.org/10.3390/jcm9030883 - 24 Mar 2020
Viewed by 138
Abstract
In this cross-sectional study, we examined age-related changes in the retinal vessels of 100 healthy participants, aged from 5 to 80 years, and divided into four groups (G1, under 20 years of age; G2, from 20 to 39 years of age; G3, from [...] Read more.
In this cross-sectional study, we examined age-related changes in the retinal vessels of 100 healthy participants, aged from 5 to 80 years, and divided into four groups (G1, under 20 years of age; G2, from 20 to 39 years of age; G3, from 40 to 59 years of age; G4, age 60 years or older). All subjects underwent swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). The vascular density (VD) of the superficial (SCP) and deep capillary plexus (DCP), and choriocapillaris (CCP) were measured using OCTA. The vascular density of each capillary layer, foveal avascular zone (FAZ) area, ganglion cell-inner plexiform layer (GC-IPL) thickness, retinal thickness (RT), and choroidal thickness (CT) were compared between age groups. Most OCT variables were correlated with OCTA variables. The FAZ area; VD of the SCP, DCP, and CCP; GC-IPL thickness; RT; and CT showed significant difference (p < 0.001) between G1 + G2 and G3 + G4, except for central GC-IPL thickness (p = 0.14) and central RT (p = 0.25). Density of the retinal capillary vasculature reduced and FAZ area increased after age 40, which represents the onset of middle age. Full article
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Open AccessReview
A Systematic Review of the Effectiveness of Non-Invasive Brain Stimulation Techniques to Reduce Violence Proneness by Interfering in Anger and Irritability
J. Clin. Med. 2020, 9(3), 882; https://doi.org/10.3390/jcm9030882 - 24 Mar 2020
Viewed by 181
Abstract
The field of neurocriminology has proposed several treatments (e.g., pharmacological, brain surgery, androgen-deprivation therapy, neurofeedback) to reduce violence proneness, but unfortunately, their effectiveness has been limited due to their side-effects. Therefore, it is necessary to explore alternative techniques to improve patients’ behavioural regulation [...] Read more.
The field of neurocriminology has proposed several treatments (e.g., pharmacological, brain surgery, androgen-deprivation therapy, neurofeedback) to reduce violence proneness, but unfortunately, their effectiveness has been limited due to their side-effects. Therefore, it is necessary to explore alternative techniques to improve patients’ behavioural regulation with minimal undesirable effects. In this regard, non-invasive brain stimulation techniques, which are based on applying changing magnetic fields or electric currents to interfere with cortical excitability, have revealed their usefulness in alleviating the symptomatology of several mental disorders. However, to our knowledge, there are no reviews that assess whether these techniques are useful for reducing violence proneness. Therefore, we conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria using the following databases: PsycINFO, PubMed, Dialnet, Psicodoc, Web of Knowledge, and the Cochrane Library. We initially identified 3746 entries, and eventually included 56 publications. Most of the studies were unanimous in concluding that the application of these techniques over the prefrontal cortex (PFC) was not sufficient to promote anger and irritability reductions in euthymic individuals of both genders. Nevertheless, the application of non-invasive brain stimulation techniques, especially transcranial direct current stimulation, over the right PFC seemed to reduce violent reactions in these individuals by interfering with the interpretation of the unfavourable situations (e.g., threating signals) or inner states that evoked anger. In antisocial and pathological populations, the conclusions were provided by a few pilot studies with important methodological weaknesses. The main conclusion of these studies was that bilateral stimulation of the PFC satisfactorily reduced anger and irritability only in inmates, patients with autism spectrum disorders (ASD), people who suffered a closed-head injury, and agitated patients with Alzheimer’s disease. Moreover, combining these techniques with risperidone considerably reduced aggressiveness in these patients. Therefore, it is necessary to be cautious about the benefits of these techniques to control anger, due the methodological weaknesses of these studies. Nonetheless, they offer valuable opportunities to prevent violence by designing new treatments combining brain stimulation with current strategies, such as psychotherapy and psychopharmacology, in order to promote lasting changes. Full article
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Open AccessArticle
High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes
J. Clin. Med. 2020, 9(3), 881; https://doi.org/10.3390/jcm9030881 - 24 Mar 2020
Viewed by 185
Abstract
High-frequency near-infrared diode laser provides a high-peak output, low-heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser irradiation in in vitro or in vivo OA models has not yet been [...] Read more.
High-frequency near-infrared diode laser provides a high-peak output, low-heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser irradiation in in vitro or in vivo OA models has not yet been reported. Therefore, we aimed to assess the biological effects of high-frequency near-infrared diode laser irradiation on IL-1β-induced chondrocyte inflammation in an in vitro OA model. Normal Human Articular Chondrocyte-Knee (NHAC-Kn) cells were stimulated with human recombinant IL-1β and irradiated with a high-frequency near-infrared diode laser (910 nm, 4 or 8 J/cm2). The mRNA and protein expression of relevant inflammation- and cartilage destruction-related proteins was analyzed. Interleukin (IL) -1β treatment significantly increased the mRNA levels of IL-1β, IL-6, tumor necrosis factor (TNF) -α, matrix metalloproteinases (MMP) -1, MMP-3, and MMP-13. High-frequency near-infrared diode laser irradiation significantly reduced the IL-1β-induced expression of IL-1β, IL-6, TNF-α, MMP-1, and MMP-3. Similarly, high-frequency near-infrared diode laser irradiation decreased the IL-1β-induced increase in protein expression and secreted levels of MMP-1 and MMP-3. These results highlight the therapeutic potential of high-frequency near-infrared diode laser irradiation in OA. Full article
(This article belongs to the Special Issue Applications of Therapeutic Ultrasound in Dentistry)
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Open AccessEditorial
Special Issue: Sleep Bruxism—The Controversial Sleep Movement Activity
J. Clin. Med. 2020, 9(3), 880; https://doi.org/10.3390/jcm9030880 (registering DOI) - 23 Mar 2020
Viewed by 208
Abstract
According to the current approach [1], bruxism is considered as two different behaviours observed during sleep and wakefulness, respectively, and the single definition for bruxism has been replaced by two separate definitions: Sleep bruxism is a masticatory muscle activity during sleep that is [...] Read more.
According to the current approach [1], bruxism is considered as two different behaviours observed during sleep and wakefulness, respectively, and the single definition for bruxism has been replaced by two separate definitions: Sleep bruxism is a masticatory muscle activity during sleep that is characterised as rhythmic (phasic) or non-rhythmic (tonic) and is not a movement disorder or a sleep disorder in otherwise healthy individuals [...] Full article
(This article belongs to the Special Issue Sleep Bruxism—The Controversial Sleep Movement Activity)
Open AccessReview
Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?
J. Clin. Med. 2020, 9(3), 879; https://doi.org/10.3390/jcm9030879 - 23 Mar 2020
Viewed by 208
Abstract
The final decision to accept an organ for transplantation remains a subjective one. With “poor organ quality” commonly cited as a major reason for kidney discard, accurate, objective, and reliable quality assessment is essential. In an era of increasingly higher-risk deceased donor kidneys, [...] Read more.
The final decision to accept an organ for transplantation remains a subjective one. With “poor organ quality” commonly cited as a major reason for kidney discard, accurate, objective, and reliable quality assessment is essential. In an era of increasingly higher-risk deceased donor kidneys, the catch is to accept those where the risk–benefit scale will tip in the right direction. Currently available assessment tools, such as risk-scores predicting outcome and zero-time biopsy, perform unsatisfactory, and assessment options during static cold storage are limited. Kidney perfusion technologies are finding their way into clinical practice, and they bring a new opportunity to assess kidney graft viability and quality, both in hypothermic and normothermic conditions. We give an overview of the current understanding of kidney viability assessment during ex situ kidney perfusion. A pragmatic framework to approach viability assessment is proposed as an interplay of three different compartments: the nephron, the vascular compartment, and the immune compartment. Although many interesting ways to assess kidney injury and function during perfusion have been proposed, none have reached the stage where they can reliably predict posttransplant outcome. Larger well-designed studies and validation cohorts are needed to provide better guidance. Full article
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Open AccessReview
Natural History of Arrhythmogenic Cardiomyopathy
J. Clin. Med. 2020, 9(3), 878; https://doi.org/10.3390/jcm9030878 (registering DOI) - 23 Mar 2020
Viewed by 213
Abstract
Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a scarred ventricular myocardium with a distinctive propensity to ventricular arrhythmias (VAs) and sudden cardiac death, especially in young athletes. Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents the best characterized variant of AC, with [...] Read more.
Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a scarred ventricular myocardium with a distinctive propensity to ventricular arrhythmias (VAs) and sudden cardiac death, especially in young athletes. Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents the best characterized variant of AC, with a peculiar genetic background, established diagnostic criteria and management guidelines; however, the identification of nongenetic causes of the disease, combined with the common demonstration of biventricular and left-dominant forms, has led to coin the term of “arrhythmogenic cardiomyopathy”, to better define the broad spectrum of the disease phenotypic expressions. The genetic basis of AC are pathogenic mutations in genes encoding the cardiac desmosomes, but also non-desmosomal and nongenetic variants were reported in patients with AC, some of which showing overlapping phenotypes with other non-ischemic diseases. The natural history of AC is characterized by VAs and progressive deterioration of cardiac performance. Different phases of the disease are recognized, each characterized by pathological and clinical features. Arrhythmic manifestations are age-related: Ventricular fibrillation and SCD are more frequent in young people, while sustained ventricular tachycardia is more common in the elderly, depending on the different nature of the myocardial lesions. This review aims to address the genetic basis, the clinical course and the phenotypic variants of AC. Full article
(This article belongs to the Special Issue The Metabolic Mechanisms of Cardiomyopathy)
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Open AccessArticle
The Influence of CD28 Gene Polymorphism in Transfusion Reaction after Transfusing Leukoreduced Blood Components
J. Clin. Med. 2020, 9(3), 877; https://doi.org/10.3390/jcm9030877 (registering DOI) - 23 Mar 2020
Viewed by 160
Abstract
CTLA-4 and CD28 belong to co-stimulation molecules, the abnormal expression of which can regulate the T cell activation and then affect the degree of immune response. Moreover, blood transfusion reaction (TR) is a kind of immune reaction. Consequently, the hypothesis of this study [...] Read more.
CTLA-4 and CD28 belong to co-stimulation molecules, the abnormal expression of which can regulate the T cell activation and then affect the degree of immune response. Moreover, blood transfusion reaction (TR) is a kind of immune reaction. Consequently, the hypothesis of this study was that the TR still occurred after transfusing leukoreduced blood components as a result of the sensitivity of immune system, and a small number of immune stimulations were enough to induce an immune response in patients. There were 38 cases and 36 healthy controls included in this study. The selected CD28 gene were sequenced to search single nucleotide polymorphism (SNPs), and the correlation between TR and these SNPs was analyzed. According to our data, only the rs3181097 (promoter, −1059) of CD28 gene polymorphism was associated with TR. The p value of rs3181097 under the co-dominant model was 0.031. GG was used as a reference genotype, the p value of GG vs. AG was 0.010 (OR: 0.210, 95% CI: 0.062–0.712), and GG vs. AG + AA was 0.028 (OR: 0.292, 95% CI: 0.095–0.901). In addition to CTLA-4, CD28 gene was also a crucial SNP in TR, because there was a signification for the haplotype with Grs3181097 (p = 0.015). Consequently, we suggested that the TR was related to CD28 by regulating the degree of immune response. Full article
(This article belongs to the Special Issue New Frontiers in Molecular Hematology)
Open AccessArticle
Damage-Associated Molecular Patterns and Th-Cell-Related Cytokines Released after Progressive Effort
J. Clin. Med. 2020, 9(3), 876; https://doi.org/10.3390/jcm9030876 - 23 Mar 2020
Viewed by 174
Abstract
Inflammation-induced processes commence with the activation of signalling pathways at the cellular level, which mobilize inflammatory cells and stimulate the secretion of chemokines, cytokines, and damage-associated molecular pattern molecules (DAMPs). Physical effort stimulates inflammation, contributing to muscle repair and regeneration. We have examined [...] Read more.
Inflammation-induced processes commence with the activation of signalling pathways at the cellular level, which mobilize inflammatory cells and stimulate the secretion of chemokines, cytokines, and damage-associated molecular pattern molecules (DAMPs). Physical effort stimulates inflammation, contributing to muscle repair and regeneration. We have examined the impact of different protocols of progressive-effort tests on T-cell DAMP levels, extracellular cleavage products (fibronectin and hyaluronan), and Th-cell-related cytokine levels among soccer players. Thirty male soccer players with a median age of 17 (16–22) years performed different defined protocols for progressive exercise until exhaustion: (1) YO-YO intermittent recovery test level 1 (YYRL1, n = 10); (2) maximal multistage 20 m shuttle run (Beep, n = 10); and mechanical treadmill (MT, n = 10); and (3) shuttle-run test (n = 10). Blood samples were taken three times as follows: at baseline, post effort, and in recovery. Significantly higher post-effort concentrations of IL-4, IL-6, IL-10, and IFN-γ were observed in the Beep group, IL-4 in the YYRL1 group, and IL-6 and IFN-γ in the MT group as compared with the baseline values. Recovery values were significantly higher for concentrations of IL-4, IL-10, and IFN-γ in the YYRL1 group, only for IFN-γ in the Beep group, and for IL-6, IL-10, and INF-γ in the MT group as compared with the baseline values. Post-effort concentrations of DEFβ2, Hsp27, Fn, and UA in the Beep group and Hsp27 and HA in the YYRL1 group were significantly higher as compared with the baseline values. It seems the performed efficiency test protocols caused a short-term imbalance in Th1/Th2 cytokine levels without giving common molecular patterns. The rapidity of these changes was apparently related to specific physical movements and the type of running surface. Full article
(This article belongs to the Section Immunology)
Open AccessArticle
Development and Validation of a Quick Sepsis-Related Organ Failure Assessment-Based Machine-Learning Model for Mortality Prediction in Patients with Suspected Infection in the Emergency Department
J. Clin. Med. 2020, 9(3), 875; https://doi.org/10.3390/jcm9030875 - 23 Mar 2020
Viewed by 170
Abstract
The quick sepsis-related organ failure assessment (qSOFA) score has been introduced to predict the likelihood of organ dysfunction in patients with suspected infection. We hypothesized that machine-learning models using qSOFA variables for predicting three-day mortality would provide better accuracy than the qSOFA score [...] Read more.
The quick sepsis-related organ failure assessment (qSOFA) score has been introduced to predict the likelihood of organ dysfunction in patients with suspected infection. We hypothesized that machine-learning models using qSOFA variables for predicting three-day mortality would provide better accuracy than the qSOFA score in the emergency department (ED). Between January 2016 and December 2018, the medical records of patients aged over 18 years with suspected infection were retrospectively obtained from four EDs in Korea. Data from three hospitals (n = 19,353) were used as training-validation datasets and data from one (n = 4234) as the test dataset. Machine-learning algorithms including extreme gradient boosting, light gradient boosting machine, and random forest were used. We assessed the prediction ability of machine-learning models using the area under the receiver operating characteristic (AUROC) curve, and DeLong’s test was used to compare AUROCs between the qSOFA scores and qSOFA-based machine-learning models. A total of 447,926 patients visited EDs during the study period. We analyzed 23,587 patients with suspected infection who were admitted to the EDs. The median age of the patients was 63 years (interquartile range: 43–78 years) and in-hospital mortality was 4.0% (n = 941). For predicting three-day mortality among patients with suspected infection in the ED, the AUROC of the qSOFA-based machine-learning model (0.86 [95% CI 0.85–0.87]) for three -day mortality was higher than that of the qSOFA scores (0.78 [95% CI 0.77–0.79], p < 0.001). For predicting three-day mortality in patients with suspected infection in the ED, the qSOFA-based machine-learning model was found to be superior to the conventional qSOFA scores. Full article
(This article belongs to the Section Emergency Medicine)
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Open AccessArticle
Assessment of the Short-Term Effects after High-Inductive Electromagnetic Stimulation of Pelvic Floor Muscles: A Randomized, Sham-Controlled Study
J. Clin. Med. 2020, 9(3), 874; https://doi.org/10.3390/jcm9030874 (registering DOI) - 23 Mar 2020
Viewed by 162
Abstract
Background: Physiotherapy should be performed by patients with stress or mixed urinary incontinence (SUI and MUI) to increase the strength and endurance of the pelvic floor muscles (PFMs). A method that can positively affect the pelvic floor is stimulation with high-inductive electromagnetic stimulation [...] Read more.
Background: Physiotherapy should be performed by patients with stress or mixed urinary incontinence (SUI and MUI) to increase the strength and endurance of the pelvic floor muscles (PFMs). A method that can positively affect the pelvic floor is stimulation with high-inductive electromagnetic stimulation (HIES). The aim of the study was to evaluate the PFMs after the application of HIES in women with SUI and MUI by using surface electromyography (sEMG). Methods: This was a prospective, randomized, single-blind study with a sham intervention group. The participants were randomly assigned to the HIES group or sham group. The outcomes were features of the bioelectrical PFM activity assessed using sEMG and endovaginal probes. A single-session intervention in the HIES group included 20 min of HIES with an electromagnetic induction intensity of 2.5 T. Results: In the HIES group, there was a statistically significant difference in the PFM sEMG activity during “contractions” (p < 0.001) and “quick flicks” (p = 0.005). In the intergroup comparison, higher PFM sEMG activity after the intervention (“contraction”) was observed in the HIES group than in the sham group (after: p = 0.047; 1 h after: p = 0.017). Conclusions: The assessed HIES method seems effective for SUI and MUI patients in the short term and shows an advantage over the sham intervention in the assessment of PFM contractions. Full article
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Open AccessArticle
Factorial Structure and Validity of Depression (PHQ-9) and Anxiety (GAD-7) Scales after Traumatic Brain Injury
J. Clin. Med. 2020, 9(3), 873; https://doi.org/10.3390/jcm9030873 - 23 Mar 2020
Viewed by 172
Abstract
Background: The dimensionality of depression and anxiety instruments have recently been a source of controversy. Objectives and Design: In a European-wide sample of patients after Traumatic Brain Injury (TBI), we aim to examine the factorial structure, validity, and association of the Patient Health [...] Read more.
Background: The dimensionality of depression and anxiety instruments have recently been a source of controversy. Objectives and Design: In a European-wide sample of patients after Traumatic Brain Injury (TBI), we aim to examine the factorial structure, validity, and association of the Patient Health Questionnaire for depression (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) instruments. This study is based on longitudinal observational data. We conducted analyses of factorial structure and discriminant validity of outcomes six-months after TBI. We also examined the prevalence, co-occurrence, and changes of scores on the PHQ-9 and GAD-7 at 3-, 6-, and 12-month post-TBI assessments. Participants: At six-months post-TBI assessment, 2137 (738 (34.5%) women) participants completed the PHQ-9 and GAD-7 questionnaires. For the longitudinal analysis, we had 1922 participants (672 (35.0%) women). Results: The results of exploratory factor analysis suggested a general latent construct underlying both PHQ-9 and GAD-7 measures. Confirmatory factor analyses showed a slight improvement in the fit indices for the bifactorial model. The Omega hierarchical test clearly differentiated two subfactors of PHQ-9 and GAD-7 items over and above the underlying general factor; however, most of the variance (85.0%) was explained by the general factor and the explained variance of the subfactors was small. The PHQ-9 and GAD-7 performed similarly in detecting post-traumatic stress disorder (PTSD). As defined by conventional cut-offs, depression and anxiety have different prevalence rates in the sample. The scales also differed in their relationships with the short form of health survey (SF-36v2) subscales. The longitudinal analysis showed high stability of depression and anxiety symptoms: 49–67% of the post-TBI patients with comorbid depression and anxiety reported the persistence of the symptoms over time. Discussion: The factorial structure analysis favors a general latent construct underlying both depression and anxiety scales among patients after TBI. We discuss the implications our findings and future research directions. Full article
(This article belongs to the Section Psychiatry)
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Open AccessArticle
Early Post-Stroke Infections Are Associated with an Impaired Function of Neutrophil Granulocytes
J. Clin. Med. 2020, 9(3), 872; https://doi.org/10.3390/jcm9030872 - 23 Mar 2020
Viewed by 182
Abstract
To investigate whether neutrophil granulocytes’ function relates to post-stroke infections and clinical outcome after stroke, we prospectively recruited 95 patients after ischemic stroke and tested them for their microbiocidal neutrophil functions in this exploratory study. Additionally, 24 age-adjusted controls were examined regarding neutrophil [...] Read more.
To investigate whether neutrophil granulocytes’ function relates to post-stroke infections and clinical outcome after stroke, we prospectively recruited 95 patients after ischemic stroke and tested them for their microbiocidal neutrophil functions in this exploratory study. Additionally, 24 age-adjusted controls were examined regarding neutrophil function. Phagocytic capacity and the ability of the neutrophil granulocytes to produce reactive oxygen species (ROS) as well as CD11b and CD16 receptor expression profile were measured by flow cytometry at days 1, 3, 7, and 90 after symptom onset. Primary outcome was the development of an infection within the first week after stroke. Results of neutrophil functional measurements were compared between patients with and without infection as well as between all stroke patients and controls. Further risk factors for the development of infections were summarized in an infection-risk score for the purpose of multivariate statistical analysis. The ROS production in neutrophils after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) was reduced at baseline in patients with post-stroke infections compared to those without (p = 0.013). This difference proved to be independent from the infection-risk score in the binary logistic regression (p = 0.011). Phagocytosis and oxidative bursts were not significantly reduced in the whole stroke patient group compared to controls. Dysfunction of neutrophil granulocytes seems to play a significant role in the development of post-stroke infections. Further studies are warranted to investigate neutrophil granulocytes´ function as a potential biomarker of post-stroke infections. Full article
(This article belongs to the Section Infectious Diseases)
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Open AccessArticle
Artificial Intelligence-Based Diagnosis of Cardiac and Related Diseases
J. Clin. Med. 2020, 9(3), 871; https://doi.org/10.3390/jcm9030871 (registering DOI) - 23 Mar 2020
Viewed by 225
Abstract
Automatic chest anatomy segmentation plays a key role in computer-aided disease diagnosis, such as for cardiomegaly, pleural effusion, emphysema, and pneumothorax. Among these diseases, cardiomegaly is considered a perilous disease, involving a high risk of sudden cardiac death. It can be diagnosed early [...] Read more.
Automatic chest anatomy segmentation plays a key role in computer-aided disease diagnosis, such as for cardiomegaly, pleural effusion, emphysema, and pneumothorax. Among these diseases, cardiomegaly is considered a perilous disease, involving a high risk of sudden cardiac death. It can be diagnosed early by an expert medical practitioner using a chest X-Ray (CXR) analysis. The cardiothoracic ratio (CTR) and transverse cardiac diameter (TCD) are the clinical criteria used to estimate the heart size for diagnosing cardiomegaly. Manual estimation of CTR and other diseases is a time-consuming process and requires significant work by the medical expert. Cardiomegaly and related diseases can be automatically estimated by accurate anatomical semantic segmentation of CXRs using artificial intelligence. Automatic segmentation of the lungs and heart from the CXRs is considered an intensive task owing to inferior quality images and intensity variations using nonideal imaging conditions. Although there are a few deep learning-based techniques for chest anatomy segmentation, most of them only consider single class lung segmentation with deep complex architectures that require a lot of trainable parameters. To address these issues, this study presents two multiclass residual mesh-based CXR segmentation networks, X-RayNet-1 and X-RayNet-2, which are specifically designed to provide fine segmentation performance with a few trainable parameters compared to conventional deep learning schemes. The proposed methods utilize semantic segmentation to support the diagnostic procedure of related diseases. To evaluate X-RayNet-1 and X-RayNet-2, experiments were performed with a publicly available Japanese Society of Radiological Technology (JSRT) dataset for multiclass segmentation of the lungs, heart, and clavicle bones; two other publicly available datasets, Montgomery County (MC) and Shenzhen X-Ray sets (SC), were evaluated for lung segmentation. The experimental results showed that X-RayNet-1 achieved fine performance for all datasets and X-RayNet-2 achieved competitive performance with a 75% parameter reduction. Full article
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Open AccessArticle
Emergent Properties of the HNF4α-PPARγ Network May Drive Consequent Phenotypic Plasticity in NAFLD
J. Clin. Med. 2020, 9(3), 870; https://doi.org/10.3390/jcm9030870 (registering DOI) - 22 Mar 2020
Viewed by 442
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in adults and children. It is characterized by excessive accumulation of lipids in the hepatocytes of patients without any excess alcohol intake. With a global presence of 24% and [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in adults and children. It is characterized by excessive accumulation of lipids in the hepatocytes of patients without any excess alcohol intake. With a global presence of 24% and limited therapeutic options, the disease burden of NAFLD is increasing. Thus, it becomes imperative to attempt to understand the dynamics of disease progression at a systems-level. Here, we decoded the emergent dynamics of underlying gene regulatory networks that were identified to drive the initiation and the progression of NAFLD. We developed a mathematical model to elucidate the dynamics of the HNF4α-PPARγ gene regulatory network. Our simulations reveal that this network can enable multiple co-existing phenotypes under certain biological conditions: an adipocyte, a hepatocyte, and a “hybrid” adipocyte-like state of the hepatocyte. These phenotypes may also switch among each other, thus enabling phenotypic plasticity and consequently leading to simultaneous deregulation of the levels of molecules that maintain a hepatic identity and/or facilitate a partial or complete acquisition of adipocytic traits. These predicted trends are supported by the analysis of clinical data, further substantiating the putative role of phenotypic plasticity in driving NAFLD. Our results unravel how the emergent dynamics of underlying regulatory networks can promote phenotypic plasticity, thereby propelling the clinically observed changes in gene expression often associated with NAFLD. Full article
(This article belongs to the Special Issue Non-Alcoholic Steatohepatitis (NASH))
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Open AccessArticle
Knowledge of Rare Respiratory Diseases among Paediatricians and Medical School Students
J. Clin. Med. 2020, 9(3), 869; https://doi.org/10.3390/jcm9030869 - 22 Mar 2020
Viewed by 217
Abstract
Alpha-1-antitrypsin deficiency (AATD) and primary ciliary dyskinesia (PCD) are underdiagnosed rare diseases showing a median diagnostic delay of five to ten years, which has negative effects on patient prognosis. Lack of awareness and education among healthcare professionals involved in the management of these [...] Read more.
Alpha-1-antitrypsin deficiency (AATD) and primary ciliary dyskinesia (PCD) are underdiagnosed rare diseases showing a median diagnostic delay of five to ten years, which has negative effects on patient prognosis. Lack of awareness and education among healthcare professionals involved in the management of these patients have been suggested as possible causes. Our aim was to assess knowledge of these diseases among paediatricians and medical school students to determine which knowledge areas are most deficient. A survey was designed with questions testing fundamental aspects of the diagnosis and treatment of AATD and PCD. A score equal to or greater than 50% of the maximum score was set as the level necessary to ensure a good knowledge of both diseases. Our results indicate a profound lack of knowledge of rare respiratory diseases among paediatric professionals and medical students, suggesting that it is necessary to increase rare respiratory diseases training among all physicians responsible for suspecting and diagnosing them; this will allow early diagnosis and the setup of preventive measures and appropriate early-stage treatment. The first step in closing this knowledge gap could be to include relevant material in the medical syllabus. Full article
(This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem)
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Open AccessArticle
Effect of Botulinum Toxin A on Scar Healing after Thyroidectomy: A Prospective Double-blind Randomized Controlled Trial
J. Clin. Med. 2020, 9(3), 868; https://doi.org/10.3390/jcm9030868 - 21 Mar 2020
Viewed by 241
Abstract
The persistence of neck scarring is a common concern among patients undergoing thyroidectomy. Botulinum toxin A (BTA (Botox)) has been shown to suppress scar enlargement at the incision site. The objective of this study was to evaluate the effect of intraoperative Botox administration [...] Read more.
The persistence of neck scarring is a common concern among patients undergoing thyroidectomy. Botulinum toxin A (BTA (Botox)) has been shown to suppress scar enlargement at the incision site. The objective of this study was to evaluate the effect of intraoperative Botox administration on neck scarring after thyroidectomy. A prospective double-blind randomized clinical trial was performed in patients undergoing conventional thyroidectomy. Forty patients were randomly allocated to a Botox or a control group (both, n = 20). The wound was closed after injection into the platysma muscle of 50 U of Botox diluted in 1 mL of normal saline or 1 mL of saline alone. Skin scars were assessed using the modified Stony Brook Scar Evaluation Scale (SBSES) and Manchester Scar Scale (MSS) at 1, 12, and 24 weeks postoperatively. The SBSES and MSS scores of the Botox group were significantly better than those of the control group (p = 0.034 and p = 0.039). At 24 weeks postoperatively, the SBSES and MSS scores were significantly better in the Botox group (p = 0.006 and p = 0.030). BTA injected into the incision site can suppress postoperative scar formation and thereby improve the cosmetic outcome. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessArticle
Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders
J. Clin. Med. 2020, 9(3), 867; https://doi.org/10.3390/jcm9030867 - 21 Mar 2020
Viewed by 211
Abstract
Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs. Methods: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays. Results: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia. Conclusion: The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results. Full article
(This article belongs to the Special Issue Frontiers in Oral Cancer—Basic and Clinical Sciences)
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Open AccessReview
Endoscopic Ultrasound-Guided Treatments for Non-Variceal Upper GI Bleeding: A Review of the Literature
J. Clin. Med. 2020, 9(3), 866; https://doi.org/10.3390/jcm9030866 - 21 Mar 2020
Viewed by 165
Abstract
Endoscopic injection of glues, clotting factors, or sclerosing agents is a well-known therapy for the treatment of non-variceal upper gastrointestinal bleeding (NVUGIB), but less is known about endoscopic ultrasound (EUS)-guided treatments. In this setting, literature data are scarce, and no randomized controlled trials [...] Read more.
Endoscopic injection of glues, clotting factors, or sclerosing agents is a well-known therapy for the treatment of non-variceal upper gastrointestinal bleeding (NVUGIB), but less is known about endoscopic ultrasound (EUS)-guided treatments. In this setting, literature data are scarce, and no randomized controlled trials are available. We performed a review of the existing literature in order to evaluate the role of EUS-guided therapies in the management of NVUGIB. The most common treated lesions were Dieulafoy’s lesions, pancreatic pseudoaneurysms, and gastrointestinal stromal tumors (GISTs). Mostly, the treatments were performed as a salvage option after failure of conventional endoscopic hemostatic attempts, showing good efficacy and a good safety profile, also documented by Doppler monitoring of treated lesions. EUS-guided therapies may be an effective option in the treatment of refractory NVUGIB, thus avoiding radiological or surgical management. Nevertheless, available literature still lacks robust data. Full article
(This article belongs to the Special Issue New Trends and Advances in Non-Variceal Gastrointestinal Bleeding)
Open AccessReview
Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients
J. Clin. Med. 2020, 9(3), 865; https://doi.org/10.3390/jcm9030865 - 21 Mar 2020
Viewed by 282
Abstract
Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections [...] Read more.
Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections in these vulnerable hosts is of utmost importance and a key “safety net” in stem cell transplantation. In this review, we provide updates on the prevention and management of CMV infection; invasive fungal infections; bacterial infections; Clostridium difficile infection; and EBV, HHV-6, adenovirus and BK infections. We discuss novel drugs, such as letermovir, isavuconazole, meropenem-vaborbactam and bezlotoxumab; weigh the pros and cons of using fluoroquinolone prophylaxis during neutropenia after stem cell transplantation; and provide updates on important viral infections after hematopoietic stem cell transplant (HSCT). Optimizing the prevention and management of infectious diseases by using the best available evidence will contribute to better outcomes for stem cell transplant recipients, and provide the best possible “safety net” for these immunocompromised hosts. Full article
(This article belongs to the Special Issue Hematopoietic Cell Transplantation and Cellular Therapy: A New Era)
Open AccessArticle
Clinical Characteristics and Outcome of Patients with Infective Endocarditis Diagnosed in a Department of Internal Medicine
J. Clin. Med. 2020, 9(3), 864; https://doi.org/10.3390/jcm9030864 - 21 Mar 2020
Viewed by 171
Abstract
Clinical manifestations of infective endocarditis (IE) can be highly non-specific. Our objective was to describe the clinical characteristics of patients initially referred to a department of internal medicine for a diagnostic work-up, and eventually diagnosed with IE. We retrospectively retrieved adult patients admitted [...] Read more.
Clinical manifestations of infective endocarditis (IE) can be highly non-specific. Our objective was to describe the clinical characteristics of patients initially referred to a department of internal medicine for a diagnostic work-up, and eventually diagnosed with IE. We retrospectively retrieved adult patients admitted to the department of internal medicine at Lille University Hospital between 2004 and 2015 who fulfilled Duke Classification criteria for definite IE. Thirty-five patients were included. The most frequently involved bacteria were non-hemolytic streptococci. Most patients presented with various systemic, cardiac, embolic, rheumatic, and immunological findings, with no sign or symptom displaying high sensitivity. The first transthoracic echocardiogram was negative in 42% of patients. Furthermore, definite diagnosis required performing at least 2 transesophageal examinations in 24% of patients. We observed a trend towards decreased survival in the subgroup of patients in whom the delay between onset of symptoms and diagnosis was >30 days. In conclusion, patients who are initially referred to internal medicine for a diagnosis work-up and who are ultimately diagnosed with IE have non-specific symptoms and a high percentage of initial normal echocardiography. Those patients require prolonged echocardiographic monitoring as a prolonged delay in diagnosis is associated with poorer outcomes such as death. Full article
(This article belongs to the Special Issue Infective Endocarditis)
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