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Volume 8, September

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J. Clin. Med., Volume 8, Issue 10 (October 2019)

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Cover Story (view full-size image) We investigated treatment with a virus-derived immune modulating serine protease inhibitor [...] Read more.
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Open AccessReview
Comparison of Hemodynamic Factors Predicting Prognosis in Heart Failure: A Systematic Review
J. Clin. Med. 2019, 8(10), 1757; https://doi.org/10.3390/jcm8101757 (registering DOI) - 22 Oct 2019
Abstract
Objectives: We systematically reviewed the literature to address the question of which of the three hemodynamic factors predicts prognosis best in heart failure patients when directly compared to each other: cardiac output, preload or afterload. Methods: Prognostic studies in heart failure (HF) were [...] Read more.
Objectives: We systematically reviewed the literature to address the question of which of the three hemodynamic factors predicts prognosis best in heart failure patients when directly compared to each other: cardiac output, preload or afterload. Methods: Prognostic studies in heart failure (HF) were searched that included at least two of the three hemodynamic variables: (1) cardiac output or cardiac index (CI), (2) preload represented by pulmonary capillary wedge pressure (PCWP) and (3) afterload simplified to systolic blood pressure (SBP). Critical appraisal was done according to the QUIPS format for prognostic studies. The main endpoint was all-cause mortality, which could be combined with other endpoints. We report the number of studies in which CI, PCWP and SBP remained significant prognostic predictors in multivariate analysis. We also assessed whether hemodynamic predictors of prognosis varied in four different HF-populations. Results: Included were 18 studies containing a multivariate analysis. PCWP was an independent predictor of prognosis in 10 of 18 studies, SBP in 3 of 14 studies and CI in none of 18 studies. Results were not specific for any of the HF-populations. Conclusions: A higher PCWP and lower SBP are independent predictors of poor prognosis in HF. In spite of the frequently used concept behind HF, this review demonstrates that CI is not an independent predictor of prognosis in HF. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR): A Comparison Study between Ironman Athletes, Age Matched Controls and A General Community Cohort
J. Clin. Med. 2019, 8(10), 1756; https://doi.org/10.3390/jcm8101756 (registering DOI) - 22 Oct 2019
Abstract
Background: During exercise there is a proportionally lower rise in systemic and pulmonary pressures compared to cardiac output due to reduced vascular resistance. Invasive exercise data suggest that systemic vascular resistance reduces more than pulmonary vascular resistance. The aim of this study was [...] Read more.
Background: During exercise there is a proportionally lower rise in systemic and pulmonary pressures compared to cardiac output due to reduced vascular resistance. Invasive exercise data suggest that systemic vascular resistance reduces more than pulmonary vascular resistance. The aim of this study was the non-invasive assessment of exercise hemodynamics in ironman athletes, compared with an age matched control group and a larger general community cohort. Methods: 20 ironman athletes (40 ± 11 years, 17 male) were compared with 20 age matched non-athlete controls (43 ± 7 years, 10 male) and a general community cohort of 230 non-athletes individuals (66 ± 11 years, 155 male), at rest and after maximal-symptom limited treadmill exercise stress echocardiography. Left heart parameters (mitral E-wave, e’-wave and E/e’) and right heart parameters (tricuspid regurgitation maximum velocity and right ventricular systolic pressure), were used to calculate the echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) value of the three groups. Results: Athletes exercised for 12.2 ± 0.53 minutes, age matched controls for 10.1 ± 2.8 minutes and general community cohort for 8.3 ± 2.6 minutes. Mitral E/e’ rose slightly for athletes (0.9 ± 1.8), age matched controls (0.6 ± 3.0) and non-athletes (0.4 ± 3.2). Right ventricular systolic pressure increased significantly more in athletes than in both non-athlete cohorts (35.6 ± 17 mmHg vs. 20.4±10.8mmHg and 18 ± 9.6 mmHg). The marker of trans-pulmonary gradient, ePLAR, rose significantly more in athletes than in both non-athlete groups (0.15 ± 0.1 m/s vs. 0.07 ± 0.1 m/s). Conclusions: Pulmonary pressures increased proportionally four-fold compared with systemic pressures in ironman athletes. This increase in pulmonary vascular resistance corresponded with a two-fold increase in ePLAR. These changes were exaggerated compared with both non-ironman cohorts. Such changes have been previously suggested to lead to right ventricle dysfunction, arrhythmias and sudden cardiac death. Full article
Open AccessArticle
Nosocomial Vs. Community-Acquired Infective Endocarditis in Spain: Location, Trends, Clinical Presentation, Etiology, and Survival in the 21st Century
J. Clin. Med. 2019, 8(10), 1755; https://doi.org/10.3390/jcm8101755 (registering DOI) - 22 Oct 2019
Abstract
Major changes have occurred in the epidemiology and etiology of infective endocarditis (IE). Nevertheless, the differences between nosocomial infective endocarditis (NIE) and community-acquired infective endocarditis (CIE) have not been addressed in a population-based study. We conducted a retrospective, nationwide, temporal trend study from [...] Read more.
Major changes have occurred in the epidemiology and etiology of infective endocarditis (IE). Nevertheless, the differences between nosocomial infective endocarditis (NIE) and community-acquired infective endocarditis (CIE) have not been addressed in a population-based study. We conducted a retrospective, nationwide, temporal trend study from 1997 to 2014 analyzing the epidemiology, clinical, geographical, meteorological characteristics of patients diagnosed with IE in Spain, to distinguish NIE from CIE. Among 25,952 patients with IE (62.2 ± 18·6 years; 65.9% men), 45.9% had NIE. The incidence of IE increased from 2.83 to 3.73 due to the NIE incidence increment with a decline in CIE. Patients with NIE were older (63.8 years vs. 60.8 years, p < 0·001), presented a higher Charlson index (1.22 vs. 1.03, p < 0.001), a greater history of implanted cardiac devices (8.7% vs. 4.6%, p < 0.001), and higher mortality (31.5% vs. 21.7%, p < 0.001). The most frequent microorganism for both NIE and CIE was Staphylococcus (p < 0.001), and the North reported a higher incidence (p < 0.001). Risk factors of mortality for NIE were age, Charlson index, hemodialysis, shock, heart failure, and stroke. Risk factors for CIE included female sex, renal disease, and cardiac-device carriers. The etiology of IE shifted from community origins to mostly nosocomial-associated infections. Higher morbidity, mortality, and poorer outcomes are associated with NIE. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessReview
Obstructive Sleep Apnea: Emerging Treatments Targeting the Genioglossus Muscle
J. Clin. Med. 2019, 8(10), 1754; https://doi.org/10.3390/jcm8101754 (registering DOI) - 22 Oct 2019
Abstract
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus [...] Read more.
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus (GG) is the main upper airway dilator muscle. Currently, continuous positive airway pressure is the first-line treatment for OSA. Nevertheless, problems related to poor adherence have been described in some groups of patients. In recent years, new OSA treatment strategies have been developed to improve GG function. (A) Hypoglossal nerve electrical stimulation leads to significant improvements in objective (apnea-hypopnea index, or AHI) and subjective measurements of OSA severity, but its invasive nature limits its application. (B) A recently introduced combination of drugs administered orally before bedtime reduces AHI and improves the responsiveness of the GG. (C) Finally, myofunctional therapy also decreases AHI, and it might be considered in combination with other treatments. Our objective is to review these therapies in order to advance current understanding of the prospects for alternative OSA treatments. Full article
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Open AccessReview
Oral–Gut Microbiota and Arthritis: Is There an Evidence-Based Axis?
J. Clin. Med. 2019, 8(10), 1753; https://doi.org/10.3390/jcm8101753 (registering DOI) - 22 Oct 2019
Abstract
The gut microbiome appears to be a significant contributor to musculoskeletal health and disease. Recently, it has been found that oral microbiota are involved in arthritis pathogenesis. Microbiome composition and its functional implications have been associated with the prevention of bone loss and/or [...] Read more.
The gut microbiome appears to be a significant contributor to musculoskeletal health and disease. Recently, it has been found that oral microbiota are involved in arthritis pathogenesis. Microbiome composition and its functional implications have been associated with the prevention of bone loss and/or reducing fracture risk. The link between gut–oral microbiota and joint inflammation in animal models of arthritis has been established, and it is now receiving increasing attention in human studies. Recent papers have demonstrated substantial alterations in the gut and oral microbiota in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). These alterations resemble those established in systemic inflammatory conditions (inflammatory bowel disease, spondyloarthritides, and psoriasis), which include decreased microbial diversity and a disturbance of immunoregulatory properties. An association between abundance of oral Porphyromonas gingivalis and intestinal Prevotella copri in RA patients compared to healthy controls has been clearly demonstrated. These new findings open important future horizons both for understanding disease pathophysiology and for developing novel biomarkers and treatment strategies. The changes and decreased diversity of oral and gut microbiota seem to play an important role in the etiopathogenesis of RA and OA. However, specific microbial clusters and biomarkers belonging to oral and gut microbiota need to be further investigated to highlight the mechanisms related to alterations in bones and joints inflammatory pathway. Full article
(This article belongs to the Special Issue Skin-Gut-Breast Microbiota Axes)
Open AccessArticle
A TUG Value Longer Than 11 s Predicts Fall Risk at 6-Month in Individuals with COPD
J. Clin. Med. 2019, 8(10), 1752; https://doi.org/10.3390/jcm8101752 (registering DOI) - 22 Oct 2019
Abstract
Risk of a fall is increased in individuals with chronic obstructive pulmonary disease (COPD), and is usually evaluated using the Berg Balance Scale (BBS), but this is difficult to perform in everyday clinical practice. We aimed to prospectively predict short-term fall recurrence in [...] Read more.
Risk of a fall is increased in individuals with chronic obstructive pulmonary disease (COPD), and is usually evaluated using the Berg Balance Scale (BBS), but this is difficult to perform in everyday clinical practice. We aimed to prospectively predict short-term fall recurrence in COPD patients using a predetermined cut-off value of the Timed Up and Go test (TUG). In stable COPD patients, we collected self-reported records of the number of falls in the previous year, and measured TUG and BBS scores for each individual. Records of fall recurrence were obtained prospectively at 6-months after the initial evaluation. Among the 50 patients recruited, 23 (46%) had at least one fall during the past year. The optimal diagnosis value for the TUG to detect a fall was 10.9 s with a sensitivity of 100% and a specificity of 97%. A cut-off of 11 s predicted fall recurrence with high sensitivity and specificity (93% and 74%, respectively). The TUG as well as the BBS score detected fallers, and a cut-off value of 11 s predicted fall recurrence. TUG could be easily incorporated into the scheduled functional evaluations of COPD patients, could predict the risk of a fall and when appropriate, could guide specific balance training exercises to prevent fall. Full article
(This article belongs to the Section Pulmonology)
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Open AccessArticle
GSKIP-Mediated Anchoring Increases Phosphorylation of Tau by PKA but Not by GSK3beta via cAMP/PKA/GSKIP/GSK3/Tau Axis Signaling in Cerebrospinal Fluid and iPS Cells in Alzheimer Disease
J. Clin. Med. 2019, 8(10), 1751; https://doi.org/10.3390/jcm8101751 - 21 Oct 2019
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Abstract
Based on the protein kinase A (PKA)/GSK3β interaction protein (GSKIP)/glycogen synthase kinase 3β (GSK3β) axis, we hypothesized that these might play a role in Tau phosphorylation. Here, we report that the phosphorylation of Tau Ser409 in SHSY5Y cells was increased by overexpression of [...] Read more.
Based on the protein kinase A (PKA)/GSK3β interaction protein (GSKIP)/glycogen synthase kinase 3β (GSK3β) axis, we hypothesized that these might play a role in Tau phosphorylation. Here, we report that the phosphorylation of Tau Ser409 in SHSY5Y cells was increased by overexpression of GSKIP WT more than by PKA- and GSK3β-binding defective mutants (V41/L45 and L130, respectively). We conducted in vitro assays of various kinase combinations to show that a combination of GSK3β with PKA but not Ca2+/calmodulin-dependent protein kinase II (CaMK II) might provide a conformational shelter to harbor Tau Ser409. Cerebrospinal fluid (CSF) was evaluated to extend the clinical significance of Tau phosphorylation status in Alzheimer’s disease (AD), neurological disorders (NAD), and mild cognitive impairment (MCI). We found higher levels of different PKA–Tau phosphorylation sites (Ser214, Ser262, and Ser409) in AD than in NAD, MCI, and normal groups. Moreover, we used the CRISPR/Cas9 system to produce amyloid precursor protein (APPWT/D678H) isogenic mutants. These results demonstrated an enhanced level of phosphorylation by PKA but not by the control. This study is the first to demonstrate a transient increase in phosphor-Tau caused by PKA, but not GSK3β, in the CSF and induced pluripotent stem cells (iPSCs) of AD, implying that both GSKIP and GSK3β function as anchoring proteins to strengthen the cAMP/PKA/Tau axis signaling during AD pathogenesis. Full article
(This article belongs to the Special Issue Energetic Metabolism Impairment in Brain Dysfunction)
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Open AccessReview
Neonate Bloodstream Infections in Organization for Economic Cooperation and Development Countries: An Update on Epidemiology and Prevention
J. Clin. Med. 2019, 8(10), 1750; https://doi.org/10.3390/jcm8101750 - 21 Oct 2019
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Abstract
The term neonatal sepsis is used to describe a generalized bloodstream infection of bacterial, viral, or fungal origin which is associated with hemodynamic changes and other clinical symptoms and signs, however, there is no unified definition. There are no basic criteria regarding differentiation [...] Read more.
The term neonatal sepsis is used to describe a generalized bloodstream infection of bacterial, viral, or fungal origin which is associated with hemodynamic changes and other clinical symptoms and signs, however, there is no unified definition. There are no basic criteria regarding differentiation of early-onset sepsis (EOS) versus late-onset sepsis (LOS). Stratification used in studies on neonatal sepsis also rarely includes the general condition of the newborn according to unambiguous assessment at birth, which hampers the establishment of a clear, uniform epidemiological description of neonatal sepsis. We aim to review the published data about the epidemiology and microbiology of sepsis in Organization for Economic Cooperation and Development (OECD) countries. Data was also collected on sepsis prevention programs that can be implemented in neonatal units. The outcomes of interest were incidence or incidence density of EOS and LOS, microbiology of EOS and LOS, and data on the methodology of the research, in particular the criteria for inclusion and exclusion of newborns from the study. Pubmed, EMBASE, LILACS Embase, Scopus, and Google Scholar were used. For the preselection step, inclusion criteria included: “bloodstream infection” or “neonatal sepsis” (MesH), “very low birth weight”, and “country” full-text studies, human, and English language. Exclusion criteria included: studies published in languages other than English and studies available only as an abstracts. For proper selection, inclusion criteria included: information about epidemiology or microbiology bloodstream infection (BSI), study population and case definitions, exclusion criteria, narrative reviews, commentaries, case studies, pilot studies, study protocols, pediatric studies, and only clinical data (without microbiology or epidemiology) or studies with only one etiological factor analysis. The data review indicated the lack of an unequivocal, unified definition and no unambiguous basic criteria with regard to differentiation of EOS versus LOS. Among infants <1500 g, studies reported an EOS rate from 7% to 2%. For studies using other definitions (mostly all inborn babies), the rate of EOS ranged from 1% to 3%. The LOS incidences were much more varied among countries; the highest rates were in the multicenter studies focused on very low birth weight (VLBW) infants. The main pathogens in EOS are GBS and Gram-negative bacteria in LOS. Our review data shows that LOS microbiology is very diverse and that Gram-positive cocci, especially staphylococci, predominate versus Gram-negative rods. Unfortunately, the lack of uniform, international prevention programs results in high newborn morbidity and insufficient postnatal prevention of late-onset infections. Full article
(This article belongs to the Section Epidemiology & Public Health)
Open AccessArticle
Preoperative Clinical and Computed Tomography (CT)-Based Nomogram to Predict Oncologic Outcomes in Patients with Pancreatic Head Cancer Resected with Curative Intent: A Retrospective Study
J. Clin. Med. 2019, 8(10), 1749; https://doi.org/10.3390/jcm8101749 - 21 Oct 2019
Viewed by 92
Abstract
Background: Currently, proposed nomograms are mainly based on post-operative histopathology. The purpose of this study was to identify preoperative computed tomography (CT) and clinical information that allow prediction of disease-free (DFS) and overall survival (OS) of patients surgically treated for pancreatic head cancer. [...] Read more.
Background: Currently, proposed nomograms are mainly based on post-operative histopathology. The purpose of this study was to identify preoperative computed tomography (CT) and clinical information that allow prediction of disease-free (DFS) and overall survival (OS) of patients surgically treated for pancreatic head cancer. Methods: A total of 136 patients who underwent curative-intent surgery were retrospectively reviewed. Based on results from multivariate Cox regression analysis, a prediction model was constructed with preoperative CT features and clinical information. Overall performance of the nomogram was calculated by Harrell’s C-index. Results: Symptoms at diagnosis, preoperative serum CA 19-9 ≥ 34 U/mL, and four imaging features (necrosis (DFS, P = 0.066; OS, P = 0.002), possible venous invasion (DFS, P = 0.150, OS, P = 0.055), suspected metastatic regional lymph node (DFS, P = 0.001; OS, P = 0.099), and associated pancreatitis or pseudocyst (DFS, P = 0.013; OS, P = 0.041)) were included to build the nomogram. The c-statistics for the discrimination power of the proposed nomogram was 0.6496 for DFS and 0.6746 for OS. Conclusion: A nomogram derived from preoperative CT and clinical information could estimate the risk of recurrence and all-cause death after curative-intent surgery for radiologically resectable pancreatic head cancer. Full article
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Open AccessEditorial
Small Bowel—Key Player in Health and Disease
J. Clin. Med. 2019, 8(10), 1748; https://doi.org/10.3390/jcm8101748 - 21 Oct 2019
Viewed by 127
Abstract
Over the last two decades, remarkable progress has been made in understanding the etiology and pathophysiology of diseases [...] Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Small Bowel Disorders)
Open AccessReview
Oral Anticoagulant Therapy—When Art Meets Science
J. Clin. Med. 2019, 8(10), 1747; https://doi.org/10.3390/jcm8101747 - 21 Oct 2019
Viewed by 116
Abstract
Anticoagulant treatment is extremely important and frequently encountered in the therapy of various cardiovascular diseases. Vitamin K antagonists (VKA) are in use for the prevention and treatment of arterial and venous thromboembolism, despite the introduction of new direct-acting oral anticoagulants (NOAC). The VKA [...] Read more.
Anticoagulant treatment is extremely important and frequently encountered in the therapy of various cardiovascular diseases. Vitamin K antagonists (VKA) are in use for the prevention and treatment of arterial and venous thromboembolism, despite the introduction of new direct-acting oral anticoagulants (NOAC). The VKA still have the clear recommendation in patients with a mechanical prosthetic heart valve replacement or moderate to severe mitral stenosis of the rheumatic origin, in deep vein thrombosis associated with congenital thrombophilia, and in cases where NOAC are prohibited by social condition (financial reason) or by comorbidities (extreme weight, severe renal or liver disease). VKA dosing required to reach the targeted therapeutic range varies largely between patients (inter-individual variability). This inter-individual variability depends on multiple environmental factors such as age, mass, diet, etc. but it is also influenced by genetic determinism. About 30 genes implicated in the metabolism coumarins derivatives were identified, the most important being CYP2C9 and VKORC, each with several polymorphisms. Herein, we review the data regarding genetic alterations in general and specific populations, highlight the diagnosis options in particular cases presenting with genetic alteration causing higher sensitivity and/or resistance to VKA therapy and underline the utility of NOAC in solving such rare and difficult problems. Full article
(This article belongs to the Section Cardiology)
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Open AccessReview
The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure
J. Clin. Med. 2019, 8(10), 1746; https://doi.org/10.3390/jcm8101746 - 21 Oct 2019
Viewed by 90
Abstract
Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are [...] Read more.
Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are synthesized in response to atrial cardiomyocyte stretch, increase natriuresis, diuresis, and vascular permeability through binding of the second intracellular messenger’s guanosine 3′,5′-cyclic monophosphate (cGMP) to specific receptors. During heart failure (HF), the beneficial effects of the enhanced cardiac hormones secretion are reduced, in connection with renal resistance to NP. In addition, there is a BNP paradox characterized by a physiological inefficiency of the BNP forms assayed by current methods. In this context, it appears interesting to improve the efficiency of the cardiac natriuretic system by inhibiting cyclic nucleotide phosphodiesterases, responsible for the degradation of cGMP. Recent data support such a therapeutic approach which can improve the quality of life and the prognosis of patients with HF. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Home-Based Exergaming on Preschoolers’ Energy Expenditure, Cardiovascular Fitness, Body Mass Index and Cognitive Flexibility: A Randomized Controlled Trial
J. Clin. Med. 2019, 8(10), 1745; https://doi.org/10.3390/jcm8101745 - 21 Oct 2019
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Abstract
Purpose: The effects of exergaming-based physical activity (PA) interventions on preschoolers’ health outcomes and cognition remain largely unexplored. Therefore, we conducted a randomized controlled trial to discern the effectiveness of a home-based educational exergaming intervention on preschoolers’ energy expenditure, fitness, body mass index, [...] Read more.
Purpose: The effects of exergaming-based physical activity (PA) interventions on preschoolers’ health outcomes and cognition remain largely unexplored. Therefore, we conducted a randomized controlled trial to discern the effectiveness of a home-based educational exergaming intervention on preschoolers’ energy expenditure, fitness, body mass index, and cognition. Methods: Participants were 32 preschoolers (16 girls; 59.4% Asian; Mage = 4.72, SD = ±0.73) recruited from the Twin Cities area in Minnesota. During baseline testing, we measured preschooler’s daily energy expenditure (EE), cardiovascular fitness, body mass index, and cognitive flexibility using validated instruments. Participants were then randomly assigned to one of two conditions: (1) the exergaming intervention condition; or (2) control condition. The intervention program requested children participate in home-based educational exergaming using the LeapTV gaming console for at least 30 min/session 5 times/week. The control condition asked children to maintain regular PA patterns without any exergaming gameplay. Each condition lasted 12 weeks. We conducted identical outcome assessments for all children at baseline and post-intervention. Results: Analysis of covariance with repeated measures yielded significant time x group interaction effects for cognitive flexibility, Wilks’ Lambda = 0.81, F(1, 29) = 6.98, p = 0.01, η2 = 0.19, suggesting children in the exergaming group demonstrated significantly greater increases in cognitive flexibility as compared to those in the control group over time. There were no significant differences for time x group changes between the two groups for EE, Wilks’ Lambda = 0.92, F(1, 29) = 2.29, p = 0.14, η2 = 0.08; cardiovascular fitness, Wilks’ Lambda = 0.96, F(1, 29) = 1.07, p = 0.31, η2 = 0.04; and BMI, Wilks’ Lambda = 0.99, F(1, 29) = 0.05, p = 0.82, η2 = 0.01. However, our data did suggest a marginal effect of time for EE, Wilks’ Lambda = 0.89, F(1, 29) = 3.26, p = 0.08, η2 = 0.08, indicating that children’s daily EE increased from baseline to post-intervention. Conclusions: Home-based educational exergaming may positively impact cognitive flexibility in preschoolers. Studies with larger sample sizes in multiple geographic locations are needed, with our study suggesting a longer intervention period might also be warranted. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessArticle
SOX2 Expression Is an Independent Predictor of Oral Cancer Progression
J. Clin. Med. 2019, 8(10), 1744; https://doi.org/10.3390/jcm8101744 - 21 Oct 2019
Viewed by 106
Abstract
Potentially malignant oral lesions, mainly leukoplakia, are common. Malignant transformation varies widely, even in the absence of histological features such as dysplasia. Hence, there is a need for novel biomarker-based systems to more accurately predict the risk of cancer progression. The pluripotency transcription [...] Read more.
Potentially malignant oral lesions, mainly leukoplakia, are common. Malignant transformation varies widely, even in the absence of histological features such as dysplasia. Hence, there is a need for novel biomarker-based systems to more accurately predict the risk of cancer progression. The pluripotency transcription factor SOX2 is frequently overexpressed in cancers, including oral squamous cell carcinoma (OSCC), thereby providing a link between malignancy and stemness. This study investigates the clinical relevance of SOX2 protein expression in early stages of oral carcinogenesis as a cancer risk biomarker, and also its impact on prognosis and disease outcome at late stages of OSCC progression. SOX2 expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and in 125 patients with OSCC, and correlated with clinicopathological data and outcomes. Nuclear SOX2 expression was detected in four (7%) cases of oral epithelial dysplasia, using a cut-off of 10% stained nuclei, and in 16 (29%) cases when any positive nuclei was evaluated. Univariate analysis showed that SOX2 expression and histopathological grading were significantly associated with oral cancer risk; and both were found to be significant independent predictors in the multivariate analysis. Nuclear SOX2 expression was also found in 49 (39%) OSCC cases, was more frequent in early tumor stages and N0 cases, and was associated with a better survival. In conclusion, SOX2 expression emerges as an independent predictor of oral cancer risk in patients with oral leukoplakia. These findings underscore the relevant role of SOX2 in early oral tumorigenesis rather than in tumor progression. Full article
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Open AccessArticle
Probiotics in Adolescent Prediabetes: A Pilot RCT on Glycemic Control and Intestinal Bacteriome
J. Clin. Med. 2019, 8(10), 1743; https://doi.org/10.3390/jcm8101743 - 21 Oct 2019
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Abstract
Dysbiosis of intestinal ecology could be implicated in prediabetes. The aim of this pilot randomized controlled trial (RCT) was to collect preliminary data on the effects of probiotic supplementation (Vivomixx©) on markers of glucose metabolism, intestinal microbiome composition, and intestinal health indices, of [...] Read more.
Dysbiosis of intestinal ecology could be implicated in prediabetes. The aim of this pilot randomized controlled trial (RCT) was to collect preliminary data on the effects of probiotic supplementation (Vivomixx©) on markers of glucose metabolism, intestinal microbiome composition, and intestinal health indices, of prediabetic adolescents. The intervention group was administered probiotic sachets twice daily for 4 months, while both intervention and control groups received weekly consultation sessions for a healthier lifestyle. Thirty-two participants were recruited (1.3 participants per month) and were randomized (16 in control and 16 in intervention group). Fifteen of them signed the inform consent and never entered the study (6 in control and 9 in intervention group). Thus, seventeen participants completed the study (10 in control and 7 in intervention group), with no serious adverse events. After the 4-month intervention, no difference was observed in the markers of glycemic control between the two groups, although a minor effect was observed for fasting glucose at 1-month, probably due to the initial higher adherence to the probiotic supplements. Modifications of the protocol procedures are warranted because of the high attrition rates and suboptimal compliance that were noted. Future studies and further RCTs with larger samples need to be conducted to fully elucidate the potential effects of probiotics in the glycemic control of prediabetic adolescents. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessArticle
Association of Serum PCSK9 Levels with Antibiotic Resistance and Severity of Disease in Patients with Bacterial Infections Admitted to Intensive Care Units
J. Clin. Med. 2019, 8(10), 1742; https://doi.org/10.3390/jcm8101742 - 20 Oct 2019
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Abstract
Background: The results of several studies have suggested that infections and sepsis, either bacterial or viral, might be associated with elevated plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. Since there are no data on PCSK9 levels and antibiotic resistance or the severity [...] Read more.
Background: The results of several studies have suggested that infections and sepsis, either bacterial or viral, might be associated with elevated plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. Since there are no data on PCSK9 levels and antibiotic resistance or the severity of disease in patients with bacterial infections in intensive care units, the aim of this study was to investigate whether any such associations exist. Methods: 100 patients (46 males, mean age 67.12 ± 1.34 years) with bacterial infections who were staying in an intensive care unit (ICU) longer than 48 h but less than 7 days and who were not receiving corticosteroids were analyzed. Their serum levels of albumin, C-reactive protein, glucose, lactate, blood urea nitrogen, prothrombin (international normalized ratio), total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, PCSK9, and procalcitonin were measured. The severity of the patients’ condition was assessed by using the Glasgow Coma Scale (GCS), the Sequential Organ Failure Assessment (SOFA), and the Acute Physiology and Chronic Health Evaluation II (APACHE II) scales. Results: Using a hierarchical regression modeling approach, no significant association was found between PCSK9 levels and either the severity of disease (APACHE II, SOFA, and GCS) indices or resistance to antibiotics. Conclusion: The results suggest that there is no association between PCSK9 levels and resistance to antibiotics or the condition of patients hospitalized in intensive care units. Full article
(This article belongs to the Section Pharmacology)
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Open AccessReview
Hypothalamic Endocrine Tumors: An Update
J. Clin. Med. 2019, 8(10), 1741; https://doi.org/10.3390/jcm8101741 - 20 Oct 2019
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Abstract
The hypothalamus is the site of synthesis and secretion of a number of endocrine peptides that are involved in the regulation of hormonal activity of the pituitary and other endocrine targets. Tumors of the hypothalamus have been recognized to have both structural and [...] Read more.
The hypothalamus is the site of synthesis and secretion of a number of endocrine peptides that are involved in the regulation of hormonal activity of the pituitary and other endocrine targets. Tumors of the hypothalamus have been recognized to have both structural and functional effects including hormone hypersecretion. The classification of these tumors has advanced over the last few years, and biomarkers are now available to classify these tumors and provide accurate structure–function correlations. This review provides an overview of tumors in this region that is critical to metabolic homeostasis with a focus on advances in the diagnosis of gangliocytomas, neurocytomas, and pituicytomas that are unique to this region. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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Open AccessArticle
Antibiotic Use and Long-Term Outcome in Patients with Tick-Borne Encephalitis and Co-Infection with Borrelia Burgdorferi Sensu Lato in Central Europe. A Retrospective Cohort Study
J. Clin. Med. 2019, 8(10), 1740; https://doi.org/10.3390/jcm8101740 - 20 Oct 2019
Viewed by 171
Abstract
In this retrospective cohort study of patients with tick-borne encephalitis (TBE), the clinical outcome in relation to co-infection with B. burgdorferi sensu lato (s.l.) and, specifically, the effect of antibiotic treatment on clinical outcome in patients with TBE who were seropositive for borreliae [...] Read more.
In this retrospective cohort study of patients with tick-borne encephalitis (TBE), the clinical outcome in relation to co-infection with B. burgdorferi sensu lato (s.l.) and, specifically, the effect of antibiotic treatment on clinical outcome in patients with TBE who were seropositive for borreliae but who did not fulfil clinical or microbiologic criteria for proven co-infection, were assessed at a single university medical center in Slovenia, a country where TBE and Lyme borreliosis are endemic with high incidence. Among 684 patients enrolled during a seven-year period from 2007 through 2013, 382 (55.8%) had TBE alone, 62 (9.1%) had proven co-infection with borreliae and 240 (35.1%) had possible co-infection. The severity of acute illness was similar in all the groups. The odds for incomplete recovery decreased during a 12-month follow-up but were higher in women, older patients, and in those with more severe acute illness. Incomplete recovery was not associated with either proven (odds ratio (OR) 1.21, 95% confidence interval (CI) 0.49–2.95; p = 0.670) or possible co-infection (OR 0.95, 95% CI 0.55–1.65; p = 0.853). Among patients with possible co-infection, older patients were more likely to be prescribed antibiotics, but the odds for incomplete recovery were similar in those who received antibiotics and those who did not (OR 0.82, 95% CI 0.36–1.87; p = 0.630), suggesting that routine antibiotic treatment in patients with TBE and possible co-infection may not be warranted. Full article
(This article belongs to the Section Microbiology & Parasitology)
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Open AccessArticle
Transient Laterality of Cerebral Oxygenation Changes in Response to Head-of-Bed Manipulation in Acute Ischemic Stroke
J. Clin. Med. 2019, 8(10), 1739; https://doi.org/10.3390/jcm8101739 - 19 Oct 2019
Viewed by 178
Abstract
Background: Cerebral oxygenation monitoring provides important information for optimizing individualized management in patients with acute ischemic stroke (AIS). Although changes in cerebral oxygenation are known to occur in response to head-of-bed (HOB) elevation within 72 h after onset, changes in cerebral oxygenation during [...] Read more.
Background: Cerebral oxygenation monitoring provides important information for optimizing individualized management in patients with acute ischemic stroke (AIS). Although changes in cerebral oxygenation are known to occur in response to head-of-bed (HOB) elevation within 72 h after onset, changes in cerebral oxygenation during stroke recovery are unclear. We compared changes in total- (tHb), oxygenated- (HbO2), and deoxygenated-hemoglobin (deoxyHb) concentrations in response to HOB manipulation between the timeframes within 72 h and 7–10 days after AIS onset. Methods: We measured forehead ΔtHb, ΔHbO2, and ΔdeoxyHb in response to HOB elevation (30°) within 72 h (first measurement) and 7–10 days (second measurement) after AIS onset using time-resolved near-infrared spectroscopy. Results: We enrolled 30 participants (mean age 72.8 ± 11.3 years; 13 women) with a first AIS. There were no significant differences in ΔtHb, ΔHbO2, or ΔdeoxyHb measurements on the infarct or contra-infarct side. At the first measurement, ΔtHb, ΔHbO2, and ΔdeoxyHb measured on the contra-infarct side did not correlate with those measured on the infarct side: ΔtHb (r = 0.114, p = 0.539); ΔHbO2 (r = 0.143, p = 0.440); ΔdeoxyHb (r = 0.227, p = 0.221). Notably, at the second measurement, correlation coefficients of ΔtHb and ΔHbO2 between the contra-infarct and infarct sides were statistically significant: ΔtHb (r = 0.491, p = 0.008); ΔHbO2 (r = 0.479, p = 0.010); ΔdeoxyHb (r = 0.358, p = 0.054). Conclusion: Although changes in cerebral oxygenation in response to HOB elevation had a laterality difference between hemispheres within 72 h of AIS onset, the difference had decreased, at least partially, 7–10 days after AIS onset. Full article
Open AccessArticle
Effects of Osteopathic Visceral Treatment in Patients with Gastroesophageal Reflux: A Randomized Controlled Trial
J. Clin. Med. 2019, 8(10), 1738; https://doi.org/10.3390/jcm8101738 - 19 Oct 2019
Viewed by 197
Abstract
Osteopathic manual treatment has been recommended as a non-pharmacological therapy for Gastroesophageal Reflux Disease (GERD). However, to date, no study has supported the effectiveness of this intervention with respect to the symptoms of the disease. Our goal was to assess the effect of [...] Read more.
Osteopathic manual treatment has been recommended as a non-pharmacological therapy for Gastroesophageal Reflux Disease (GERD). However, to date, no study has supported the effectiveness of this intervention with respect to the symptoms of the disease. Our goal was to assess the effect of an osteopathic manual technique for the lower esophageal sphincter on GERD symptoms, cervical mobility and on the C4 spinous process pressure pain threshold (PPTs). Methods: A randomized, double-blind placebo-controlled trial was performed. Sixty subjects suffering from GERD participated in this study and were randomly assigned to either an experimental group (EG) (n = 29), who received the osteopathic technique for the lower esophageal sphincter, or to a control group (CG) (n = 31), who received a manual contact, which mimicked the osteopathic technique without exerting any therapeutic force. Randomization was computer-generated, with allocation concealed by sequentially numbered, opaque, sealed envelopes. The GerdQ questionnaire was used to assess symptom changes the week after intervention. Cervical Range of Motion (CROM) and algometer were used to evaluate cervical mobility and PPTs before and after both treatments. Before–after between groups comparison (t-test) was used for statistical analysis of the outcome, with two measurement points (GerdQ), while repeated-measures ANOVA was used for those outcomes with four measurement points (CROM and PPT). Results: The application of the osteopathic manual treatment in subjects with GERD produced a significant improvement in symptoms one week after the intervention (p = 0.005) with a between-groups difference of 1.49 points in GerdQ score (95% CI: 0.47–2.49). PPT C4 improved in the EG after the treatment (p = 0.034; η2 = 0.048) (between-groups difference 8.78 Newton/cm2; 95% CI: 0.48–17.09). CROM also increased in the EG compared to the CG (p < 0.001; η2 = 0.108) (between-groups difference 33.89 degrees; 95% CI: 15.17–52.61). Conclusions: The manual osteopathic technique produces an improvement in GERD symptoms one week after treatment, cervical mobility, and PPTs. This may mean that osteopathic treatment is useful for improving symptoms of GERD. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessReview
Advances in Understanding the Relationship between Sleep and Attention Deficit-Hyperactivity Disorder (ADHD)
J. Clin. Med. 2019, 8(10), 1737; https://doi.org/10.3390/jcm8101737 - 19 Oct 2019
Viewed by 239
Abstract
Starting from the consolidated relationship between sleep and cognition, we reviewed the available literature on the association between Attention Deficit-Hyperactivity Disorder (ADHD) and sleep. This review analyzes the macrostructural and microstructural sleep features, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [...] Read more.
Starting from the consolidated relationship between sleep and cognition, we reviewed the available literature on the association between Attention Deficit-Hyperactivity Disorder (ADHD) and sleep. This review analyzes the macrostructural and microstructural sleep features, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria (PRISMA). We included the polysomnographic studies published in the last 15 years. The results of macrostructural parameters are mixed. Almost half of the 18 selected investigations did not find differences between sleep architecture of children with ADHD and controls. Five studies observed that children with ADHD show a longer Rapid Eye Movement (REM) sleep duration than controls. Eight studies included microstructural measures. Remarkable alterations in sleep microstructure of ADHD are related to slow wave activity (SWA) and theta oscillations, respectively, during Non-REM (NREM) and REM sleep. Specifically, some studies found higher SWA in the ADHD group than controls. Similarly, higher theta activity appears to be detrimental for memory performance and inhibitory control in ADHD. These patterns could be interpreted as a maturational delay in ADHD. Also, the increased amount of these activities would be consistent with the hypothesis that the poor sleep could imply a chronic sleep deprivation in children with ADHD, which in turn could affect their cognitive functioning. Full article
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Open AccessArticle
Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?
J. Clin. Med. 2019, 8(10), 1736; https://doi.org/10.3390/jcm8101736 - 19 Oct 2019
Viewed by 107
Abstract
Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had [...] Read more.
Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. Methods: between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ≥15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan–Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. Results: a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. Conclusion: N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessArticle
Associations between Prenatal Physical Activity and Neonatal and Obstetric Outcomes—A Secondary Analysis of the Cluster-Randomized GeliS Trial
J. Clin. Med. 2019, 8(10), 1735; https://doi.org/10.3390/jcm8101735 - 19 Oct 2019
Viewed by 99
Abstract
Prenatal physical activity (PA) was discussed to decrease the incidence of obstetric and neonatal complications. In this secondary cohort analysis of the cluster-randomized GeliS (“healthy living in pregnancy”) trial, associations between prenatal PA and such outcomes were investigated. PA behavior was assessed twice, [...] Read more.
Prenatal physical activity (PA) was discussed to decrease the incidence of obstetric and neonatal complications. In this secondary cohort analysis of the cluster-randomized GeliS (“healthy living in pregnancy”) trial, associations between prenatal PA and such outcomes were investigated. PA behavior was assessed twice, before or during the 12th week (baseline, T0) and after the 29th week of gestation (T1), using the self-reported Pregnancy Physical Activity Questionnaire. Obstetric and neonatal data were collected in the routine care setting. Data were available for 87.2% (n = 1994/2286) of participants. Significant differences between the offspring of women who adhered to PA recommendations at T1 and offspring of inactive women were found in birth weight (p = 0.030) but not in other anthropometric parameters. Sedentary behavior was inversely associated with birth weight at T1 (p = 0.026) and, at both time points, with an increase in the odds of low birth weight (T0: p = 0.004, T1: p = 0.005). Light-intensity PA at T0 marginally increased the odds of caesarean section (p = 0.032), but neither moderate-intensity nor vigorous-intensity activity modified the risk for caesarean delivery at any time point. The present analyses demonstrated associations between prenatal PA and some neonatal and obstetric outcomes. Full article
(This article belongs to the Special Issue Health in Preconception Pregnancy and Postpartum)
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Open AccessArticle
Medication-Taking Habit and Outcome of Glucosamine Sulfate for Osteoarthritis Patients Influenced by National Health Insurance Regulations in Taiwan
J. Clin. Med. 2019, 8(10), 1734; https://doi.org/10.3390/jcm8101734 - 19 Oct 2019
Viewed by 97
Abstract
This study compared the dosage and different medication-taking habits of glucosamine sulfate (GS) for osteoarthritis patients and evaluated the influence of the National Health Insurance (NHI) prescription guidelines. The subjects were collected from the Taiwan NHI Research Database from 1 January 2004, to [...] Read more.
This study compared the dosage and different medication-taking habits of glucosamine sulfate (GS) for osteoarthritis patients and evaluated the influence of the National Health Insurance (NHI) prescription guidelines. The subjects were collected from the Taiwan NHI Research Database from 1 January 2004, to 31 December 2008, and 10,501 osteoarthritis patients were included. Then, 271 patients who continuously used nonsteroidal anti-inflammatory drug (NSAIDs) and started to receive glucosamine for the first time since 2005 (no glucosamine use in 2004) were compared with 593 age-matched patients who continuously used NSAIDs but never received any glucosamine drugs from 2004 to 2008. The mean treatment duration of the glucosamine-treated and NSAID-treated groups was 40.38 ± 7.89 and 45.82 ± 3.89 months, respectively. The most common medication-taking habit was 250 mg 3 times a day for 3 months and discontinued for 3 months. It was as indicated and covered by the NHI. Only 0.7% of patients used the recommended daily dosage of 1500 mg. Patients using GS surprisingly had a higher incidence rate of joint replacement surgery than those who did not use GS. The NHI prescription guidelines may cause patient selection bias, which decreases the efficacy of GS. Moreover, patients tend to have an altered medication-taking habit, with a daily dosage of 750 mg, which is lower than the recommended therapeutic dose. Full article
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Open AccessReview
Intraocular Biopsy and ImmunoMolecular Pathology for “Unmasking” Intraocular Inflammatory Diseases
J. Clin. Med. 2019, 8(10), 1733; https://doi.org/10.3390/jcm8101733 - 19 Oct 2019
Viewed by 111
Abstract
Intraocular inflammation can hide a variety of eye pathologies. In 33% of cases, to obtain a correct diagnosis, investigation of the intraocular sample is necessary. The combined analyses of the intraocular biopsy, using immuno-pathology and molecular biology, point to resolve the diagnostic dilemmas [...] Read more.
Intraocular inflammation can hide a variety of eye pathologies. In 33% of cases, to obtain a correct diagnosis, investigation of the intraocular sample is necessary. The combined analyses of the intraocular biopsy, using immuno-pathology and molecular biology, point to resolve the diagnostic dilemmas in those cases where history, clinical tests, and ophthalmic and systemic examinations are inconclusive. In such situations, the teamwork between the ophthalmologist and the molecular pathologist is critically important to discriminate between autoimmune diseases, infections, and intraocular tumors, including lymphoma and metastases, especially in those clinical settings known as masquerade syndromes. This comprehensive review focuses on the diagnostic use of intraocular biopsy and highlights its potential to enhance research in the field. It describes the different surgical techniques of obtaining the biopsy, risks, and complication rates. The review is organized according to the anatomical site of the sample: I. anterior chamber containing aqueous humor, II. iris and ciliary body, III. vitreous, and IV. choroid and retina. We have excluded the literature concerning biopsy for choroidal melanoma and retinoblastoma, as this is a specialized area more relevant to ocular oncology. Full article
(This article belongs to the Special Issue Application of Retinal and Optic Nerve Imaging in Clinical Medicine)
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Open AccessArticle
Pre-, Intra-, and Post-Operative Evaluation of Extraocular Muscle Insertions Using Optical Coherence Tomography: A Comparison of Four Devices
J. Clin. Med. 2019, 8(10), 1732; https://doi.org/10.3390/jcm8101732 - 19 Oct 2019
Viewed by 108
Abstract
OCT (optical coherence tomography) is widely used in ophthalmology and pediatric ophthalmology, but limited research has been done on the use of OCT in strabismus. This study investigates the use of different OCT machines to image rectus muscle insertions pre-, intra-, and post-operatively [...] Read more.
OCT (optical coherence tomography) is widely used in ophthalmology and pediatric ophthalmology, but limited research has been done on the use of OCT in strabismus. This study investigates the use of different OCT machines to image rectus muscle insertions pre-, intra-, and post-operatively in pediatric strabismus patients. The OCT machines used in the study were a Bioptigen (Leica Microsystems Inc., Buffalo Grove, IL, USA), Spectralis HRA+OCT with Anterior Segment Module (Heidelberg Engineering, Heidelberg, Germany), Visante (Carl Zeiss, Oberkochen, Germany), and Zeiss Rescan 700 (Carl Zeiss, Oberkochen, Germany). Measurements from the machines were compared with the caliper distance measured during the strabismus surgery before disinsertion or after reattachment. The OCT machines had moderate (Bioptigen: 0.62) to good intraclass correlation coefficients (Rescan: 0.83, Spectralis: 0.85, Visante: 0.88) with intra-operative measurements. To our knowledge, this is the first study to use an operating microscope with integrated intra-operative OCT to image rectus muscle insertions. OCT is a useful tool in strabismus surgical patients in the pre-, intra-, and post-operative settings, particularly in patients who have had previous surgery, when the muscle insertion is unknown. The ability to accurately image rectus muscle insertions has significant implications for the management of strabismus patients. Full article
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Open AccessArticle
Acute Kidney Injury and Septic Shock—Defined by Updated Sepsis-3 Criteria in Critically Ill Patients
J. Clin. Med. 2019, 8(10), 1731; https://doi.org/10.3390/jcm8101731 - 18 Oct 2019
Viewed by 188
Abstract
Sepsis is commonly associated with acute kidney injury (AKI), particularly in those requiring dialysis (AKI-D). To date, Sepsis-3 criteria have not been applied to AKI-D patients. We investigated sepsis prevalence defined by Sepsis-3 criteria and evaluated the outcomes of septic-associated AKI-D among critically [...] Read more.
Sepsis is commonly associated with acute kidney injury (AKI), particularly in those requiring dialysis (AKI-D). To date, Sepsis-3 criteria have not been applied to AKI-D patients. We investigated sepsis prevalence defined by Sepsis-3 criteria and evaluated the outcomes of septic-associated AKI-D among critically ill patients. Using the data collected from a prospective multi-center observational study, we applied the Sepsis-3 criteria to critically ill AKI-D patients treated in intensive care units (ICUs) in 30 hospitals between September 2014 and December 2015. We described the prevalence, outcomes, and characteristics of sepsis as defined by the screening Sepsis-3 criteria among AKI-D patients, and compared the outcomes of AKI-D patients with or without sepsis using the Sepsis-3 criteria. A total of 1078 patients (median 70 years; 673 (62.4%) men) with AKI-D were analyzed. The main etiology of AKI was sepsis (71.43%) and the most frequent indication for acute dialysis was oliguria (64.4%). A total of 577 (53.3% of 1078 patients) met the Sepsis-3 criteria, and 206 among the 577 patients (19.1%) had septic shock. Having sepsis and septic shock were independently associated with 90-day mortality among these ICU AKI-D patients (hazard ratio (HR) 1.23 (p = 0.027) and 1.39 (p = 0.004), respectively). Taking mortality as a competing risk factor, AKI-D patients with septic shock had a significantly reduced chance of weaning from dialysis at 90 days than those without sepsis (HR 0.65, p = 0.026). The combination of the Sepsis-3 criteria with the AKI risk score led to better performance in forecasting 90-day mortality. Sepsis affects more than 50% of ICU AKI patients requiring dialysis, and one-fifth of these patients had septic shock. In AKI-D patients, coexistent with or induced by sepsis (as screened by the Sepsis-3 criteria), there is a significantly higher mortality and reduced chance of recovering sufficient renal function, when compared to those without sepsis. Full article
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Open AccessArticle
Laxer Clinical Criteria for Gaming Disorder May Hinder Future Efforts to Devise an Efficient Diagnostic Approach: A Tree-Based Model Study
J. Clin. Med. 2019, 8(10), 1730; https://doi.org/10.3390/jcm8101730 - 18 Oct 2019
Viewed by 191
Abstract
Internet Gaming Disorder (IGD) has been recognized in May 2013 and can be evaluated using the criteria developed by American Psychiatric Association (APA). The present study investigated the role each IGD criteria plays in diagnosing disordered gaming. A total of 3,377 participants (mean [...] Read more.
Internet Gaming Disorder (IGD) has been recognized in May 2013 and can be evaluated using the criteria developed by American Psychiatric Association (APA). The present study investigated the role each IGD criteria plays in diagnosing disordered gaming. A total of 3,377 participants (mean age 20 years, SD = 4.3 years) participated in the study. The data collected was scrutinized to detect patterns of IGD using Conditional Inference Tree (Ctree), a sophisticated machine algorithm. Participants provided basic sociodemographic information and completed the Internet Gaming Disorder Scale–Short-Form (IGDS9-SF). The results identified classes of IGD-related symptoms, indicating that endorsing ‘withdrawal’ and ‘loss of control’ increases the probability of disordered gaming by 77.77% while endorsement of ‘withdrawal’, ‘loss of control’ and ‘negative consequences’ increases the probability of disordered gaming by 26.66%. Moreover, lack of endorsement of ‘withdrawal’ and endorsement of ‘preoccupation’ increases the likelihood of disordered gaming by 7.14%. Taken together, the results obtained illustrate that different IGD criteria can present with different clinical weighing as unique diagnostic roles in the development of disordered gaming can be evidenced by each criterion. Moreover, the present findings help inform future revisions of diagnostic manuals and helps enhancing the assessment of IGD in the future. Additional research and clinical implications are discussed. Full article
Open AccessArticle
Positive Impact of Expert Reference Center Validation on Performance of Next-Generation Sequencing for Genetic Diagnosis of Autoinflammatory Diseases
J. Clin. Med. 2019, 8(10), 1729; https://doi.org/10.3390/jcm8101729 - 18 Oct 2019
Viewed by 192
Abstract
Monogenic autoinflammatory diseases (AIDs) are caused by variants in genes that regulate innate immunity. The current diagnostic performance of targeted next-generation sequencing (NGS) for AIDs is low. We assessed whether pre-analytic advice from expert clinicians could help improve NGS performance from our 4 [...] Read more.
Monogenic autoinflammatory diseases (AIDs) are caused by variants in genes that regulate innate immunity. The current diagnostic performance of targeted next-generation sequencing (NGS) for AIDs is low. We assessed whether pre-analytic advice from expert clinicians could help improve NGS performance from our 4 years of experience with the sequencing of a panel of 55 AIDs genes. The study included all patients who underwent routine NGS testing between September 2014 and January 2019 at the laboratory of autoinflammatory diseases (Montpellier, France). Before March 2018, all medical requests for testing were accepted. After this time, we required validation by a reference center before NGS: the positive advice could be obtained after a face-to-face consultation with the patient or presentation of the patient’s case at a multidisciplinary staff meeting. Targeted NGS resulted in an overall 7% genetic confirmation, which is consistent with recent reports. The diagnostic performance before and after implementation of the new pre-requisite increased from 6% to 10% (p = 0.021). Our study demonstrated, for the first time, the beneficial effect of a two-step strategy (clinical expert advice, then genetic testing) for AIDs diagnosis and stressed the possible usefulness of the strategy in anticipation of the development of pan-genomic analyses in routine settings. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessArticle
Evaluation of a Non-Parenteral Opioid Analgesia Protocol for Acute Sickle Cell Pain Episodes in Children
J. Clin. Med. 2019, 8(10), 1728; https://doi.org/10.3390/jcm8101728 - 18 Oct 2019
Viewed by 112
Abstract
We evaluated a protocol comprising intranasal diamorphine (IND) combined with oral short and modified-release morphine for children at the emergency department (ED) with acute painful episodes of sickle cell disease (SCD). In a retrospective audit of 83 episodes in 38 children, the mean [...] Read more.
We evaluated a protocol comprising intranasal diamorphine (IND) combined with oral short and modified-release morphine for children at the emergency department (ED) with acute painful episodes of sickle cell disease (SCD). In a retrospective audit of 83 episodes in 38 children, the mean time between arrival in the treatment area and the administration of IND was 10 min (range <5 min to 1.39 h). IND was administered in <5 min in 43 (51.6%), and in <20 min in 75 (90.4%) episodes. Persisting pain, requiring background analgesia with modified-release oral morphine, was required in 25 (30.1%) episodes. Inadequate control of pain requiring a switch to intravenous morphine PCA was required in eight episodes in four patients. Acute chest syndrome (ACS) developed in four of 83 episodes (4.8%, 95% CI 0.2–9.4%) and in four of 38 children (10.5%, 95% CI 0.7–20.5%). In conclusion, this protocol enabled the rapid administration of strong opioid analgesia in an ED setting, and may reduce the short and long-term adverse effects associated with parenteral opioids in children. There was no evidence of an increased incidence of ACS associated with use of oral morphine. Full article
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