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J. Clin. Med., Volume 8, Issue 1 (January 2019)

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Open AccessArticle Glutathione Metabolism, Mitochondria Activity, and Nitrosative Stress in Patients Treated for Mandible Fractures
J. Clin. Med. 2019, 8(1), 127; https://doi.org/10.3390/jcm8010127
Received: 29 December 2018 / Revised: 19 January 2019 / Accepted: 20 January 2019 / Published: 21 January 2019
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Abstract
The aim of the study was to evaluate the effect of titanium bone fixations on mitochondrial activity, reactive oxygen species (ROS) production, glutathione metabolism, and selected markers of oxidative/nitrosative stress in the periosteum-like tissue of patients treated with mandible fractures. The study group [...] Read more.
The aim of the study was to evaluate the effect of titanium bone fixations on mitochondrial activity, reactive oxygen species (ROS) production, glutathione metabolism, and selected markers of oxidative/nitrosative stress in the periosteum-like tissue of patients treated with mandible fractures. The study group consisted of 30 patients with bilateral fractures of the mandible body eligible for surgical treatment. Our study is the first one that indicates disturbances of mitochondrial activity as well as a higher production of ROS in the periosteum-like tissue covering titanium fixations of the mandible. We also found significantly higher levels of reduced glutathione and enhanced activity of glutathione reductase in the periosteum homogenates of patients in the study group compared to the control group. Levels of nitrosative (S-nitrosothiols, peroxynitrite, nitrotyrosine) and oxidative stress biomarkers (malondialdehyde, protein carbonyls, dityrosine, kynurenine, and N-formylkynurenine) were statistically elevated in periosteum-like tissue covering titanium fixations. Although exposure to titanium fixations induces local antioxidant mechanisms, patients suffer oxidative damage, and in the periosteum-like tissue the phenomenon of metallosis was observed. Titanium implants cause oxidative/nitrosative stress as well as disturbances in mitochondrial activity. Full article
(This article belongs to the Section Orthopedics)
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Open AccessArticle Evidence for a Common Genetic Origin of Classic and Milder Adult-Onset Forms of Isolated Hypogonadotropic Hypogonadism
J. Clin. Med. 2019, 8(1), 126; https://doi.org/10.3390/jcm8010126
Received: 21 November 2018 / Revised: 16 January 2019 / Accepted: 17 January 2019 / Published: 21 January 2019
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Abstract
Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism (IHH) in males, whereas classic IHH is a rare congenital condition with a strong genetic background. Since we recently uncovered a frequent familiarity for classic IHH among patients [...] Read more.
Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism (IHH) in males, whereas classic IHH is a rare congenital condition with a strong genetic background. Since we recently uncovered a frequent familiarity for classic IHH among patients with mild adult-onset hypogonadism (AO-IHH), here we performed a genetic characterization by next generation sequencing of 160 males with classic or “functional” forms. The prevalence of rare variants in 28 candidate genes was significantly higher than in controls in all IHH patients, independently of the age of IHH onset, degree of hypogonadism or presence of obesity. In fact, it did not differ among patients with classic or milder forms of IHH, however particular genes appear to be more specifically associated with one or the other category of IHH. ROC curves showed that Total Testosterone <6.05 nmol/L and an age of onset <41 years are sensitive cutoffs to identify patients with significantly higher chances of harboring rare IHH gene variants. In conclusion, rare IHH genes variants can frequently predispose to AO-IHH with acquired mild hormonal deficiencies. The identification of a genetic predisposition can improve the familial and individual management of AO-IHH and explain the heritability of congenital IHH. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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Open AccessArticle Total Reference Air Kerma is Associated with Late Bowel Morbidity in Locally Advanced Cervical Cancer Patients Treated with Image-Guided Adaptive Brachytherapy
J. Clin. Med. 2019, 8(1), 125; https://doi.org/10.3390/jcm8010125
Received: 22 December 2018 / Revised: 12 January 2019 / Accepted: 16 January 2019 / Published: 21 January 2019
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Abstract
No dose volume parameter has been identified to predict late bowel toxicities in locally advanced cervical cancer (LACC) patients treated with image-guided adaptive brachytherapy. We examined the incidence of bowel toxicities according to the total reference air kerma (TRAK) in 260 LACC patients. [...] Read more.
No dose volume parameter has been identified to predict late bowel toxicities in locally advanced cervical cancer (LACC) patients treated with image-guided adaptive brachytherapy. We examined the incidence of bowel toxicities according to the total reference air kerma (TRAK) in 260 LACC patients. In both univariate and multivariate analysis, late morbidity positively correlated with a TRAK ≥2 cGy (centigray) at 1 meter, emphasizing the importance of this parameter in term of late bowel morbidity. Objective: There is no validated dose volume parameter to predict late bowel toxicities in cervical cancer patients treated with image-guided adaptive brachytherapy (IGABT). We examined the incidence of bowel toxicities according to the TRAK, which is proportional to the integral dose to the patients. Material/Methods: Clinical data of 260 LACC patients treated with curative intent from 2004 to 2016 were examined. Patients received chemoradiation plus a pulse-dose rate IGABT boost. The relationship between TRAK and morbidity was assessed by Kaplan-Meier method, log-rank tests, and Cox proportional-hazards model on event-free periods. Results: Median follow-up was 5.2 years (SE (Standard Error): 0.21). Probability of survival without late bowel toxicity Grade ≥ 2 rate for patients without recurrence (n = 227) at 5 years was 66.4% (SE 3.7). In univariate analysis, bowel and/or sigmoid dose/volume parameters were not significant. Late morbidity positively correlated with active smoking, CTVHR volume >25 cm3, and a TRAK ≥2 cGy at 1 meter. In multivariate analysis, the following factors were significant: Active smoking (p < 0.001; HR: 2.6; 95%CI: 1.4–5.0), and the TRAK (p = 0.02; HR: 2.4; 95%CI: 1.2–5.0). Conclusion: TRAK was associated with late bowel toxicities probability, suggesting that the integral dose should be considered, even in the era of IGABT. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle Application of a Perception Neuron® System in Simulation-Based Surgical Training
J. Clin. Med. 2019, 8(1), 124; https://doi.org/10.3390/jcm8010124
Received: 18 December 2018 / Revised: 6 January 2019 / Accepted: 17 January 2019 / Published: 21 January 2019
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Abstract
While multiple studies show that simulation methods help in educating surgical trainees, few studies have focused on developing systems that help trainees to adopt the most effective body motions. This is the first study to use a Perception Neuron® system to evaluate [...] Read more.
While multiple studies show that simulation methods help in educating surgical trainees, few studies have focused on developing systems that help trainees to adopt the most effective body motions. This is the first study to use a Perception Neuron® system to evaluate the relationship between body motions and simulation scores. Ten medical students participated in this study. All completed two standard tasks with da Vinci Skills Simulator (dVSS) and five standard tasks with thyroidectomy training model. This was repeated. Thyroidectomy training was conducted while participants wore a perception neuron. Motion capture (MC) score that indicated how long the tasks took to complete and each participant’s economy-of-motion that was used was calculated. Correlations between the three scores were assessed by Pearson’s correlation analyses. The 20 trials were categorized as low, moderate, and high overall-proficiency by summing the training model, dVSS, and MC scores. The difference between the low and high overall-proficiency trials in terms of economy-of-motion of the left or right hand was assessed by two-tailed t-test. Relative to cycle 1, the training model, dVSS, and MC scores all increased significantly in cycle 2. Three scores correlated significantly with each other. Six, eight, and six trials were classified as low, moderate, and high overall-proficiency, respectively. Low- and high-scoring trials differed significantly in terms of right (dominant) hand economy-of-motion (675.2 mm and 369.4 mm, respectively) (p = 0.043). Perception Neuron® system can be applied to simulation-based training of surgical trainees. The motion analysis score is related to the traditional scoring system. Full article
(This article belongs to the Special Issue Robotic Surgery)
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Open AccessCase Report Dialysis or a Plant-Based Diet in Advanced CKD in Pregnancy? A Case Report and Critical Appraisal of the Literature
J. Clin. Med. 2019, 8(1), 123; https://doi.org/10.3390/jcm8010123
Received: 8 December 2018 / Revised: 7 January 2019 / Accepted: 8 January 2019 / Published: 20 January 2019
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Abstract
Pregnancy is increasingly reported in chronic kidney disease (CKD), reflecting higher awareness, improvements in materno-foetal care, and a more flexible attitude towards “allowing” pregnancy in the advanced stages of CKD. Success is not devoid of problems and an important grey area regards the [...] Read more.
Pregnancy is increasingly reported in chronic kidney disease (CKD), reflecting higher awareness, improvements in materno-foetal care, and a more flexible attitude towards “allowing” pregnancy in the advanced stages of CKD. Success is not devoid of problems and an important grey area regards the indications for starting dialysis (by urea level, clinical picture, and residual glomerular filtration rate) and for dietary management. The present case may highlight the role of plant-based diets in dietary management in pregnant CKD women, aimed at retarding dialysis needs. The case. A 28-year-old woman, affected by glomerulocystic disease and unilateral renal agenesis, in stage-4 CKD, was referred at the 6th week of amenorrhea: she weighed 40 kg (BMI 16.3), was normotensive, had no sign of oedema, her serum creatinine was 2.73 mg/dL, blood urea nitrogen (BUN) 35 mg/dL, and proteinuria 200 mg/24 h. She had been on a moderately protein-restricted diet (about 0.8 g/kg/real body weight, 0.6 per ideal body weight) since childhood. Low-dose acetylsalicylate was added, and a first attempt to switch to a protein-restricted supplemented plant-based diet was made and soon stopped, as she did not tolerate ketoacid and aminoacid supplementation. At 22 weeks of pregnancy, creatinine was increased (3.17 mg/dL, BUN 42 mg/dL), dietary management was re-discussed and a plant-based non-supplemented diet was started. The diet was associated with a rapid decrease in serum urea and creatinine; this favourable effect was maintained up to the 33rd gestational week when a new rise in urea and creatinine was observed, together with signs of cholestasis. After induction, at 33 weeks + 6 days, she delivered a healthy female baby, adequate for gestational age (39th centile). Urea levels decreased after delivery, but increased again when the mother resumed her usual mixed-protein diet. At the child’s most recent follow-up visit (age 4 months), development was normal, with normal weight and height (50th–75th centile). In summary, the present case confirms that a moderate protein-restricted diet can be prescribed in pregnancies in advanced CKD without negatively influencing foetal growth, supporting the importance of choosing a plant-based protein source, and suggests focusing on the diet’s effects on microcirculation to explain these favourable results. Full article
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Open AccessArticle The Conditions Under Which Piracetam Is Used and the Factors That Can Improve National Institute of Health Stroke Scale Score in Ischemic Stroke Patients and the Importance of Previously Unnoticed Factors From a Hospital-Based Observational Study in Taiwan
J. Clin. Med. 2019, 8(1), 122; https://doi.org/10.3390/jcm8010122
Received: 18 December 2018 / Revised: 15 January 2019 / Accepted: 17 January 2019 / Published: 20 January 2019
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Abstract
This study aimed to explore the associations of piracetam use and the clinical characteristics of NIHSS (National Institute of Health Stroke Scale) changes—the importance of which, as prognosis related factors, was previously unnoticed—and analyze the associations of piracetem with NIHSS changes by stratifying [...] Read more.
This study aimed to explore the associations of piracetam use and the clinical characteristics of NIHSS (National Institute of Health Stroke Scale) changes—the importance of which, as prognosis related factors, was previously unnoticed—and analyze the associations of piracetem with NIHSS changes by stratifying clinical characteristics. This observational retrospective study was conducted by enrolling patients based on 2483 stroke registration data cohorts from a 1200-bed regional Tungs’ Taichung MetroHarbor Hospital, located in central Taiwan from 1 January 1 2011 to 31 December 2015. Patients were excluded if they had intravenous a thrombolytic agent within 3 hours of symptoms onset (n = 49), incomplete or erroneous NIHSS scores (n = 953), or transient ischemia stroke (n = 130). Logistic regression model was applied for associating piracetam treatment and clinical characteristics with NIHSS score changes between admission and discharge, and subgroup analysis to assess the conditions under which piracetam can be used. Multivariate analysis revealed NIHSS scores improvement in atrial fibrillation, large-artery atherosclerosis, underweight, current smoker, ex-smoker, and piracetam. Subgroup analysis showed piracetam is beneficial in the following: age ≥75 years olds, males, those of normal weight, those who are obese, ex-smokers, those with hypertension, dyslipidemia, those without diabetes mellitus, nor atrial fibrillation. The selection of the conditions under which piracetam treatment should be given, and clinical characteristics, is important for NIHSS improvement of ischemic stroke patients in Taiwan. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessArticle Homocysteine: A Potential Biomarker for Diabetic Retinopathy
J. Clin. Med. 2019, 8(1), 121; https://doi.org/10.3390/jcm8010121
Received: 17 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 19 January 2019
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Abstract
Diabetic retinopathy (DR) is the most common cause of blindness in people under the age of 65. Unfortunately, the current screening process for DR restricts the population that can be evaluated and the disease goes undetected until irreversible damage occurs. Herein, we aimed [...] Read more.
Diabetic retinopathy (DR) is the most common cause of blindness in people under the age of 65. Unfortunately, the current screening process for DR restricts the population that can be evaluated and the disease goes undetected until irreversible damage occurs. Herein, we aimed to evaluate homocysteine (Hcy) as a biomarker for DR screening. Hcy levels were measured by enzyme-linked immuno sorbent assay (ELISA) and immunolocalization methods in the serum, vitreous and retina of diabetic patients as well as in serum and retina of different animal models of DM representing type 1 diabetes (streptozotocin (STZ) mice, Akita mice and STZ rats) and db/db mice which exhibit features of human type 2 diabetes. Our results revealed increased Hcy levels in the serum, vitreous and retina of diabetic patients and experimental animal models of diabetes. Moreover, optical coherence tomography (OCT) and fluorescein angiography (FA) were used to evaluate the retinal changes in mice eyes after Hcy-intravitreal injection into normal wild-type (WT) and diabetic (STZ) mice. Hcy induced changes in mice retina which were aggravated under diabetic conditions. In conclusion, our data reported Hcy as a strong candidate for use as a biomarker in DR screening. Targeting the clearance of Hcy could also be a future therapeutic target for DR. Full article
(This article belongs to the Section Ophthalmology)
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Open AccessReview The Diversity of Encephalitogenic CD4+ T Cells in Multiple Sclerosis and Its Animal Models
J. Clin. Med. 2019, 8(1), 120; https://doi.org/10.3390/jcm8010120
Received: 3 January 2019 / Revised: 15 January 2019 / Accepted: 15 January 2019 / Published: 19 January 2019
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Abstract
Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model [...] Read more.
Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model experiments, genome-wide association studies, and immune profiles of individuals with MS. Furthermore, disease modifying agents that target lymphocytes significantly reduce the rate of MS clinical exacerbations. However, the properties of myelin-reactive CD4+ T cells that are critical for their pathogenic activities are not understood completely. This article reviews the literature on encephalitogenic CD4+ T cells, with an emphasis on T-helper (Th) lineage and cytokine production. An increased understanding of the spectrum of encephalitogenic T cells and how they differ from protective subsets is necessary for the development of the next generation of more effective and safer immunomodulatory therapies customized for individuals with MS and related disorders. Full article
(This article belongs to the Special Issue Potential Pathogenic Mechanisms of Multiple Sclerosis)
Open AccessArticle Clinical and Rehabilitative Predictors of Peak Oxygen Uptake Following Cardiac Transplantation
J. Clin. Med. 2019, 8(1), 119; https://doi.org/10.3390/jcm8010119
Received: 21 December 2018 / Revised: 14 January 2019 / Accepted: 16 January 2019 / Published: 19 January 2019
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Abstract
The measurement of peak oxygen uptake (VO2peak) is an important metric for evaluating cardiac transplantation (HTx) eligibility. However, it is unclear which factors (e.g., recipient demographics, clinical parameters, cardiac rehabilitation (CR) participation) influence VO2peak following HTx. Consecutive HTx patients with [...] Read more.
The measurement of peak oxygen uptake (VO2peak) is an important metric for evaluating cardiac transplantation (HTx) eligibility. However, it is unclear which factors (e.g., recipient demographics, clinical parameters, cardiac rehabilitation (CR) participation) influence VO2peak following HTx. Consecutive HTx patients with cardiopulmonary exercise testing (CPET) between 2007–2016 were included. VO2peak was measured from CPET standard protocol. Regression analyses determined predictors of the highest post-HTx VO2peak (i.e., quartile 4: VO2peak > 20.1 mL/kg/min). One hundred-forty HTx patients (women: n = 41 (29%), age: 52 ± 12 years, body mass index (BMI): 27 ± 5 kg/m2) were included. History of diabetes (Odds Ratio (OR): 0.17, 95% Confidence Interval (CI): 0.04–0.77, p = 0.021), history of dyslipidemia (OR: 0.42, 95% CI: 0.19–0.93, p = 0.032), BMI (OR: 0.90, 95% CI: 0.82–0.99, p = 0.022), hemoglobin (OR: 1.29, 95% CI: 1.04–1.61, p = 0.020), white blood cell count (OR: 0.81, 95% CI: 0.66–0.98, p = 0.033), CR exercise sessions (OR: 1.10, 95% CI: 1.04–1.15, p < 0.001), and pre-HTx VO2peak (OR: 1.17, 95% CI: 1.07–1.29, p = 0.001) were significant predictors. Multivariate analysis showed CR exercise sessions (OR: 1.10, 95% CI: 1.03–1.16, p = 0.002), and pre-HTx VO2peak (OR: 1.16, 95% CI: 1.04–1.30, p = 0.007) were independently predictive of higher post-HTx VO2peak. Pre-HTx VO2peak and CR exercise sessions are predictive of a greater VO2peak following HTx. These data highlight the importance of CR exercise session attendance and pre-HTx fitness in predicting VO2peak post-HTx. Full article
(This article belongs to the Special Issue Cardiac Rehabilitation)
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Open AccessReview Effect of Statin Therapy on Arterial Wall Inflammation Based on 18F-FDG PET/CT: A Systematic Review and Meta-Analysis of Interventional Studies
J. Clin. Med. 2019, 8(1), 118; https://doi.org/10.3390/jcm8010118
Received: 3 November 2018 / Revised: 14 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
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Abstract
Aim. To evaluate by meta-analysis of interventional studies the effect of statin therapy on arterial wall inflammation. Background. Arterial exposure to low-density lipoprotein (LDL) cholesterol levels is responsible for initiation and progression of atherosclerosis and arterial wall inflammation. 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography [...] Read more.
Aim. To evaluate by meta-analysis of interventional studies the effect of statin therapy on arterial wall inflammation. Background. Arterial exposure to low-density lipoprotein (LDL) cholesterol levels is responsible for initiation and progression of atherosclerosis and arterial wall inflammation. 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (18F-FDG PET/CT) has been used to detect arterial wall inflammation and monitor the vascular anti-inflammatory effects of lipid-lowering therapy. Despite a number of statin-based interventional studies exploring 18F-FDG uptake, these trials have produced inconsistent results. Methods. Trials with at least one statin treatment arm were searched in PubMed-Medline, SCOPUS, ISI Web of Knowledge, and Google Scholar databases. Target-to-background ratio (TBR), an indicator of blood-corrected 18F-FDG uptake, was used as the target variable of the statin anti-inflammatory activity. Evaluation of studies biases, a random-effects model with generic inverse variance weighting, and sensitivity analysis were performed for qualitative and quantitative data assessment and synthesis. Subgroup and meta-regression analyses were also performed. Results. Meta-analysis of seven eligible studies, comprising 10 treatment arms with 287 subjects showed a significant reduction of TBR following statin treatment (Weighted Mean Difference (WMD): −0.104, p = 0.002), which was consistent both in high-intensity (WMD: −0.132, p = 0.019) and low-to-moderate intensity statin trials (WMD: −0.069, p = 0.037). Statin dose/duration, plasma cholesterol and C-reactive protein level changes, and baseline TBR did not affect the TBR treatment response to statins. Conclusions. Statins were effective in reducing arterial wall inflammation, as assessed by 18F-FDG PET/CT imaging. Larger clinical trials should clarify whether either cholesterol-lowering or other pleiotropic mechanisms were responsible for this effect. Full article
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Open AccessArticle The Future State of Newborn Stem Cell Banking
J. Clin. Med. 2019, 8(1), 117; https://doi.org/10.3390/jcm8010117
Received: 21 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
Newborn stem cell banking began with the establishment of cord blood banks more than 25 years ago. Over the course of nearly three decades, there has been considerable evolution in the clinical application of stem cells isolated from newborn tissues. The industry now [...] Read more.
Newborn stem cell banking began with the establishment of cord blood banks more than 25 years ago. Over the course of nearly three decades, there has been considerable evolution in the clinical application of stem cells isolated from newborn tissues. The industry now finds itself at an inflection point as personalized medicine and regenerative medicine continue to advance. In this review, we summarize our perspective on newborn stem cell banking in the context of the future potential that stem cells from perinatal tissues are likely to play in nascent applications. Specifically, we describe the relevance of newborn stem cell banking and how the cells stored can be utilized as starting material for the next generation of advanced cellular therapies and personalized medicine. Full article
(This article belongs to the Special Issue Biobanking and Regenerative Medicine)
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Open AccessArticle Inhibition of NADPH Oxidase 4 (NOX4) Signaling Attenuates Tuberculous Pleural Fibrosis
J. Clin. Med. 2019, 8(1), 116; https://doi.org/10.3390/jcm8010116
Received: 21 November 2018 / Revised: 15 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [NOX] enzymes serve several hemostatic and host defense functions in various lung diseases, but the role of NOX4 signaling in tuberculous pleurisy is not well understood. The role of NOX4 signaling in tuberculous pleural fibrosis was studied [...] Read more.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [NOX] enzymes serve several hemostatic and host defense functions in various lung diseases, but the role of NOX4 signaling in tuberculous pleurisy is not well understood. The role of NOX4 signaling in tuberculous pleural fibrosis was studied using invitro pleural mesothelial cell (PMC) experiments and a murine model of Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection. The production of NOX4 reactive oxygen species (NOX4–ROS) and the epithelial mesenchymal transition (EMT) in PMCs were both induced by heat-killed mycobacterium tuberculosis (HKMT). In cultured PMCs, HKMT-induced collagen-1 synthesis and EMT were blocked by pretreatment with small interfering RNA (siRNA) NOX4. Moreover, NOX4–ROS production and subsequent fibrosis were reduced by treatment with losartan and the toll-like receptor 4 (TLR4) inhibitor TAK-242. The HKMT-induced EMT and intracellular ROS production were mediated by NOX4 via the activation of extracellular signal-regulated kinase (ERK) signaling. Finally, in a BCG-induced pleurisy model, recruitment of inflammatory pleural cells, release of inflammatory cytokines, and thickened mesothelial fibrosis were attenuated by SiNOX4 compared to SiCon. Our study identified that HKMT-induced pleural fibrosis is mediated by NOX4–ERK–ROS via TLR4 and Angiotensin II receptor type1 (AT1R). There results suggest that NOX4 may be a novel therapeutic target for intervention in tuberculous pleural fibrosis. Full article
(This article belongs to the Special Issue The New Frontier in Pulmonary Fibrosis)
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Open AccessArticle Familial Aggregation of Psoriasis and Co-Aggregation of Autoimmune Diseases in Affected Families
J. Clin. Med. 2019, 8(1), 115; https://doi.org/10.3390/jcm8010115
Received: 1 January 2019 / Revised: 11 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
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Abstract
Psoriasis is considered to result from the interaction of genetic factors and environmental exposure. The evidence for familial aggregation in psoriasis has been reported but population-based studies related to the magnitude of genetic contribution to psoriasis are rare. This study aimed to evaluate [...] Read more.
Psoriasis is considered to result from the interaction of genetic factors and environmental exposure. The evidence for familial aggregation in psoriasis has been reported but population-based studies related to the magnitude of genetic contribution to psoriasis are rare. This study aimed to evaluate the relative risks of psoriasis in individuals with affected relatives and to calculate the proportion of genetic, shared, and non-shared environmental factors contributing to psoriasis. The study cohort included 69,828 patients diagnosed with psoriasis enrolled in National health Insurance in 2010. The adjusted relative risks (RR) for individuals with an affected first-degree relative and affected second-degree relative were 5.50 (95% CI (Confidence Interval), 5.19–5.82) and 2.54 (95% CI, 2.08–3.12) respectively. For those who have affected first-degree relatives, their RR was 1.45 (95% CI, 1.17–1.79) for Sjogren’s syndrome and 1.94 (95% CI, 1.15–3.27) for systemic sclerosis. This nationwide study ascertains that family history of psoriasis is a risk factor for psoriasis. Individuals with relatives affected by psoriasis have higher risks of developing some autoimmune diseases. Full article
(This article belongs to the Section Dermatology)
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Open AccessCase Report Acute IgA-Dominant Glomerulonephritis Associated with Syphilis Infection in a Pregnant Teenager: A New Disease Association
J. Clin. Med. 2019, 8(1), 114; https://doi.org/10.3390/jcm8010114
Received: 22 December 2018 / Revised: 8 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
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Abstract
Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in [...] Read more.
Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in a wider context, such as in the case reported in this paper, which for the first time describes an association between syphilis infection and IgA-dominant glomerulonephritis. A 16-year-old woman, referred to a general hospital due to a seizure, was found to be unknowingly pregnant. Based on hypertension and nephrotic proteinuria, she was initially diagnosed with PE. Immunological tests, as well as hepatitis and HIV tests showed negative results. However, secondary syphilis was diagnosed. In discordance with the PE diagnosis, urinalysis showed glomerular microhematuria with cellular casts. Proteinuria and hypertension did not remit after delivery, which was made via caesarean section, due to uncontrolled hypertension, at an estimated gestational age of 29 weeks. A male baby, weighing 1.1 kg (6.5 centile) was born. The baby was hospitalized in the neonatal intensive care unit, where he developed subependymal hemorrhage and thrombocytopenia, and neonatal syphilis was diagnosed. The mother underwent a kidney biopsy one week after delivery, leading to the diagnosis of IgA-dominant postinfectious glomerulonephritis. Mother and child were treated with support and antibiotic therapy, and were discharged in good clinical conditions four weeks later. Four months after delivery, the mother was normotensive without therapy, with normal kidney function and without hematuria or proteinuria. In conclusion, this case suggests that IgA-dominant postinfectious glomerulonephritis should be added to the spectrum of syphilis-associated glomerulonephritides, and underlines the need for a careful differential diagnosis with CKD in all cases of presumed PE. While diagnosis relies on kidney biopsy, urinary sediment, a simple and inexpensive test, can be the first step in distinguishing PE from other nephropathies. Full article
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Open AccessArticle Effect of Androgen-Deprivation Therapy on Bone Mineral Density in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(1), 113; https://doi.org/10.3390/jcm8010113
Received: 20 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
We aimed to evaluate the change in bone mineral density (BMD) in patients with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) compared to those with PCa or other urologic conditions not receiving ADT. Literature searches were conducted throughout October 2018. The eligibility [...] Read more.
We aimed to evaluate the change in bone mineral density (BMD) in patients with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) compared to those with PCa or other urologic conditions not receiving ADT. Literature searches were conducted throughout October 2018. The eligibility of each study was assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the Participant, Intervention, Comparator, Outcome, and Study design method. The outcomes analyzed were the mean difference (MD) of percent changes in BMD of lumbar spine, femur neck, and total hip. Five prospective cohort studies with a total of 533 patients were included in the present study. Statistically significant decreases of BMD change relative to the control group were observed in the ADT treatment group in the lumbar spine (MD −3.60, 95% CI −6.72 to −0.47, P = 0.02), femoral neck (MD −3.11, 95% CI −4.73 to −1.48, P = 0.0002), and total hip (MD −1.59, 95% CI −2.99 to −0.19, P = 0.03). There is a significant relationship between ADT and BMD reduction in patients with PCa. Regular BMD testing and the optimal treatment for BMD loss should, therefore, be considered in patients with PCa undergoing ADT. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle Molecular Profile of Advanced Non-Small Cell Lung Cancers in Octogenarians: The Door to Precision Medicine in Elderly Patients
J. Clin. Med. 2019, 8(1), 112; https://doi.org/10.3390/jcm8010112
Received: 13 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
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Abstract
Background: There is a pressing need to expand the evidence base in geriatric lung oncology. Most non-small cell lung cancers (NSCLCs) are diagnosed in the elderly, with approximately 15% of cases affecting octogenarians. Treatment-related decisions are challenging in this population, and the role [...] Read more.
Background: There is a pressing need to expand the evidence base in geriatric lung oncology. Most non-small cell lung cancers (NSCLCs) are diagnosed in the elderly, with approximately 15% of cases affecting octogenarians. Treatment-related decisions are challenging in this population, and the role of biologically driven therapies is still underrated. Methods: A single-institution cohort of 76 NSCLCs from octogenarian patients was submitted to molecular analysis using a next-generation sequencing (NGS) multigene panel, fluorescence in situ hybridization (FISH) analyses, and immunohistochemistry for PD-L1 assessment. Treatment and clinical outcome data were available for 33 patients. Results: Most cases (n = 66, 87%) harbored at least one genomic alteration. EGFR and KRAS mutations were detected in 18 (24%) and 20 (26%) patients, respectively. No ALK alterations were found, but in two patients ROS1 translocation was identified. Of 22 cases tested, 17 were positive for PD-L1 staining. Octogenarian patients who received tyrosine kinase inhibitors (TKIs) based on molecular analysis showed clinical benefits, with long progression-free survival as expected in TKI-treated younger cohorts. Conclusions: This study highlights the utility of molecular profiling in all advanced-stage NSCLCs, regardless of the age at diagnosis, to drive personalized treatment. The prevalence of druggable alterations and the clinical benefits obtained by biologically-driven therapies in octogenarians were comparable to those of the younger NSCLC population. Full article
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Open AccessArticle Colorectal Cancer Prognosis Is Not Associated with BRAF and KRAS Mutations-A STROBE Compliant Study
J. Clin. Med. 2019, 8(1), 111; https://doi.org/10.3390/jcm8010111
Received: 26 December 2018 / Revised: 4 January 2019 / Accepted: 14 January 2019 / Published: 17 January 2019
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Abstract
Background: We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (BRAFV600E, henceforth BRAF) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and [...] Read more.
Background: We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (BRAFV600E, henceforth BRAF) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE39582) datasets. Materials and Methods: The effects of BRAF and KRAS mutations on overall survival (OS) and disease-free survival (DFS) of CRC were evaluated. Results: The mutational status of BRAF and KRAS genes was not associated with overall survival (OS) or DFS of the CRC patients drawn from the TCGA database. The 3-year OS and DFS rates of the BRAF mutation (+) vs. mutation (−) groups were 92.6% vs. 90.4% and 79.7% vs. 68.4%, respectively. The 3-year OS and DFS rates of the KRAS mutation (+) vs. mutation (−) groups were 90.4% vs. 90.5% and 65.3% vs. 73.5%, respectively. In stage II patients, however, the 3-year OS rate was lower in the BRAF mutation (+) group than in the mutation (−) group (85.5% vs. 97.7%, p < 0.001). The mutational status of BRAF genes of 497 CRC patients drawn from the GSE39582 database was not associated with OS or DFS. The 3-year OS and DFS rates of BRAF mutation (+) vs. mutation (−) groups were 75.7% vs. 78.9% and 73.6% vs. 71.1%, respectively. However, KRAS mutational status had an effect on 3-year OS rate (71.9% mutation (+) vs. 83% mutation (−), p = 0.05) and DFS rate (66.3% mutation (+) vs. 74.6% mutation (−), p = 0.013). Conclusions: We found no consistent association between the mutational status of BRAF nor KRAS and the OS and DFS of CRC patients from the TCGA and GSE39582 databases. Studies with longer-term records and larger patient numbers may be necessary to expound the influence of BRAF and KRAS mutations on the outcomes of CRC. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessArticle MiR-146a-5p Expression in Peripheral CD14+ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response
J. Clin. Med. 2019, 8(1), 110; https://doi.org/10.3390/jcm8010110
Received: 14 November 2018 / Revised: 12 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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Abstract
In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14+ monocytes and monocyte-derived [...] Read more.
In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14+ monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14+ monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14+ monocytes were cultured with media containing TNF-α and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14+ monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14+ monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14+ monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption. Full article
(This article belongs to the Section Dermatology)
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Open AccessArticle The Role of Continuous Glucose Monitoring, Diabetes Smartphone Applications, and Self-Care Behavior in Glycemic Control: Results of a Multi-National Online Survey
J. Clin. Med. 2019, 8(1), 109; https://doi.org/10.3390/jcm8010109
Received: 19 November 2018 / Revised: 10 January 2019 / Accepted: 14 January 2019 / Published: 17 January 2019
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Abstract
Background: This study investigated the determinants (with a special emphasis on the role of diabetes app use, use of continuous glucose monitoring (CGM) device, and self-care behavior) of glycemic control of type 1 and type 2 diabetes mellitus (DM). Methods: A web-based survey [...] Read more.
Background: This study investigated the determinants (with a special emphasis on the role of diabetes app use, use of continuous glucose monitoring (CGM) device, and self-care behavior) of glycemic control of type 1 and type 2 diabetes mellitus (DM). Methods: A web-based survey was conducted using diabetes Facebook groups, online patient-forums, and targeted Facebook advertisements (ads). Demographic, CGM, diabetes app use, and self-care behavior data were collected. Glycemic level data were categorized into hyperglycemia, hypoglycemia, and good control. Multinomial logistic regression stratified by diabetes type was performed. Results: The survey URL was posted in 78 Facebook groups and eight online forums, and ten targeted Facebook ads were conducted yielding 1854 responses. Of those owning smartphones (n = 1753, 95%), 1052 (62.6%) had type 1 and 630 (37.4%) had type 2 DM. More than half of the type 1 respondents (n = 549, 52.2%) and one third the respondents with type 2 DM (n = 210, 33.3%) reported using diabetes apps. Increased odds of experiencing hyperglycemia were noted in persons with type 1 DM with lower educational status (Adjusted Odds Ratio (AOR) = 1.7; 95% Confidence Interval (CI): 1.21–2.39); smokers (1.63, 95% CI: 1.15–2.32), and high diabetes self-management concern (AOR = 2.09, 95% CI: 1.15–2.32). CGM use (AOR = 0.66, 95% CI: 0.44–1.00); “general diet” (AOR = 0.86, 95% CI: 0.79–0.94); and “blood glucose monitoring” (AOR = 0.88, 95%CI: 0.80–0.97) self-care behavior reduced the odds of experiencing hyperglycemia. Hypoglycemia in type 1 DM was reduced by using CGM (AOR = 0.24, 95% CI: 0.09–0.60), while it was increased by experiencing a high diabetes self-management concern (AOR = 1.94, 95% CI: 1.04–3.61). Hyperglycemia in type 2 DM was increased by age (OR = 1.02, 95% CI: 1.00–1.04); high self-management concern (AOR = 2.59, 95% CI: 1.74–3.84); and poor confidence in self-management capacity (AOR = 3.22, 2.07–5.00). Conversely, diabetes app use (AOR = 0.63, 95% CI: 0.41–0.96) and “general diet” self-care (AOR = 0.84, 95% CI: 0.75–0.94), were significantly associated with the reduced odds of hyperglycemia. Conclusion: Diabetes apps, CGM, and educational interventions aimed at reducing self-management concerns and enhancing dietary self-care behavior and self-management confidence may help patients with diabetes to improve glycemic control. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessReview Deciphering the Molecular Profile of Lung Cancer: New Strategies for the Early Detection and Prognostic Stratification
J. Clin. Med. 2019, 8(1), 108; https://doi.org/10.3390/jcm8010108
Received: 30 November 2018 / Revised: 10 January 2019 / Accepted: 11 January 2019 / Published: 17 January 2019
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Abstract
Recent advances in radiological imaging and genomic analysis are profoundly changing the way to manage lung cancer patients. Screening programs which couple lung cancer risk prediction models and low-dose computed tomography (LDCT) recently showed their effectiveness in the early diagnosis of lung tumors. [...] Read more.
Recent advances in radiological imaging and genomic analysis are profoundly changing the way to manage lung cancer patients. Screening programs which couple lung cancer risk prediction models and low-dose computed tomography (LDCT) recently showed their effectiveness in the early diagnosis of lung tumors. In addition, the emerging field of radiomics is revolutionizing the approach to handle medical images, i.e., from a “simple” visual inspection to a high-throughput analysis of hundreds of quantitative features of images which can predict prognosis and therapy response. Yet, with the advent of next-generation sequencing (NGS) and the establishment of large genomic consortia, the whole mutational and transcriptomic profile of lung cancer has been unveiled and made publicly available via web services interfaces. This has tremendously accelerated the discovery of actionable mutations, as well as the identification of cancer biomarkers, which are pivotal for development of personalized targeted therapies. In this review, we will describe recent advances in cancer biomarkers discovery for early diagnosis, prognosis, and prediction of chemotherapy response. Full article
(This article belongs to the Special Issue Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis)
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Open AccessArticle Driving Type 2 Diabetes Risk Scores into Clinical Practice: Performance Analysis in Hospital Settings
J. Clin. Med. 2019, 8(1), 107; https://doi.org/10.3390/jcm8010107
Received: 22 December 2018 / Revised: 9 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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Abstract
Electronic health records and computational modelling have paved the way for the development of Type 2 Diabetes risk scores to identify subjects at high risk. Unfortunately, few risk scores have been externally validated, and their performance can be compromised when routine clinical data [...] Read more.
Electronic health records and computational modelling have paved the way for the development of Type 2 Diabetes risk scores to identify subjects at high risk. Unfortunately, few risk scores have been externally validated, and their performance can be compromised when routine clinical data is used. The aim of this study was to assess the performance of well-established risk scores for Type 2 Diabetes using routinely collected clinical data and to quantify their impact on the decision making process of endocrinologists. We tested six risk models that have been validated in external cohorts, as opposed to model development, on electronic health records collected from 2008-2015 from a population of 10,730 subjects. Unavailable or missing data in electronic health records was imputed using an existing validated Bayesian Network. Risk scores were assessed on the basis of statistical performance to differentiate between subjects who developed diabetes and those who did not. Eight endocrinologists provided clinical recommendations based on the risk score output. Due to inaccuracies and discrepancies regarding the exact date of Type 2 Diabetes onset, 76 subjects from the initial population were eligible for the study. Risk scores were useful for identifying subjects who developed diabetes (Framingham risk score yielded a c-statistic of 85%), however, our findings suggest that electronic health records are not prepared to massively use this type of risk scores. Use of a Bayesian Network was key for completion of the risk estimation and did not affect the risk score calculation (p > 0.05). Risk score estimation did not have a significant effect on the clinical recommendation except for starting pharmacological treatment (p = 0.004) and dietary counselling (p = 0.039). Despite their potential use, electronic health records should be carefully analyzed before the massive use of Type 2 Diabetes risk scores for the identification of high-risk subjects, and subsequent targeting of preventive actions. Full article
(This article belongs to the Special Issue The Future of Artificial Intelligence in Clinical Medicine)
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Open AccessArticle Effect of Size and Location of Nevi on Postoperative Pain and Emergence Agitation in Children Undergoing Nevi Excision
J. Clin. Med. 2019, 8(1), 106; https://doi.org/10.3390/jcm8010106
Received: 21 December 2018 / Revised: 15 January 2019 / Accepted: 16 January 2019 / Published: 17 January 2019
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Abstract
Congenital melanocytic nevi need surgical excisions. However, the effect of the size and location of the nevi on pain and emergence agitation have yet to be studied. The objective of this study was to evaluate (1) the ideal parameter of the nevus size [...] Read more.
Congenital melanocytic nevi need surgical excisions. However, the effect of the size and location of the nevi on pain and emergence agitation have yet to be studied. The objective of this study was to evaluate (1) the ideal parameter of the nevus size and (2) the effects of the size and location of the nevus on pain and emergence agitation. This observational study enrolled 100 children scheduled for an excision of a nevus under sevoflurane anesthesia. The parameters of the nevus size included the long diameter, the area before resection, the area of resection, and the proportion (the area of resection/total body surface). The nevus locations included the trunk, face, scalp, and extremities. The proportion of the nevi was the most ideal parameter in evaluating the pain and emergence agitation. A large size showed a higher emergence agitation than a small size (median (range); 6 (0–20) in small groups vs. 12.5 (0–20) in large groups, p = 0.021). However, the pain was comparable. The nevus location did not influence pain or emergence agitation. In a multivariate regression analysis, a younger age and an extensive excision were associated with higher pain and emergence agitation. In conclusion, large nevi induced more severe emergence agitation. However, the nevus location did not affect the outcome. In addition, a younger age was associated with pain and emergence agitation. Clinicians need to consider the proportion of nevi when managing children undergoing a nevus excision. Full article
(This article belongs to the Special Issue Management of Postoperative Pain)
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Open AccessArticle Righting the Misperceptions of Men Having Sex with Men: A Pre-Requisite for Protecting and Understanding Gender Incongruence in Vietnam
J. Clin. Med. 2019, 8(1), 105; https://doi.org/10.3390/jcm8010105
Received: 14 November 2018 / Revised: 10 January 2019 / Accepted: 14 January 2019 / Published: 17 January 2019
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Abstract
Protecting the rights of the lesbians, gays, bisexuals, transgender, intersex, and queers (LGBTIQ) population requires, first and foremost, a proper understanding of their sexual orientation and gender identity. This study highlights a severe misunderstanding and lack of knowledge among health professionals in Vietnam [...] Read more.
Protecting the rights of the lesbians, gays, bisexuals, transgender, intersex, and queers (LGBTIQ) population requires, first and foremost, a proper understanding of their sexual orientation and gender identity. This study highlights a severe misunderstanding and lack of knowledge among health professionals in Vietnam with regard to the men who have sex with men (MSM) and transgenders. This study uses (i) a survey based on the convenience sampling method among 150 health workers that covered 61 questions and (ii) 12 in-depth interviews in two metropolitan centres in Vietnam, Hanoi and Ho Chi Minh city. Three main topics are explored: (i) the general knowledge of healthcare workers about MSM and transgenders; (ii) their knowledge about the sexual reproductive health and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) risks of MSM and transgenders; and (iii) their attitudes and behaviors towards MSM and transgenders. One of the notable findings is how prevalent the misperceptions are across the board, namely, in staff of both sexes, in both cities, at various kinds of medical facilities, at different work positions and educational levels. Half of the respondents consider transgenders to have a curable mental problem while 45% say MSM only have sex with males. Most remarkably, 12.7% state if they have any choice, they want nothing to do with MSM and transgenders. The study finds there is a considerable percentage of health professionals who lack knowledge about the diversity of sexual orientation, gender identity, and health issues related to the sexual minorities and gender non-conforming population. To improve the clinical process for serving these at-risk groups, the study suggests the continual education for the health workers needs to be added to their formal as well as in-job training. Full article
(This article belongs to the Special Issue Novel Research in Gender Incongruence)
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Open AccessArticle Clopidogrel versus Ticagrelor for Secondary Prevention after Coronary Artery Bypass Grafting
J. Clin. Med. 2019, 8(1), 104; https://doi.org/10.3390/jcm8010104
Received: 8 December 2018 / Revised: 2 January 2019 / Accepted: 14 January 2019 / Published: 17 January 2019
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Abstract
We sought to evaluate the outcomes of postoperative three-month dual antiplatelet therapy in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) following off-pump coronary artery bypass grafting (OPCAB) with exclusively arterial grafts. Between 2013–2016, dual antiplatelet therapy (DAPT) with either aspirin + clopidogrel (ASA [...] Read more.
We sought to evaluate the outcomes of postoperative three-month dual antiplatelet therapy in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) following off-pump coronary artery bypass grafting (OPCAB) with exclusively arterial grafts. Between 2013–2016, dual antiplatelet therapy (DAPT) with either aspirin + clopidogrel (ASA + CPD group, n = 100) or aspirin + ticagrelor (ASA + TCG group, n = 169) was prescribed postoperatively in 269 NSTE-ACS patients after total arterial OPCAB. Patients with indications for other oral anticoagulants were excluded from the study. Three-month DAPT was completed in 259 patients (96%); ASA + CPD group (n = 94) vs. ASA + TCG group (n = 165). A one-to-one propensity score matching was performed. Unadjusted comparison between the groups showed no significant difference in overall survival (P = 0.253) and composite outcome of major adverse cerebrovascular and cardiovascular event (MACCE) and major bleeding (P = 0.276). The rate of freedom from composite outcome at one year in the ASA + CPD and ASA + TCG groups was 91 ± 3% and 93 ± 2%, respectively. In multivariable analysis, being in the ASA + TCG group did not increase the risk of the composite outcome of MACCE and major bleeding (P = 0.972, hazard ratio: 1.0, 95% confidence interval: 0.4–2.3). Propensity score-matched comparison (76 pairs) showed no significant difference in the overall survival (P = 0.423) and composite outcome between the groups (P = 0.442). In the setting of exclusive arterial grafting, post-OPCAB three-month DAPT showed acceptable outcomes in patients with NSTE-ACS. There was no significant difference in overall survival or composite outcome of MACCE and major bleeding between the ASA + CPD and ASA + TCG groups. Full article
(This article belongs to the Section Cardiology)
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Open AccessArticle Increased Circulating VAP-1 Levels Are Associated with Liver Fibrosis in Chronic Hepatitis C Infection
J. Clin. Med. 2019, 8(1), 103; https://doi.org/10.3390/jcm8010103
Received: 25 November 2018 / Revised: 7 January 2019 / Accepted: 9 January 2019 / Published: 17 January 2019
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Abstract
Vascular adhesion protein-1 (VAP-1) is a multifunction protein. While membrane-bound VAP-1 is an adhesion protein, soluble VAP-1 catalyzes the deamination of primary amines through its semicarbazide-sensitive amino oxidase (SSAO) activity. VAP-1 supports the transmigration of leukocytes and increases oxidative stress. In chronic liver [...] Read more.
Vascular adhesion protein-1 (VAP-1) is a multifunction protein. While membrane-bound VAP-1 is an adhesion protein, soluble VAP-1 catalyzes the deamination of primary amines through its semicarbazide-sensitive amino oxidase (SSAO) activity. VAP-1 supports the transmigration of leukocytes and increases oxidative stress. In chronic liver diseases, it plays a role in leukocyte infiltration and fibrogenesis. Here, we measured VAP-1 plasma concentration and its SSAO activity in 322 patients with chronic hepatitis C infection and evaluated the association of VAP-1 with fibrosis stages. VAP-1 concentration strongly correlated with liver stiffness and was the second strongest influencing variable after gamma-glutamytransferase (GGT) for liver stiffness in regression analysis. The VAP-1 concentration increased with advancing fibrosis stages and the highest concentrations were found in patients with cirrhosis. According to the receiver operating characteristic (ROC) analysis, a VAP-1 cut-off value of 541 ng/mL predicted histologically confirmed cirrhosis (sensitivity 74%; specificity 72%). SSAO activity correlated only moderately with liver stiffness, showing a relatively small increase in advanced fibrosis. To our knowledge, this is the first study on VAP-1 in chronic hepatitis C infection showing its association with progressive fibrosis. In conclusion, VAP-1 plasma concentration, rather than its SSAO activity, may represent a non-invasive biomarker for monitoring fibrogenesis in patients with chronic hepatitis C infection. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessArticle Risk Factors and Outcomes of Recurrent Candidemia in Children: Relapse or Re-Infection?
J. Clin. Med. 2019, 8(1), 99; https://doi.org/10.3390/jcm8010099
Received: 14 December 2018 / Revised: 7 January 2019 / Accepted: 11 January 2019 / Published: 16 January 2019
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Abstract
In this paper, our aim was to investigate the incidence, clinical characteristics, risk factors, and outcomes of recurrent candidemia in children. We retrospectively reviewed all children with candidemia from a medical center in Taiwan between 2004 and 2015. Two episodes of candidemia ≥30 [...] Read more.
In this paper, our aim was to investigate the incidence, clinical characteristics, risk factors, and outcomes of recurrent candidemia in children. We retrospectively reviewed all children with candidemia from a medical center in Taiwan between 2004 and 2015. Two episodes of candidemia ≥30 days apart with clinical and microbiological resolution in the interim were defined as “late recurrence”, and those that had 8–29 days apart from previous episodes were defined as “early recurrence”. 45 patients (17.2%) had 57 episodes of recurrent candidemia, and 24 had 28 episodes of late recurrent candidemia. The median time between recurrences was 1.8 months (range: <1 month to 13 months). Of those, 29 had relapsed candidemia and 28 were re-infected by different Candida species (n = 24) or by different strains (n = 4). Recurrent candidemia patients were more likely to require echinocandins treatment, had a longer duration of candidemia, and higher rate of treatment failure (p = 0.001, 0.014, and 0.012, respectively). Underlying gastrointestinal diseases (Odds ratio (OR) 3.84; 95% Confidence interval (CI) 1.81–8.12) and neurological sequelae (OR 2.32; 95% CI 1.15–4.69) were independently associated with the development of recurrent candidemia. 17.2% of pediatric patients with candidemia developed recurrent candidemia, and approximately half were re-infected. Underlying gastrointestinal diseases and neurological sequelae were the independent risk factors for recurrent candidemia. Full article
(This article belongs to the Section Microbiology & Parasitology)
Open AccessReview Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease
J. Clin. Med. 2019, 8(1), 98; https://doi.org/10.3390/jcm8010098
Received: 25 November 2018 / Revised: 30 December 2018 / Accepted: 11 January 2019 / Published: 16 January 2019
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Abstract
Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current [...] Read more.
Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current therapy does not consider the sexual dimorphism; i.e., differences in anatomical structures and metabolism of tissues. Here, we discuss how genetic, epigenetic, hormonal, cellular or molecular factors may explain the different CVD risk, especially in high-risk groups such as women with diabetes. We analyze whether sex may modify the effects of diabetes at risk of CAD. Finally, we discuss current diagnostic techniques in the evaluation of CAD and IHD in diabetic women. Full article
(This article belongs to the Section Cardiology)
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Open AccessArticle Thirty-Day Postoperative Outcomes Following Sugammadex Use in Colorectal Surgery Patients: Retrospective Study
J. Clin. Med. 2019, 8(1), 97; https://doi.org/10.3390/jcm8010097
Received: 15 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 16 January 2019
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Abstract
Purpose: Sugammadex rapidly reverses muscle relaxation compared to acetylcholinesterase inhibitors. The long-term outcomes of sugammadex, however, are not well known. We compared 30-day postoperative outcomes following sugammadex and acetylcholinesterase inhibitor use in colorectal surgery patients. Patients and methods: Colorectal surgical patients older than [...] Read more.
Purpose: Sugammadex rapidly reverses muscle relaxation compared to acetylcholinesterase inhibitors. The long-term outcomes of sugammadex, however, are not well known. We compared 30-day postoperative outcomes following sugammadex and acetylcholinesterase inhibitor use in colorectal surgery patients. Patients and methods: Colorectal surgical patients older than 21 were included in this retrospective study, and were dichotomized according to use of reversal agents, sugammadex (group S), and acetylcholinesterase inhibitor (group A). We assessed 30-day postoperative outcomes, including total length of hospital stay, length of postoperative hospital stay, readmission rate, and delayed discharge rate. Additional parameters included postanesthetic care unit stay time, time to first successful oral intake, unforeseen intensive care unit (ICU) admission rate, postoperative pulmonary complications, and mortality. Results: Among a total of 585 patients, 157 patients remained in each group after propensity score matching. Total length of hospital stay, length of postoperative hospital stay, and readmission rates did not differ between the two groups, while the incidence of delayed discharge was significantly lower in group S (23 (15%) vs. 40 (25%), p = 0.017). Other outcomes did not differ between the two groups. Conclusion: We found no difference in 30-day postoperative outcomes following sugammadex and acetylcholinesterase inhibitor use. The only difference between these treatments was the associated incidence of delayed discharge, which was lower in group S. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
Open AccessArticle Early Vitamin C and Thiamine Administration to Patients with Septic Shock in Emergency Departments: Propensity Score-Based Analysis of a Before-and-After Cohort Study
J. Clin. Med. 2019, 8(1), 102; https://doi.org/10.3390/jcm8010102
Received: 16 December 2018 / Revised: 10 January 2019 / Accepted: 11 January 2019 / Published: 16 January 2019
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Abstract
Background: Intravenous vitamin C and thiamine administration may be a potential adjuvant therapy for septic shock. We aimed to investigate the impact of early vitamin C and thiamine administration in septic shock patients. Methods: This retrospective before-and-after cohort study used data extracted from [...] Read more.
Background: Intravenous vitamin C and thiamine administration may be a potential adjuvant therapy for septic shock. We aimed to investigate the impact of early vitamin C and thiamine administration in septic shock patients. Methods: This retrospective before-and-after cohort study used data extracted from the Korean Shock Society’s prospective septic shock registry. We compared 28-day and in-hospital mortality rates between patients treated with intravenous vitamin C (3 g/12 h or 1.5 g/6 h) and thiamine (200 mg/12 h) <6 h after shock recognition from July through December 2017 (n = 229) and control patients from October 2015 through June 2017 (n = 915) using propensity score matching. Results: The 28-day (18.3% vs. 17.5%; p = 0.76) and in-hospital (16.6% vs. 18.3%; p = 0.55) mortality rates did not differ between treatment and control groups, nor did 28-day (18.5% vs. 17.5%; p = 0.84) and in-hospital (16.7% vs. 18.4%; p = 0.54) mortality rates after matching. In the subgroup analysis, treatment was associated with lower in-hospital mortality rates in patients with albumin <3.0 mg/dL or a Sequential Organ Failure Assessment (SOFA) score >10. Conclusion: Early vitamin C and thiamine administration in patients with septic shock did not improve survival; however, administration could benefit conditions that are more severe, such as hypoalbuminemia or severe organ failure. Full article
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Open AccessReview Sinonasal-Related Orbital Infections in Children: A Clinical and Therapeutic Overview
J. Clin. Med. 2019, 8(1), 101; https://doi.org/10.3390/jcm8010101
Received: 7 December 2018 / Revised: 9 January 2019 / Accepted: 14 January 2019 / Published: 16 January 2019
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Abstract
Sinonasal-related orbital infections (SROIs) are typically pediatric diseases that occur in 3–4% of children with acute rhinosinusitis. They are characterised by various clinical manifestations, such as peri-orbital and orbital cellulitis or orbital and sub-periosteal abscesses that may develop anteriorly or posteriorly to the [...] Read more.
Sinonasal-related orbital infections (SROIs) are typically pediatric diseases that occur in 3–4% of children with acute rhinosinusitis. They are characterised by various clinical manifestations, such as peri-orbital and orbital cellulitis or orbital and sub-periosteal abscesses that may develop anteriorly or posteriorly to the orbital septum. Posterior septal complications are particularly dangerous, as they may lead to visual loss and life-threatening events, such as an intracranial abscess and cavernous sinus thrombosis. Given the possible risk of permanent visual loss due to optic neuritis or orbital nerve ischemia, SROIs are considered ophthalmic emergencies that need to be promptly recognised and treated in an urgent-care setting. The key to obtaining better clinical outcomes in children with SROIs is a multi-disciplinary assessment by pediatricians, otolaryngologists, ophthalmologists, radiologists, and in selected cases, neurosurgeons, neurologists, and infectious disease specialists. The aim of this paper is to provide an overview of the pathogenesis, clinical manifestations, diagnosis, and treatment of pediatric SROIs, and to make some practical recommendations for attending clinicians. Full article
(This article belongs to the Special Issue Pediatric Rhinosinusitis and Asthma)
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J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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