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J. Clin. Med., Volume 9, Issue 8 (August 2020) – 360 articles

Cover Story (view full-size image): Mitochondrial dysfunction is emerging as an important contributory factor to the pathophysiology of lysosomal storage disorders (LSDs). The cause of mitochondrial dysfunction in LSDs appears to be multifactorial, although impaired mitophagy and oxidative stress appear to be common inhibitory mechanisms shared amongst these heterogeneous disorders. Once impaired, dysfunctional mitochondria may impact upon the function of the lysosome by the generation of reactive oxygen species as well as depriving the lysosome of ATP which is required by the V-ATPase proton pump to maintain the acidity of the lumen. In this review we examine the putative mechanisms that may be responsible for mitochondrial dysfunction in reported LSDs which will be supplemented with morphological and clinical information. View this paper.
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Review
Application of Anti-Inflammatory Agents in Prostate Cancer
J. Clin. Med. 2020, 9(8), 2680; https://doi.org/10.3390/jcm9082680 - 18 Aug 2020
Cited by 9 | Viewed by 2195
Abstract
Chronic inflammation is a major cause of human cancers. The environmental factors, such as microbiome, dietary components, and obesity, provoke chronic inflammation in the prostate, which promotes cancer development and progression. Crosstalk between immune cells and cancer cells enhances the secretion of intercellular [...] Read more.
Chronic inflammation is a major cause of human cancers. The environmental factors, such as microbiome, dietary components, and obesity, provoke chronic inflammation in the prostate, which promotes cancer development and progression. Crosstalk between immune cells and cancer cells enhances the secretion of intercellular signaling molecules, such as cytokines and chemokines, thereby orchestrating the generation of inflammatory microenvironment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play pivotal roles in inflammation-associated cancer by inhibiting effective anti-tumor immunity. Anti-inflammatory agents, such as aspirin, metformin, and statins, have potential application in chemoprevention of prostate cancer. Furthermore, pro-inflammatory immunity-targeted therapies may provide novel strategies to treat patients with cancer. Thus, anti-inflammatory agents are expected to suppress the “vicious cycle” created by immune and cancer cells and inhibit cancer progression. This review has explored the immune cells that facilitate prostate cancer development and progression, with particular focus on the application of anti-inflammatory agents for both chemoprevention and therapeutic approach in prostate cancer. Full article
(This article belongs to the Special Issue The Application of Anti-inflammatory Agents in Prostate Cancer)
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Review
Management of Acute Kidney Injury Following Major Abdominal Surgery: A Contemporary Review
J. Clin. Med. 2020, 9(8), 2679; https://doi.org/10.3390/jcm9082679 - 18 Aug 2020
Cited by 3 | Viewed by 1426
Abstract
Acute kidney injury (AKI) is a frequent occurrence following major abdominal surgery and is independently associated with both in-hospital and long-term mortality, as well as with a higher risk of progressing to chronic kidney disease (CKD) and cardiovascular events. Postoperative AKI can account [...] Read more.
Acute kidney injury (AKI) is a frequent occurrence following major abdominal surgery and is independently associated with both in-hospital and long-term mortality, as well as with a higher risk of progressing to chronic kidney disease (CKD) and cardiovascular events. Postoperative AKI can account for up to 40% of in-hospital AKI cases. Given the differences in patient characteristics and the pathophysiology of postoperative AKI, it is inappropriate to assume that the management after noncardiac and nonvascular surgery are the same as those after cardiac and vascular surgery. This article provides a comprehensive review on the available evidence on the management of postoperative AKI in the setting of major abdominal surgery. Full article
(This article belongs to the Special Issue Prevention and Treatment of Acute Kidney Injury)
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Article
Difference in Pupillary Diameter as an Important Factor for Evaluating Amplitude of Accommodation: A Prospective Observational Study
J. Clin. Med. 2020, 9(8), 2678; https://doi.org/10.3390/jcm9082678 - 18 Aug 2020
Cited by 7 | Viewed by 1078
Abstract
Presbyopia is increasing globally due to aging and the widespread use of visual display terminals. Presbyopia is a decrease in the eye’s amplitude of accommodation (AA) due to loss of crystalline lens elasticity. AA differs widely among individuals. We aimed to determine the [...] Read more.
Presbyopia is increasing globally due to aging and the widespread use of visual display terminals. Presbyopia is a decrease in the eye’s amplitude of accommodation (AA) due to loss of crystalline lens elasticity. AA differs widely among individuals. We aimed to determine the factors that cause presbyopia, other than advanced age, for early medical intervention. We examined 95 eyes of 95 healthy volunteers (33 men, 62 women) aged 22–62 years (mean: 37.22 ± 9.77 years) with a corrected visual acuity of ≥1.0 and without other eye afflictions except ametropia. Subjective refraction, AA, maximum and minimum pupillary diameters during accommodation, axial length of the eye, and crystalline lens thickness were measured. AA was measured using an auto refractometer/keratometer/tonometer/pachymeter. The difference between maximum and minimum pupillary diameters was calculated. On multiple regression analysis, age and difference in pupillary diameter were both significantly and independently associated with AA in participants aged <44 years, but not in those aged ≥45 years. Our results suggest that the difference in pupillary diameter could be an important age-independent factor for evaluating AA in healthy individuals without cataract. Thus, improving the difference in pupillary diameter values could be an early treatment target for presbyopia. Full article
(This article belongs to the Special Issue Ophthalmic Optics and Visual Function)
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Article
Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration
J. Clin. Med. 2020, 9(8), 2677; https://doi.org/10.3390/jcm9082677 - 18 Aug 2020
Cited by 3 | Viewed by 919
Abstract
Background: To evaluate macular perfusion in patients with Von Hippel–Lindau (VHL) disease. Methods: VHL patients with or without peripheral retinal hemangioblastomas (RHs) were consecutively enrolled. A group of healthy subjects served as controls. Macular perfusion was analyzed by means of OCT angiography (OCTA) [...] Read more.
Background: To evaluate macular perfusion in patients with Von Hippel–Lindau (VHL) disease. Methods: VHL patients with or without peripheral retinal hemangioblastomas (RHs) were consecutively enrolled. A group of healthy subjects served as controls. Macular perfusion was analyzed by means of OCT angiography (OCTA) in the superficial vascular plexus (SVP), and in the intermediate (ICP) and deep retinal capillary (DCP) plexuses. The following OCTA parameters were measured: Vessel Area Density (VAD), Vessel Length Fraction (VLF), Vessel Diameter Index (VDI) and Fractal Dimension (FD). Results: Sixty-three VHL patients (113 eyes) and 28 healthy controls (56 eyes) were enrolled. All OCTA quantitative parameters were reduced in VHL patients vs. controls, reaching statistical significance for VAD of the SVP (0.348 ± 0.07 vs. 0.369 ± 0.06, p = 0.0368) and VDI of all plexuses (p < 0.03 for all). No significant differences were detected between eyes without or with peripheral RHs. Conclusions: Macular perfusion is reduced in VHL patients demonstrating retinal vessel changes that are independent of the presence of peripheral RHs. VHL gene mutations disrupt the hypoxia-induced (HIF)/vascular endothelium growth factors (VEGF) pathway and the Notch signaling, both essential for the normal retinal vasculogenesis and angiogenesis. Therefore, an anomalous generalized retinal vascular development may be hypothesized in VHL disease. Full article
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Article
Scores of Health-Related Quality of Life Questionnaire Worsen Consistently in Patients of COPD: Estimating Disease Progression over 30 Years by SReFT with Individual Data Collected in SUMMIT Trial
J. Clin. Med. 2020, 9(8), 2676; https://doi.org/10.3390/jcm9082676 - 18 Aug 2020
Viewed by 1780
Abstract
The aim of this study was to elucidate the lifelong disease progression of chronic obstructive pulmonary disease (COPD) with biomarker changes and identify their influencing factors, by utilizing a new analysis method, Statistical Restoration of Fragmented Time-course (SReFT). Individual patient data (n [...] Read more.
The aim of this study was to elucidate the lifelong disease progression of chronic obstructive pulmonary disease (COPD) with biomarker changes and identify their influencing factors, by utilizing a new analysis method, Statistical Restoration of Fragmented Time-course (SReFT). Individual patient data (n = 1025) participating in the Study to Understand Mortality and MorbidITy (SUMMIT, NCT01313676), which was collected within the observational period of 4 years, were analyzed. The SReFT analysis suggested that scores of St. George’s Respiratory Questionnaire and COPD assessment test, representative scores of the health-related quality of life (HRQOL) questionnaire, increased consistently for 30 years of disease progression, which was not detected by conventional analysis with a linear mixed effect model. It was estimated by the SReFT analysis that normalized forced expiratory volume in one second for age, sex, and body size (%FEV1) reduced for the initial 10 years from the onset of the disease but thereafter remained constant. The analysis of HRQOL scores and lung functions suggested that smoking cessation slowed COPD progression by approximately half and that exacerbation accelerated it considerably. In conclusion, this retrospective study utilizing SReFT elucidated the progression of COPD over 30 years and associated quantitative changes in the HRQOL scores and lung functions. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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Review
Applications of the Amniotic Membrane in Vitreoretinal Surgery
J. Clin. Med. 2020, 9(8), 2675; https://doi.org/10.3390/jcm9082675 - 18 Aug 2020
Cited by 1 | Viewed by 1124
Abstract
Recently, the use of the human amniotic membrane (hAM) has been extended to treat retinal disorders, such as macular holes that failed to close and retinal tears. The hAM has demonstrated the induction of a recovery process of the external retinal layers involving [...] Read more.
Recently, the use of the human amniotic membrane (hAM) has been extended to treat retinal disorders, such as macular holes that failed to close and retinal tears. The hAM has demonstrated the induction of a recovery process of the external retinal layers involving the external limiting membrane (ELM) and the ellipsoid zone (EZ). After that, the application of the hAM for retinal pathologies was extended to large macular tears, high myopic retinal detachment associated with MH, paravascular tears, serous macular detachment associated with optic pit, complicated retinal detachment and advanced age-related macular degeneration (AMD). The hAM has shown a potential in repairing retinal tissue through a regeneration process. This review aims to highlight the use of the hAM in various vitreo-retinal surgical fields, and to confront it with other cutting-edge surgical techniques used to treat challenging vitreo-retinal pathologies. Full article
(This article belongs to the Special Issue Updates in Ocular Surgery)
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Article
Comparative Analysis of Blood and Bone Marrow for the Detection of Circulating and Disseminated Tumor Cells and Their Prognostic and Predictive Value in Esophageal Cancer Patients
J. Clin. Med. 2020, 9(8), 2674; https://doi.org/10.3390/jcm9082674 - 18 Aug 2020
Cited by 1 | Viewed by 884
Abstract
Hematogenic tumor cell spread is a key event in metastasis. However, the clinical significance of circulating tumor cells (CTC) in the blood and disseminated tumor cells (DTC) in bone marrow is still not fully understood. Here, the presence of DTC and CTC in [...] Read more.
Hematogenic tumor cell spread is a key event in metastasis. However, the clinical significance of circulating tumor cells (CTC) in the blood and disseminated tumor cells (DTC) in bone marrow is still not fully understood. Here, the presence of DTC and CTC in esophageal cancer (EC) patients and its correlation with clinical parameters was investigated to evaluate the CTC/DTC prognostic value in EC. This study included 77 EC patients with complete surgical tumor resection. CTC and DTC were analyzed in blood and bone marrow using nested CK20 reverse transcription-nested polymerase chain reaction (RT-PCR) and findings were correlated with clinical data. Twenty-seven of 76 patients (36.5%) showed CK20 positivity in the blood, 19 of 61 patients (31.1%) in bone marrow, and 40 (51.9%) of 77 patients were positive in either blood or bone marrow or both. In multivariate analyses, only the DTC status emerged as independent predictor of overall and tumor specific survival. Our study revealed that, while the presence of CTC in blood is not associated with a worse prognosis, DTC detection in the bone marrow is a highly specific and independent prognostic marker in EC patients. Larger cohort studies could unravel how this finding can be translated into improved therapy management in EC. Full article
(This article belongs to the Special Issue New Treatments for Esophageal Diseases)
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Optimal Antithrombotic Treatment of Patients with Atrial Fibrillation Early after an Acute Coronary Syndrome—Triple Therapy, Dual Antithrombotic Therapy with an Anticoagulant… Or, Rather, Temporary Dual Antiplatelet Therapy?
J. Clin. Med. 2020, 9(8), 2673; https://doi.org/10.3390/jcm9082673 - 18 Aug 2020
Cited by 6 | Viewed by 1163
Abstract
The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic [...] Read more.
The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic therapy with an anticoagulant (DAT) likely provides only suboptimal coronary protection early after stent implantation. Moreover, TAT precludes the advantages provided by the use of the latest and more potent P2Y12 inhibitors in ACS patients. Here, we aimed to simulate and compare the expected coronary, cardioembolic, and hemorrhagic outcomes offered by DAT, TAT, or modern dual antiplatelet therapy (DAPT) with aspirin plus one of the latest P2Y12 inhibitors in AF patients early after an ACS. The comparison of numbers needed to treat to prevent major adverse events with the various antithrombotic regimens suggests that AF–ACS patients at high ischemic and hemorrhagic risk and at moderately low embolic risk (CHA2DS2VASc score 2–4) might safely withhold anticoagulation after revascularization for one month taking advantage of a modern DAPT, with a favorable risk-to-benefit ratio. In conclusion, this strategy, not sufficiently addressed in recent European and North American guidelines or consensus documents, adds to the spectrum of treatment options in these difficult patients; it might be the best choice in a substantial number of patients; and should be prospectively tested in a randomized controlled trial. Full article
(This article belongs to the Special Issue Antithrombotic Treatment of Acute Coronary Syndrome)
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Article
Corneal Epithelial Toxicity after Intravitreal Methotrexate Injection for Vitreoretinal Lymphoma: Clinical and In Vitro Studies
J. Clin. Med. 2020, 9(8), 2672; https://doi.org/10.3390/jcm9082672 - 18 Aug 2020
Cited by 8 | Viewed by 1231
Abstract
Methotrexate is widely used as an intraocular chemotherapy for vitreoretinal lymphoma (VRL). Although corneal toxicity has been reported in patients after intravitreal methotrexate injections, the incidence, outcome, and mechanism of the toxicity are unclear. Herein, we performed a clinical study to evaluate the [...] Read more.
Methotrexate is widely used as an intraocular chemotherapy for vitreoretinal lymphoma (VRL). Although corneal toxicity has been reported in patients after intravitreal methotrexate injections, the incidence, outcome, and mechanism of the toxicity are unclear. Herein, we performed a clinical study to evaluate the incidence, predisposing factors, and treatment outcome of corneal epitheliopathy associated with intravitreal methotrexate injection. In addition, we directly investigated cytotoxic effects and mechanisms of methotrexate in cultures of human corneal epithelial cells (CECs). Medical chart reviews revealed that corneal epitheliopathy occurred in 15 eyes (22.7%, 12 patients) out of 66 eyes (45 patients) after intravitreal methotrexate injections for treatment of VRL. The use of topical anti-glaucoma medication was significantly associated with development of corneal epitheliopathy. The epitheliopathy resolved in all patients 2.4 months after onset. In culture, methotrexate decreased the survival of CECs by inducing apoptosis, increasing oxidative stress, suppressing proliferation, and upregulating inflammatory cytokines. The addition of folinic acid significantly protected the cells from the methotrexate-induced toxicity. Hence, our results suggest that care should be taken to minimize the contact of methotrexate with corneal epithelium during injection, and folic or folinic acid supplementation might be beneficial for preventing corneal complications in patients undergoing intravitreal methotrexate injections. Full article
(This article belongs to the Section Ophthalmology)
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Article
A Novel Technique of Endoscopic Papillectomy with Hybrid Endoscopic Submucosal Dissection for Ampullary Tumors: A Proof-of-Concept Study (with Video)
J. Clin. Med. 2020, 9(8), 2671; https://doi.org/10.3390/jcm9082671 - 18 Aug 2020
Cited by 2 | Viewed by 1028
Abstract
Background: Endoscopic papillectomy (EP) carries a potential risk of procedure-related adverse events and incomplete resection. Since hybrid endoscopic submucosal dissection (ESD) had been established as an alternative option for relatively large and difficult gastrointestinal tumors, we evaluated a novel EP with hybrid ESD [...] Read more.
Background: Endoscopic papillectomy (EP) carries a potential risk of procedure-related adverse events and incomplete resection. Since hybrid endoscopic submucosal dissection (ESD) had been established as an alternative option for relatively large and difficult gastrointestinal tumors, we evaluated a novel EP with hybrid ESD (hybrid ESD-EP) for curative safe margin in this proof-of-concept study. Methods: A total of eight cases who underwent hybrid ESD-EP between 2018 and 2020 were identified from our prospectively maintained database. Hybrid ESD-EP involved a (sub)circumferential incision with partial submucosal dissection, and subsequent snare resection of ampullary tumors, which was performed by two endoscopists with expertise in ESD or endoscopic retrograde cholangiopancreatography. Demographic data and clinicopathological outcomes were retrospectively evaluated. Results: En bloc resection was achieved by hybrid ESD-EP in all eight cases, with the median procedure time of 112 (range: 65–170) minutes. The median diameters of the resected specimens and tumors were 18 and 12 mm, respectively. All lateral margins were clear, whereas vertical margin was uncertain in three (38%), resulting in the complete resection rate of 63%. Postoperative bleeding and pancreatitis developed in each one (13%). No tumor recurrence was observed even in those cases with uncertain vertical margin, after a median follow-up of 244 (range, 97–678) days. Conclusions: Hybrid ESD-EP seems to be feasible and promising in ensuring the lateral resection margin. However, further investigations, especially to secure the vertical margin and to shorten the procedure time, should be required. Full article
(This article belongs to the Special Issue Pancreato-Biliary Interventional Endoscopy)
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Review
Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease
J. Clin. Med. 2020, 9(8), 2670; https://doi.org/10.3390/jcm9082670 - 18 Aug 2020
Cited by 7 | Viewed by 1952
Abstract
Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression [...] Read more.
Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD. Full article
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Article
Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity
J. Clin. Med. 2020, 9(8), 2669; https://doi.org/10.3390/jcm9082669 - 18 Aug 2020
Cited by 8 | Viewed by 1134
Abstract
Background: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. Methods: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species [...] Read more.
Background: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. Methods: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species (TAC-ROS), and superoxide dismutase (SOD)), absolute telomere length (aTL), and apoptosis (DNA fragmentation) in peripheral blood samples of a hospital-based population of PP. Associations of these biomarkers to sarcopenia, frailty, functional status, and 12-month mortality were analyzed. Results: Of the 444 recruited patients, 97 (21.8%), 278 (62.6%), and 80 (18%) were sarcopenic, frail, or both, respectively. Oxidative stress markers (lower TAC-ROS and higher SOD) were significantly enhanced and aTL significantly shortened in patients with sarcopenia, frailty or both syndromes. No evidence of apoptosis was detected in blood leukocytes of any of the patients. Both oxidative stress markers (GR, p = 0.04) and telomere shortening (p = 0.001) were associated to death risk and to less survival days. Conclusions: Oxidative stress markers and telomere length were enhanced and shortened, respectively, in blood samples of polypathological patients with sarcopenia and/or frailty. Both were associated to decreased survival. They could be useful in the clinical practice to assess vulnerable populations with multimorbidity and of potential interest as therapeutic targets. Full article
(This article belongs to the Special Issue Prevention and Treatment of Sarcopenia)
Article
Alcohol Induced Depression: Clinical, Biological and Genetic Features
J. Clin. Med. 2020, 9(8), 2668; https://doi.org/10.3390/jcm9082668 - 18 Aug 2020
Cited by 3 | Viewed by 1434
Abstract
Background: In clinical practice, there is the need to have clinical and biological markers to identify induced depression. The objective was to investigate clinical, biological and genetic differences between Primary Major Depression (Primary MD) and Alcohol Induced MD (AI-MD). Methods: Patients, of both [...] Read more.
Background: In clinical practice, there is the need to have clinical and biological markers to identify induced depression. The objective was to investigate clinical, biological and genetic differences between Primary Major Depression (Primary MD) and Alcohol Induced MD (AI-MD). Methods: Patients, of both genders, were recruited from psychiatric hospitalisation units. The PRISM instrument was used to establish the diagnoses. Data on socio-demographic/family history, clinical scales for depression, anxiety, personality and stressful life events were recorded. A blood test was performed analysing biochemical parameters and a Genome Wide Association Study (GWAS) to identify genetic markers associated with AI-MD. Results: A total of 80 patients were included (47 Primary MD and 33 AI-MD). The AI-MD group presented more medical comorbidities and less family history of depression. There were differences in traumatic life events, with higher scores in the AI-MD (14.21 ± 11.35 vs. 9.30 ± 7.38; p = 0.021). DSM-5 criteria were different between groups with higher prevalence of weight changes and less anhedonia, difficulties in concentration and suicidal thoughts in the AI-MD. None of the genetic variants reached significance beyond multiple testing thresholds; however, some suggestive variants were observed. Conclusions: This study has found clinical and biological features that may help physicians to identify AI-MD and improve its therapeutic approach. Full article
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Article
Prediction of Long-Term Outcomes in ST-Elevation Myocardial Infarction and Non-ST Elevation Myocardial Infarction with and without Creatinine Kinase Elevation—Post-Hoc Analysis of the J-MINUET Study
J. Clin. Med. 2020, 9(8), 2667; https://doi.org/10.3390/jcm9082667 - 18 Aug 2020
Cited by 2 | Viewed by 1016
Abstract
Background: A Japanese prospective, nation-wide, multicenter registry (J-MINUET) showed that long-term outcomes were worse in non-ST elevation acute myocardial infarction (NSTEMI), diagnosed by increased cardiac troponin levels, compared to STEMI. This was observed in both non-STEMI with elevated creatine kinase (CK) (NSTEMI+CK) and [...] Read more.
Background: A Japanese prospective, nation-wide, multicenter registry (J-MINUET) showed that long-term outcomes were worse in non-ST elevation acute myocardial infarction (NSTEMI), diagnosed by increased cardiac troponin levels, compared to STEMI. This was observed in both non-STEMI with elevated creatine kinase (CK) (NSTEMI+CK) and non-STEMI without elevated CK (NSTEMI-CK). However, predictive factors for long-term outcomes in STEMI, NSTEMI+CK, and NSTEMI-CK have not been elucidated. Methods: Using the Cox proportional hazards model, we determined significant independent predictors of long-term outcomes from a total of 111 parameters evaluated in the J-MINUET study in each of our groups, including STEMI, NSTEMI+CK, and NSTEMI-CK. Then, we calculated the risk score using the regression coefficients for the determined independent predictors for the strict prediction of long-term outcomes. Results: Prognostic factors, as well as composite cardiovascular events and all-cause death, were different between STEMI, NSTEMI+CK, and NSTEMI-CK. Risk scores could effectively and powerfully predict both composite cardiovascular events and all-cause death in each group. Conclusions: The prediction of long-term outcomes using cored parameters of baseline demographics and clinical characteristics is feasible and could prove useful in establishing therapeutic strategies in patients with STEMI, NSTEMI+CK, and NSTEMI-CK. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Myocardial Infarction)
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Brief Report
The Antitumor Effect of Heparin is not Mediated by Direct NK Cell Activation
J. Clin. Med. 2020, 9(8), 2666; https://doi.org/10.3390/jcm9082666 - 18 Aug 2020
Cited by 4 | Viewed by 1119
Abstract
Natural killer (NK) cells are innate lymphocytes responsible for the elimination of infected or transformed cells. The activation or inhibition of NK cells is determined by the balance of target cell ligand recognition by stimulatory and inhibitory receptors on their surface. Previous reports [...] Read more.
Natural killer (NK) cells are innate lymphocytes responsible for the elimination of infected or transformed cells. The activation or inhibition of NK cells is determined by the balance of target cell ligand recognition by stimulatory and inhibitory receptors on their surface. Previous reports have suggested that the glycosaminoglycan heparin is a ligand for the natural cytotoxicity receptors NKp30, NKp44 (human), and NKp46 (both human and mouse). However, the effects of heparin on NK cell homeostasis and function remain unclear. Here, we show that heparin does not enhance NK cell proliferation or killing through NK cell activation. Alternatively, in mice models, heparin promoted NK cell survival in vitro and controlled B16-F10 melanoma metastasis development in vivo. In human NK cells, heparin promisingly increased interferon (IFN)-γ production in synergy with IL-12, although the mechanism remains elusive. Our data showed that heparin is not able to increase NK cell cytotoxicity. Full article
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Article
Clinical Profiles in Renal Patients with COVID-19
J. Clin. Med. 2020, 9(8), 2665; https://doi.org/10.3390/jcm9082665 - 18 Aug 2020
Cited by 11 | Viewed by 1906
Abstract
The COVID-19 pandemic has led to frequent referrals to the emergency department on suspicion of this infection in maintenance hemodialysis (MHD) and kidney transplant (KT) patients. We aimed to describe their clinical features comparing confirmed and suspected non-confirmed COVID-19 cases during the Spanish [...] Read more.
The COVID-19 pandemic has led to frequent referrals to the emergency department on suspicion of this infection in maintenance hemodialysis (MHD) and kidney transplant (KT) patients. We aimed to describe their clinical features comparing confirmed and suspected non-confirmed COVID-19 cases during the Spanish epidemic peak. Confirmed COVID-19 ((+)COVID-19) corresponds to patient with positive RT-PCR SARS-CoV-2 assay. Non-confirmed COVID-19 ((−)COVID-19) corresponds to patients with negative RT-PCR. COVID-19 was suspected in 61 patients (40/803 KT (4.9%), 21/220 MHD (9.5%)). Prevalence of (+)COVID-19 was 3.2% in KT and 3.6% in MHD patients. Thirty-four (26 KT and 8 MHD) were (+)COVID-19 and 27 (14 KT and 13 MHD) (−)COVID-19. In comparison with (−)COVID-19 patients, (+)COVID-19 showed higher frequency of typical viral symptoms (cough, dyspnea, asthenia and myalgias), pneumonia (88.2% vs. 14.3%) and LDH and CRP while lower phosphate levels, need of hospital admission (100% vs. 63%), use of non-invasive mechanical ventilation (36% vs. 11%) and mortality (38% vs. 0%) (p < 0.001). Time from symptoms onset to admission was longer in patients who finally died than in survivors (8.5 vs. 3.8, p = 0.007). In KT and MHD patients, (+)COVID-19 shows more clinical severity than suspected non-confirmed cases. Prompt RT-PCR is mandatory to confirm COVID-19 diagnosis. Full article
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
Article
Factors Associated with Adverse Cardiovascular Events in Cancer Patients Treated with Bevacizumab
J. Clin. Med. 2020, 9(8), 2664; https://doi.org/10.3390/jcm9082664 - 18 Aug 2020
Cited by 7 | Viewed by 1292
Abstract
Background: Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody commonly used for the treatment of various cancers, is often associated with adverse cardiovascular effects such as hypertension, cardiac and cerebral ischemia, thrombosis, and bleeding events. Factors associated with increased risks of adverse [...] Read more.
Background: Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody commonly used for the treatment of various cancers, is often associated with adverse cardiovascular effects such as hypertension, cardiac and cerebral ischemia, thrombosis, and bleeding events. Factors associated with increased risks of adverse cardiovascular effects with bevacizumab have not been intensively studied. In this study, we determined factors associated with hospital admissions due to cardiovascular complications in patients who received bevacizumab for cancer treatment. Methods and Results: We retrospectively collected data for all patients treated with bevacizumab between the 1st January 2016 and the 31st December 2017 at the Hunter New England Local Health District. Patients’ characteristics and their medical history were obtained from hospital electronic medical records. Outcome data were sourced from the Institutional Cardiac and Stroke Outcomes Unit database. A total of n = 230 patients (mean age 65, males n = 124 (53.9%)) were treated with bevacizumab during the study period. N = 28 patients were admitted to hospital for a major cardiovascular-related event. Higher total treatment dose (p < 0.05), concomitant hypertension (p = 0.005), diabetes (p = 0.04), atrial fibrillation (p = 0.03), and lack of use of statin therapy (p = 0.03) were key contributors to hospital admission. Conclusions: Results of our study highlight the fact that patients with concomitant baseline cardiovascular disease/risk factors are at an increased risk of cardiovascular hospitalization related to bevacizumab treatment. Careful baseline cardiovascular assessment may be an essential step to minimize cardiovascular complications. Full article
Article
The Effects of Longitudinal White Matter Hyperintensity Change on Cognitive Decline and Cortical Thinning over Three Years
J. Clin. Med. 2020, 9(8), 2663; https://doi.org/10.3390/jcm9082663 - 17 Aug 2020
Cited by 5 | Viewed by 1190
Abstract
White matter hyperintensity (WMH) has been recognised as a surrogate marker of small vessel disease and is associated with cognitive impairment. We investigated the dynamic change in WMH in patients with severe WMH at baseline, and the effects of longitudinal change of WMH [...] Read more.
White matter hyperintensity (WMH) has been recognised as a surrogate marker of small vessel disease and is associated with cognitive impairment. We investigated the dynamic change in WMH in patients with severe WMH at baseline, and the effects of longitudinal change of WMH volume on cognitive decline and cortical thinning. Eighty-seven patients with subcortical vascular mild cognitive impairment were prospectively recruited from a single referral centre. All of the patients were followed up with annual neuropsychological tests and 3T brain magnetic resonance imaging. The WMH volume was quantified using an automated method and the cortical thickness was measured using surface-based methods. Participants were classified into WMH progression and WMH regression groups based on the delta WMH volume between the baseline and the last follow-up. To investigate the effects of longitudinal change in WMH volume on cognitive decline and cortical thinning, a linear mixed effects model was used. Seventy patients showed WMH progression and 17 showed WMH regression over a three-year period. The WMH progression group showed more rapid cortical thinning in widespread regions compared with the WMH regression group. However, the rate of cognitive decline in language, visuospatial function, memory and executive function, and general cognitive function was not different between the two groups. The results of this study indicated that WMH volume changes are dynamic and WMH progression is associated with more rapid cortical thinning. Full article
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Article
Disseminated Intravascular Coagulopathy Is Associated with the Outcome of Persistent Inflammation, Immunosuppression and Catabolism Syndrome
J. Clin. Med. 2020, 9(8), 2662; https://doi.org/10.3390/jcm9082662 - 17 Aug 2020
Cited by 3 | Viewed by 1164
Abstract
Persistent inflammation, immunosuppression and catabolism syndrome (PIICS) often occur after critical care. Disseminated intravascular coagulation (DIC) is expected to be associated independently with PIICS development. We retrospectively analyzed 5397 patients admitted to the Hitachi General Hospital emergency and critical care center during four [...] Read more.
Persistent inflammation, immunosuppression and catabolism syndrome (PIICS) often occur after critical care. Disseminated intravascular coagulation (DIC) is expected to be associated independently with PIICS development. We retrospectively analyzed 5397 patients admitted to the Hitachi General Hospital emergency and critical care center during four years. We classified PIICS as C-reactive protein > 3.0 mg/dL or albumin < 3.0 g/dL or lymphocyte count < 800/μL on day 14. Prolonged hospital stay (>14 days) without PIICS and early recovery (discharged alive within 14 days) were assigned as non-PIICS. Early death (death within 14 days) was identified. We analyzed the association between the International Society on Thrombosis and Haemostasis overt DIC and PIICS outcomes. Results revealed 488 PIICS, 416 early death and 4493 non-PIICS cases. Analyses showed DIC as associated significantly with mortality, the Barthel index at discharge and PIICS development. Multivariate regression analysis and a generalized structural equation model identified DIC on admission as an independent risk factor for PIICS in surviving patients. Full article
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Review
The Role of Dendritic Cells in TB and HIV Infection
J. Clin. Med. 2020, 9(8), 2661; https://doi.org/10.3390/jcm9082661 - 17 Aug 2020
Cited by 1 | Viewed by 1243
Abstract
Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). The [...] Read more.
Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). The altered response of dendritic cells leads to decreased activity of T-helper-1 (Th1), Th2, Regulatory T cells (Tregs), and Th17 cells in tuberculosis (TB) infections due to a diminishment of cytokine release from these APCs, while HIV infection leads to DC maturation, allowing DCs to migrate to lymph nodes and the sub-mucosa where they then transfer HIV to CD4 T cells, although there is controversy around this topic. Increases in the levels of the antioxidant glutathione (GSH) plays a critical role in maintaining dendritic cell redox homeostasis, leading to an adequate immune response with sufficient cytokine release and a subsequent robust immune response. Thus, an understanding of the intricate pathways involved in the dendritic cell response are needed to prevent co-infections and co-morbidities in individuals with TB and HIV. Full article
(This article belongs to the Special Issue Recent Advances in Mycobacterial Research)
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Article
Safety, Effect and Feasibility of Percutaneous SI-Screw with and without Augmentation—A 15-Year Retrospective Analysis on over 640 Screws
J. Clin. Med. 2020, 9(8), 2660; https://doi.org/10.3390/jcm9082660 - 17 Aug 2020
Cited by 9 | Viewed by 1177
Abstract
Background: Minimally invasive sacroiliac-screw (SI-screw) fixation of the pelvis is used in energy trauma (Arbeitsgemeinschaft für Osteosynthesefragen (AO) classified) and fragility fractures (Fragility Fracture of the Pelvis (FFP) classified). However, available clinical data are based on small case series and biomechanical data seem [...] Read more.
Background: Minimally invasive sacroiliac-screw (SI-screw) fixation of the pelvis is used in energy trauma (Arbeitsgemeinschaft für Osteosynthesefragen (AO) classified) and fragility fractures (Fragility Fracture of the Pelvis (FFP) classified). However, available clinical data are based on small case series and biomechanical data seem to be contradictory. Methods: The present single center retrospective cohort study investigated percutaneous SI-screw fixation and augmentation over 15 years. Groups were compared concerning the general epidemiological data, mobilization, complication rates, duration of stay, and safety of SI-screw insertion. Multivariable analyses were performed using logistic regression. Results: Between 2005 and March 2020, 448 patients with 642 inserted SI-screws were identified. Iatrogenic neurological impairment was documented in 2.47% and correlated with screw misplacement. There was an increased complication risk in patients with AO type C over patients with AO type B and in FFP II over FFP III/IV patients. Cement-augmented FFP patients showed a 25% reduced stay in hospital and a reduced complication risk. Cement-associated complications were seen in 22% without correlation to neurologic impairment. Conclusions: The present study confirms the safety and usability of percutaneous SI-screw fixation, despite specific risks. Cement augmentation seems to reduce the complication risk in FFP patients and shorten hospital stay for some reasons, without increased specific complications or correlated neurological impairment. Full article
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Article
Frailty and Sarcopenia Assessment upon Hospital Admission to Internal Medicine Predicts Length of Hospital Stay and Re-Admission: A Prospective Study of 980 Patients
J. Clin. Med. 2020, 9(8), 2659; https://doi.org/10.3390/jcm9082659 - 17 Aug 2020
Cited by 7 | Viewed by 943
Abstract
Background: Frailty and sarcopenia are associated with frequent hospitalizations and poor clinical outcomes in geriatric patients. Ascertaining this association for younger patients hospitalized in internal medicine departments could help better prognosticate patients in the realm of internal medicine. Methods: During a 1-year prospective [...] Read more.
Background: Frailty and sarcopenia are associated with frequent hospitalizations and poor clinical outcomes in geriatric patients. Ascertaining this association for younger patients hospitalized in internal medicine departments could help better prognosticate patients in the realm of internal medicine. Methods: During a 1-year prospective study in an internal medicine department, we evaluated patients upon admission for sarcopenia and frailty. We used the FRAIL questionnaire, blood alanine-amino transferase (ALT) activity, and mid-arm muscle circumference (MAMC) measurements. Results: We recruited 980 consecutive patients upon hospital admission (median age 72 years (IQR 65–79); 56.8% males). According to the FRAIL questionnaire, 106 (10.8%) patients were robust, 368 (37.5%) pre-frail, and 506 (51.7%) were frail. The median ALT value was 19IU/L (IQR 14–28). The median MAMC value was 27.8 (IQR 25.7–30.2). Patients with low ALT activity level (<17IU/L) were frailer according to their FRAIL score (3 (IQR 2–4) vs. 2 (IQR 1–3); p < 0.001). Higher MAMC values were associated with higher ALT activity, both representing robustness. The rate of 30 days readmission in the whole cohort was 17.4%. Frail patients, according to the FRAIL score (FS), had a higher risk for 30 days readmission (for FS > 2, HR = 1.99; 95CI = 1.29–3.08; p = 0.002). Frail patients, according to low ALT activity, also had a significantly higher risk for 30 days readmission (HR = 2.22; 95CI = 1.26–3.91; p = 0.006). After excluding patients whose length of stay (LOS) was ≥10 days, 252 (27.5%) stayed in-hospital for 4 days or longer. Frail patients according to FS had a higher risk for LOS ≥4 days (for FS > 2, HR = 1.87; 95CI = 1.39–2.52; p < 0.001). Frail patients, according to low ALT activity, were also at higher risk for LOS ≥4 days (HR = 1.87; 95CI = 1.39–2.52; p < 0.001). MAMC values were not correlated with patients’ LOS or risk for re-admission. Conclusion: Frailty and sarcopenia upon admission to internal medicine departments are associated with longer hospitalization and increased risk for re-admission. Full article
(This article belongs to the Collection Sarcopenia: Skeletal Muscle Health and Ageing)
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Article
The “No ARSA” Sign: A Novel Method of Prenatal Screening for Aberrant Right Subclavian Artery
J. Clin. Med. 2020, 9(8), 2658; https://doi.org/10.3390/jcm9082658 - 17 Aug 2020
Cited by 1 | Viewed by 1376
Abstract
An aberrant right subclavian artery (ARSA) can be overlooked by the conventional method as described by Chaoui et al., due to acoustic shadowing. The aim of this study was to evaluate the feasibility and accuracy of a novel screening method for ARSA by [...] Read more.
An aberrant right subclavian artery (ARSA) can be overlooked by the conventional method as described by Chaoui et al., due to acoustic shadowing. The aim of this study was to evaluate the feasibility and accuracy of a novel screening method for ARSA by demonstrating the brachiocephalic artery bifurcation, referred to as the “No ARSA” sign. A prospective study conducted at a tertiary care center between 2018 and 2019 included unselected pregnant patients at a median gestational age of 15.1 (14.2–22.1; IQR (inter-quartile range)) weeks, who had been referred for a routine or targeted anomaly scan. All participants were scanned for the presence or absence of ARSA using both the conventional and the novel “No ARSA” methods for validation purposes. A total of 226 unselected patients were enrolled in the study. The “No ARSA” sign was visualized in 218 fetuses (96.5%). In the remaining 8 cases (3.5%), the “No ARSA” sign was not demonstrated. In these fetuses, an ARSA was visualized by the conventional method. The new method exhibited 100% feasibility and was in complete agreement with the conventional method. Intra- and inter-observer agreement was excellent (κ = 1). The results of the study suggest that the “No ARSA” sign is an efficient and reliable screening tool for ARSA. Full article
(This article belongs to the Special Issue New Prospects for Prenatal Diagnosis and Fetal Therapy)
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Article
Comparison of Drusen Volume Assessed by Two Different OCT Devices
J. Clin. Med. 2020, 9(8), 2657; https://doi.org/10.3390/jcm9082657 - 17 Aug 2020
Cited by 2 | Viewed by 1152
Abstract
To compare drusen volume between Heidelberg Spectral Domain (SD-) and Zeiss Swept-Source (SS) PlexElite Optical Coherence Tomography (OCT) determined by manual and automated segmentation methods. Thirty-two eyes of 24 patients with Age-Related Macular Degeneration (AMD) and drusen maculopathy were included. In the central [...] Read more.
To compare drusen volume between Heidelberg Spectral Domain (SD-) and Zeiss Swept-Source (SS) PlexElite Optical Coherence Tomography (OCT) determined by manual and automated segmentation methods. Thirty-two eyes of 24 patients with Age-Related Macular Degeneration (AMD) and drusen maculopathy were included. In the central 1 and 3 mm ETDRS circle drusen volumes were calculated and compared. Drusen segmentation was performed using automated manufacturer algorithms of the two OCT devices. Then, the automated segmentation was manually corrected and compared and finally analyzed using customized software. Though on SD-OCT, there was a significant difference of mean drusen volume prior to and after manual correction (mean difference: 0.0188 ± 0.0269 mm3, p < 0.001, corr. p < 0.001, correlation of r = 0.90), there was no difference found on SS-OCT (mean difference: 0.0001 ± 0.0003 mm3, p = 0.262, corr. p = 0.524, r = 1.0). Heidelberg-acquired mean drusen volume after manual correction was significantly different from Zeiss-acquired drusen volume after manual correction (mean difference: 0.1231 ± 0.0371 mm3, p < 0.001, corr. p < 0.001, r = 0.68). Using customized software, the difference of measurements between both devices decreased and correlation among the measurements improved (mean difference: 0.0547 ± 0.0744 mm3, p = 0.02, corr. p = 0.08, r = 0.937). Heidelberg SD-OCT, the Zeiss PlexElite SS-OCT, and customized software all measured significantly different drusen volumes. Therefore, devices/algorithms may not be interchangeable. Third-party customized software helps to minimize differences, which may allow a pooling of data of different devices, e.g., in multicenter trials. Full article
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Article
Association of Regional Bone Synthetic Activities of Vertebral Corners and Vertebral Bodies Quantified Using 18F-Fluoride Positron Emission Tomography with Bone Mineral Density on Dual Energy X-ray Absorptiometry in Patients with Ankylosing Spondylitis
J. Clin. Med. 2020, 9(8), 2656; https://doi.org/10.3390/jcm9082656 - 17 Aug 2020
Cited by 1 | Viewed by 736
Abstract
We investigated whether the bone-synthetic activities of vertebral bodies or vertebral corners quantified using 18F-fluoride positron emission tomography (PET) was associated with bone mineral density (BMD) at the corresponding lumbar vertebrae in ankylosing spondylitis (AS) at each vertebra level. We analyzed 48 [...] Read more.
We investigated whether the bone-synthetic activities of vertebral bodies or vertebral corners quantified using 18F-fluoride positron emission tomography (PET) was associated with bone mineral density (BMD) at the corresponding lumbar vertebrae in ankylosing spondylitis (AS) at each vertebra level. We analyzed 48 lumbar vertebrae in 12 AS patients who underwent 18F-fluoride PET and dual energy X-ray absorptiometry (DXA). The mean standardized uptake values (SUVmean) of the vertebral body and corners from L1 to L4 were measured using the spatially separated region of interest (ROI). The L1–L4 BMDs were calculated based on the DXA (“conventional BMD”). The BMD of the internal vertebral bodies was measured by manually drawing ROIs to represent the trabecular BMD (“alternative BMD”). After adjusting the within-patient correlation, the 18F-fluoride SUVmean of the vertebral corners but not that of vertebral bodies was significantly related with the conventional BMD of the vertebra. Otherwise, the 18F-fluoride uptake of both the vertebral and vertebral bodies was significantly related with the alternative BMD. The bone-synthetic activities of the vertebral corners may be more closely related with BMD than those of the vertebral bodies, suggesting that the effects of regional bone metabolism at the vertebral corners and bodies on BMD differ in AS. Full article
(This article belongs to the Special Issue Positron Emission Tomography (PET) in a Variety of Disease Processes)
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Article
Palmitic Acid Targets Human Testicular Peritubular Cells and Causes a Pro-Inflammatory Response
J. Clin. Med. 2020, 9(8), 2655; https://doi.org/10.3390/jcm9082655 - 17 Aug 2020
Viewed by 961
Abstract
Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells [...] Read more.
Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 µM significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta (IL1beta) were not affected. The contractility marker calponin (CNN1) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys (n = 3), fed with a Western Style diet. They had elevated 2–5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated. Full article
(This article belongs to the Special Issue Updates in Male Infertility)
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Article
Pattern of Recurrence and Patient Survival after Perioperative Chemotherapy with 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) for Locally Advanced Esophagogastric Adenocarcinoma in Patients Treated Outside Clinical Trials
J. Clin. Med. 2020, 9(8), 2654; https://doi.org/10.3390/jcm9082654 - 16 Aug 2020
Cited by 8 | Viewed by 1104
Abstract
Background: The 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) protocol provides superior oncologic results compared to other perioperative chemotherapeutic protocols for the treatment of non-metastatic esophagogastric cancer (EGAC). Survival and the pattern of recurrence of EGAC after FLOT and curative tumor resection are analyzed [...] Read more.
Background: The 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) protocol provides superior oncologic results compared to other perioperative chemotherapeutic protocols for the treatment of non-metastatic esophagogastric cancer (EGAC). Survival and the pattern of recurrence of EGAC after FLOT and curative tumor resection are analyzed in a collective of patients treated outside clinical trials. Methods: Two-hundred-seventy-seven patients with EGAC (cT3-4 and/or cN+) were treated with perioperative FLOT-chemotherapy plus curative surgery between 2009 and 2018. Data were analyzed retrospectively from a prospective database. Results: Two-hundred-twenty-eight patients were included in the analysis. Postoperative in-hospital mortality was 2%. The median survival was 61–months, and median recurrence-free survival was 42 months. Multivariate analysis identified postoperative nodal status and T-stage as independent predictors of improved overall and recurrence-free survival. Administration of adjuvant chemotherapy failed to be significant for overall survival but was an independent predictor of recurrence-free survival. Recurrence occurred after a median of 9 months (range 1–46 months). Eighty-nine percent of recurrence occurred during the first 24 months. The rate of local recurrence was low. After surgery for gastric cancer, the major recurrence site was peritoneal carcinomatosis (56%), while esophageal cancer recurred mostly as metastasis to distant organs (78%). The specific site of recurrence had no impact on overall survival time. Conclusion: Real-life application of FLOT shows oncologic results comparable to clinical trials. Recurrence after FLOT and surgery for EGAC occurs predominantly early within the first two years after surgery and in the form of distant organ metastasis for esophageal tumors or peritoneal carcinomatosis for gastric tumors. Full article
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Article
Notching and Pulsatility Index of the Uterine Arteries and Preeclampsia in Twin Pregnancies
J. Clin. Med. 2020, 9(8), 2653; https://doi.org/10.3390/jcm9082653 - 15 Aug 2020
Viewed by 974
Abstract
Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20–22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the [...] Read more.
Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20–22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the combination of notching and PI of the uterine arteries to screen for preeclampsia. This was done in a cohort of 380 twin pregnancies. The results showed that the combination of notching and the highest PI above the 95th centile of the uterine arteries gives the best screening characteristics for preeclampsia in twin pregnancies. We calculated sensitivities for preeclampsia for notching, highest PI, and the combination of notching and the highest PI of 50%, 45% and 91%, with specificities of 96%, 96% and 93%, respectively. The present findings demonstrate that notching, increased highest PI, and the combination of notching and the highest PI of the uterine arteries is associated with an increased risk of preeclampsia in twin pregnancies. We observed the highest sensitivity and specificity by using the combination of notching and the highest PI of the uterine arteries. Full article
(This article belongs to the Special Issue Improving Perinatal Outcomes in Twin and Multiple Pregnancy)
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Article
Short-Term Effects of a Myofunctional Appliance on Atypical Swallowing and Lip Strength: A Prospective Study
J. Clin. Med. 2020, 9(8), 2652; https://doi.org/10.3390/jcm9082652 - 15 Aug 2020
Cited by 2 | Viewed by 2236
Abstract
Atypical swallowing needs treatment in order to eliminate harmful interferences of the tongue, which prevent the harmonious growth of the stomatognathic system. The purpose of this study was to assess the effects of a functional appliance on the presence of atypical swallowing, analyzing [...] Read more.
Atypical swallowing needs treatment in order to eliminate harmful interferences of the tongue, which prevent the harmonious growth of the stomatognathic system. The purpose of this study was to assess the effects of a functional appliance on the presence of atypical swallowing, analyzing the lip strength and the altered facial mimics. The effects of a myofunctional appliance (the Froggy Mouth) were evaluated on 40 children (6 males; 24 females; mean age 9.6 ± 2.17) with atypical swallowing—with tongue thrust diagnosed by an expert orthodontist—before and during a 6 month treatment. Data were analyzed over time with a paired samples t-test for normally distributed data. After 6 months of treatment, 33 children out of 40 achieved clinical correction of atypical swallowing due to their good compliance, even at an early stage. Seven children showed low compliance and did not obtain any result. Lip strength in compliant subjects went from 190.30 ± 86.04 cN to 489.39 ± 123.36 cN (t = p < 0.001). Facial mimics improved in 28 out of 33 compliant subjects, and four children with the initial diagnosis of labial incompetence achieved correction. This observational study demonstrates the short-term efficacy of this myofunctional appliance in the treatment of atypical swallowing, achieving correction of the facial mimics and labial incompetence with a significant improvement of the lip strength. Full article
(This article belongs to the Section Otolaryngology)
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Article
Effect of Children’s Weight Status on Physical Activity and Sedentary Behavior during Physical Education, Recess, and After School
J. Clin. Med. 2020, 9(8), 2651; https://doi.org/10.3390/jcm9082651 - 15 Aug 2020
Cited by 5 | Viewed by 1243
Abstract
Children’s body mass index may affect physical activity (PA) participation. Therefore, this study examined the effect of children’s weight status on underserved elementary school children’s PA and sedentary behavior (SB) throughout the segmented day. Participants were 138 children (X¯age = [...] Read more.
Children’s body mass index may affect physical activity (PA) participation. Therefore, this study examined the effect of children’s weight status on underserved elementary school children’s PA and sedentary behavior (SB) throughout the segmented day. Participants were 138 children (X¯age = 8.14 years). Children’s height and weight were measured with subsequent classification of children as healthy weight or overweight/obese. Durations of moderate-to-vigorous PA (MVPA), light PA (LPA), and SB during physical education (PE), morning recess, lunch recess, after school, and overall were assessed via accelerometry over three days. Independent t-tests evaluated differences in children’s MVPA, LPA, and SB during each daily segment by weight status. Significantly higher MVPA was observed for children of healthy weight status versus children with overweight/obesity during morning recess, t(136) = 2.15, p = 0.03, after school, t(136) = 2.68, p < 0.01, and overall, t(136) = 2.65, p < 0.01. Interestingly, comparisons of children of healthy weight status and children with overweight/obesity’s LPA and SB during the after-school segment revealed a trend wherein children with overweight/obesity participated in slightly greater LPA/less SB than children of healthy weight status. Higher MVPA was observed among children of healthy weight versus children with overweight/obesity during most daily segments. Concerted efforts should focus on increasing MVPA among children with overweight/obesity. Full article
(This article belongs to the Section Epidemiology & Public Health)
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