Journal of Clinical Medicine

9 pages, 511 KiB

Open AccessArticle

Prevalence and Associated Factors of Nocturnal Eating Behavior and Sleep-Related Eating Disorder-Like Behavior in Japanese Young Adults: Results of an Internet Survey Using Munich Parasomnia Screening

by Kentaro Matsui, Yoko Komada, Katsuji Nishimura, Kenichi Kuriyama and Yuichi Inoue

J. Clin. Med. 2020, 9(4), 1243; https://doi.org/10.3390/jcm9041243 - 24 Apr 2020

Cited by 18 | Viewed by 4787

Abstract

Nocturnal (night) eating syndrome and sleep-related eating disorder have common characteristics, but are considered to differ in their level of consciousness during eating behavior and recallability. To date, there have been no large population-based studies determining their similarities and differences. We conducted a [...] Read more.

Nocturnal (night) eating syndrome and sleep-related eating disorder have common characteristics, but are considered to differ in their level of consciousness during eating behavior and recallability. To date, there have been no large population-based studies determining their similarities and differences. We conducted a cross-sectional web-based survey for Japanese young adults aged 19–25 years to identify factors associated with nocturnal eating behavior and sleep-related eating disorder-like behavior using Munich Parasomnia Screening and logistic regression. Of the 3347 participants, 160 (4.8%) reported experiencing nocturnal eating behavior and 73 (2.2%) reported experiencing sleep-related eating disorder-like behavior. Smoking (p < 0.05), use of hypnotic medications (p < 0.01), and previous and/or current sleepwalking (p < 0.001) were associated with both nocturnal eating behavior and sleep-related eating disorder-like behavior. A delayed sleep-wake schedule (p < 0.05) and sleep disturbance (p < 0.01) were associated with nocturnal eating behavior but not with sleep-related eating disorder-like behavior. Both nocturnal eating behavior and sleep-related eating disorder-like behavior had features consistent with eating disorders or parasomnias. Nocturnal eating behavior but not sleep-related eating disorder-like behavior was characterized by a sleep-awake phase delay, perhaps representing an underlying pathophysiology of nocturnal eating syndrome. Full article

(This article belongs to the Special Issue Advances in Eating Disorders)

► Show Figures

Figure 1

19 pages, 2766 KiB

Open AccessFeature PaperArticle

The TAGA Study: A Study of Factors Determining Aortic Diameter in Families at High Risk of Abdominal Aortic Aneurysm Reveal Two New Candidate Genes

by Olga Peypoch, Ferran Paüls-Vergés, Miquel Vázquez-Santiago, Jaime Dilme, Jose Romero, Jordi Giner, Vicente Plaza, Jose Roman Escudero, Jose Manuel Soria, Mercedes Camacho and Maria Sabater-Lleal

J. Clin. Med. 2020, 9(4), 1242; https://doi.org/10.3390/jcm9041242 - 24 Apr 2020

Cited by 2 | Viewed by 3750

Abstract

A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A [...] Read more.

A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A Genomic Analysis (TAGA) study comprises 407 individuals related in 12 families. Each family was collected through a proband with AAA. We calculated heritability and genetic correlations between abdominal aortic diameter and clinical parameters. A genome-wide linkage scan was performed based on 4.6 million variants. A predictive model was calculated with conditional forest. Heritability of the abdominal aortic diameter was 34%. Old age, male sex, higher height, weight, creatinine levels in serum, and better lung capacity were the best predictors of aortic diameter. Linkage analyses suggested the implication of Epidermal Growth Factor Receptor (EGFR) and Betacellulin (BTC) genes with aortic diameter. This is the first study to evaluate genetic components of variation of the aortic diameter in a population of AAA high-risk individuals. These results reveal EGFR, a gene that had been previously implicated in AAA, as a determinant of aortic diameter variation in healthy genetically enriched individuals, and might indicate that a common genetic background could determine the diameter of the aorta and future risk of AAA. Full article

(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)

► Show Figures

Graphical abstract

11 pages, 1745 KiB

Open AccessArticle

Dupilumab for the Treatment of Atopic Dermatitis in an Austrian Cohort-Real-Life Data Shows Rosacea-Like Folliculitis

by Tamara Quint, Patrick M. Brunner, Christoph Sinz, Irene Steiner, Robin Ristl, Kornelia Vigl, Susanne Kimeswenger, Katharina Neubauer, Detlev Pirkhammer, Martin Zikeli, Wolfram Hoetzenecker, Norbert Reider and Christine Bangert

J. Clin. Med. 2020, 9(4), 1241; https://doi.org/10.3390/jcm9041241 - 24 Apr 2020

Cited by 29 | Viewed by 6342

Abstract

Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD). Efficacy and safety have been demonstrated in clinical trials, but real-life data is still limited. The objective of this study was to retrospectively evaluate Dupilumab treatment in AD patients in a [...] Read more.

Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD). Efficacy and safety have been demonstrated in clinical trials, but real-life data is still limited. The objective of this study was to retrospectively evaluate Dupilumab treatment in AD patients in a real-life clinical setting. Effectiveness and safety outcomes were collected at baseline and after 2, 6, 10, 24, 39, and 52 weeks by using clinical scores for disease activity, as well as serological markers. Ninety-four patients from five dermatological hospitals were included. After 24 weeks of treatment, the median Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI) showed a significant reduction compared to baseline (3.9 ± 0.7 vs. 1.4 ± 0.8 and 26.5 ± 12.5 vs. 6.4 ± 6.5). Interestingly, we observed rosacea-like folliculitis as an unexpected side effect in 6.4% of patients. Dupilumab proves to be an effective and well-tolerated treatment under real-life conditions. The occurrence of rosacea-like folliculitis warrants further mechanistic investigation. Full article

(This article belongs to the Special Issue Management of Atopic Dermatitis)

► Show Figures

Figure 1

Figure 1
(A). Percentage of patients with an Investigator Global Assessment (IGA) of 0 or 1. Numbers within bars represent number of observations. (B). Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Body Surface Area (BSA)—Mean percentage change from baseline up to 52 weeks. (C). Improvement of the variables itch, sleep and pain (visual analog scale (VAS)) from baseline up to 52 weeks. Full article ">Figure 1 Cont.
(A). Percentage of patients with an Investigator Global Assessment (IGA) of 0 or 1. Numbers within bars represent number of observations. (B). Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Body Surface Area (BSA)—Mean percentage change from baseline up to 52 weeks. (C). Improvement of the variables itch, sleep and pain (visual analog scale (VAS)) from baseline up to 52 weeks. Full article ">Figure 2
Atopic dermatitis with side effects of special interest. From left to right: Clinical picture of rosacea-like folliculitis lesions. Reflectance confocal microscopy (RCM) of Demodex mites. Mites emerge as multiple rounded structures within the hair follicles (arrows). Histopathology of a representative lesion showing typical features of folliculitis and perifolliculitis. Full article ">Figure 3
Quantification of Demodex mites and follicles in atopic dermatitis (AD) patients with (red) and without (blue) rosacea-like folliculitis. (A) There was no significant difference between the counted number of follicles in the rosacea-like folliculitis group and the control group. (B) Patients with rosacea-like folliculitis showed higher numbers of Demodex mites within an area of 100 mm2. (C) A higher number of mites per follicle was observed in patients with rosacea-like folliculitis than in controls. All results are computed as mean values including standard deviation (SD). Due to low patient numbers results are not significant but show a clear trend. Full article ">

8 pages, 2079 KiB

Open AccessArticle

A Meta-Analysis on the Effect of Dexamethasone on the Sugammadex Reversal of Rocuronium-Induced Neuromuscular Block

by Chang-Hoon Koo, Jin-Young Hwang, Seong-Won Min and Jung-Hee Ryu

J. Clin. Med. 2020, 9(4), 1240; https://doi.org/10.3390/jcm9041240 - 24 Apr 2020

Cited by 2 | Viewed by 2581

Abstract

Sugammadex reverses the rocuronium-induced neuromuscular block by trapping the cyclopentanoperhydrophenanthrene ring of rocuronium. Dexamethasone shares the same steroidal structure with rocuronium. The purpose of this study was to evaluate the influence of dexamethasone on neuromuscular reversal of sugammadex after general anesthesia. Electronic databases [...] Read more.

Sugammadex reverses the rocuronium-induced neuromuscular block by trapping the cyclopentanoperhydrophenanthrene ring of rocuronium. Dexamethasone shares the same steroidal structure with rocuronium. The purpose of this study was to evaluate the influence of dexamethasone on neuromuscular reversal of sugammadex after general anesthesia. Electronic databases were searched to identify all trials investigating the effect of dexamethasone on neuromuscular reversal of sugammadex after general anesthesia. The primary outcome was time for neuromuscular reversal, defined as the time to reach a Train-of-Four (TOF) ratio of 0.9 after sugammadex administration. The secondary outcome was the time to extubation after sugammadex administration. The mean difference (MD) and 95% CI were used for these continuous variables. Six trials were identified; a total of 329 patients were included. The analyses indicated that dexamethasone did not influence the time for neuromuscular reversal of sugammadex (MD −3.28, 95% CI −36.56 to 29.99, p = 0.847) and time to extubation (MD 25.99, 95% CI −4.32 to 56.31, p = 0.093) after general anesthesia. The results indicate that dexamethasone did not influence the neuromuscular reversal of sugammadex in patients after general anesthesia. Therefore, the dexamethasone does not appear to interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing general anesthesia for elective surgery. Full article

(This article belongs to the Section Anesthesiology)

► Show Figures

Figure 1

14 pages, 859 KiB

Open AccessReview

Therapeutic Physical Exercise Post-Treatment in Breast Cancer: A Systematic Review of Clinical Practice Guidelines

by Alicia del-Rosal-Jurado, Rita Romero-Galisteo, Manuel Trinidad-Fernández, Manuel González-Sánchez, Antonio Cuesta-Vargas and Maria Ruiz-Muñoz

J. Clin. Med. 2020, 9(4), 1239; https://doi.org/10.3390/jcm9041239 - 24 Apr 2020

Cited by 18 | Viewed by 6329

Abstract

Advances achieved in diagnosis and improvements in treatment for breast cancer have resulted in a favourable survival rate. Therapeutic physical exercise (TPE) is presented as an intervention strategy that seeks to improve the functional capabilities of the subject. To analyse if clinical practice [...] Read more.

Advances achieved in diagnosis and improvements in treatment for breast cancer have resulted in a favourable survival rate. Therapeutic physical exercise (TPE) is presented as an intervention strategy that seeks to improve the functional capabilities of the subject. To analyse if clinical practice guidelines recommend therapeutic physical exercise to reduce the adverse effects of treatment in breast cancer survivors, and on what level of scientific evidence are these recommendations based. This systematic review was prepared by searching nine electronic databases to identify eligible studies. Thirteen met the criteria for inclusion. The Appraisal of Guidelines for Research and Evaluation (AGREE II) scale was used to analyse the quality of Clinical Practice Guideline (CPGs). The percentages obtained ranged between 30.07% and 75.70%. Specifically, the highest degree of evidence could be found in the application of TPE to offset adverse effects leading to effects such as: an increase in the quality of life, fatigue reduction, and reduction in body weight alterations. TPE is presented as an optimal intervention strategy to alleviate the negative effects that patients with breast cancer suffer as a result of the treatments received. The level of evidence that supports this claim is very strong for the majority of the side effects analysed. However, this evidence is not always included in the clinical practice guidelines. Full article

(This article belongs to the Section Oncology)

► Show Figures

Figure 1

9 pages, 1768 KiB

Open AccessArticle

A New Method of Measuring the Volumetric Change of Alveolar Bone Around Dental Implants Using Computed Tomography

by Young-Wook Lim, Young-Jun Lim, Bongju Kim and Seung-Pyo Lee

J. Clin. Med. 2020, 9(4), 1238; https://doi.org/10.3390/jcm9041238 - 24 Apr 2020

Cited by 9 | Viewed by 3547

Abstract

This study proposes a method for measuring the volumetric change of alveolar bone after dental implant surgery using computed tomography (CT). A total of 40 implants in 20 patients (15 males and 5 females) were selected. The types of implants used were group [...] Read more.

This study proposes a method for measuring the volumetric change of alveolar bone after dental implant surgery using computed tomography (CT). A total of 40 implants in 20 patients (15 males and 5 females) were selected. The types of implants used were group 1: 24 CMI IS-II Active implants (Neobiotech Co., Seoul, Republic of Korea) and group 2: 16 SLActive Bone Level implants (Institut Straumann AG, Basel, Switzerland). The OnDemand3D software (CyberMed, Seoul, Korea) was used for analysis. The volumetric change of the alveolar bone around an implant fixture is measured as follows: (1) Establish two cylinders: the main cylinder with the implant axis as the central axis (radius of implant + 3 mm) and the error correction cylinder (radius of implant + 1 mm). (2) The height of the cylinder extended from the top of the fixture to a 3 mm coronal portion. (3) Calculate the volumetric change of the alveolar bone (Vd) by subtracting the volume of the error correction cylinder from the main cylinder between CT images taken immediately after the implant placement and 12 months later. After a one-year installation, the volumetric change of alveolar bone, ΔV (cc) had increased in both groups (group 1: −0.011 ± 0.015 cc, group 2: −0.012 ± 0.017 cc) with statistical significance (p < 0.05), and the difference between the groups was not statistically significant (p > 0.05). This three-dimensional assessment method would be a useful clinical reference for the assessment of marginal bone change after implant surgery. Full article

(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy 2.0)

► Show Figures

Figure 1

15 pages, 3025 KiB

Open AccessReview

Which Child with Asthma is a Candidate for Biological Therapies?

by Andrew Bush

J. Clin. Med. 2020, 9(4), 1237; https://doi.org/10.3390/jcm9041237 - 24 Apr 2020

Cited by 14 | Viewed by 4920

Abstract

In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are [...] Read more.

In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab. There is good evidence of efficacy for omalizumab, particularly in those with multiple asthma attacks, but only paediatric safety, not efficacy, data for mepolizumab. There is an urgent need for efficacy data in children, as well as data on biomarkers to guide therapy, if the right children are to be treated with these powerful new therapies. Full article

(This article belongs to the Special Issue Asthma and Allergic Inflammation: Risks, Mechanisms, and New Treatments)

► Show Figures

Figure 1

13 pages, 589 KiB

Open AccessArticle

Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage

by Michael Bender, Kristin Haferkorn, Michaela Friedrich, Eberhard Uhl and Marco Stein

J. Clin. Med. 2020, 9(4), 1236; https://doi.org/10.3390/jcm9041236 - 24 Apr 2020

Cited by 28 | Viewed by 3574

Abstract

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact [...] Read more.

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. Patients and Methods: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients’ demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. Results: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193–2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005–1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden’s Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). Conclusions: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

► Show Figures

Figure 1

10 pages, 1463 KiB

Open AccessArticle

Rethinking Radical Surgery in Interval Debulking Surgery for Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy

by Yong Jae Lee, Jung-Yun Lee, Eun Ji Nam, Sang Wun Kim, Sunghoon Kim and Young Tae Kim

J. Clin. Med. 2020, 9(4), 1235; https://doi.org/10.3390/jcm9041235 - 24 Apr 2020

Cited by 11 | Viewed by 3986

Abstract

The aim of this study is to evaluate the effects on survival outcomes of the disease burden before interval debulking surgery (IDS), surgical complexity, and residual disease after IDS in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC). We reviewed the data of [...] Read more.

The aim of this study is to evaluate the effects on survival outcomes of the disease burden before interval debulking surgery (IDS), surgical complexity, and residual disease after IDS in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC). We reviewed the data of 268 epithelial ovarian cancer patients who had received three or four cycles of NAC and undergone optimal resections through IDS. The Kaplan–Meier method and Cox regression analysis were used to assess the effects of disease burden (peritoneal cancer index (PCI)), degree of complexity of surgery (surgical complexity score/s (SCS)), and extent of residual disease. In no residual disease (R0) patients, those with intermediate/high SCS had shorter progression-free survival (PFS; p = 0.001) and overall survival (OS; p = 0.001) than patients with low SCS. An analysis of a subset of patients with R0 and low PCIs showed those with intermediate/high SCS had worse PFS and OS than patients with low SCS (p = 0.049) and OS (p = 0.037). In multivariate analysis, patients with R0 as a result of intermediate/high SCS fared worse than patients whose R0 was achieved by low SCS (PFS hazard ratio (HR) 1.80, 95% CI 1.05–3.10; OS HR 5.59, 95% CI 1.70–18.39). High PCIs at the time of IDS, high SCS, and residual disease signal poor prognoses for patients treated with NAC. Full article

(This article belongs to the Special Issue Epithelial Ovarian Cancer: Focus on Targeted and Complementary Therapy)

► Show Figures

Figure 1

11 pages, 1096 KiB

Open AccessArticle

Incident Comorbidities, Aging and the Risk of Stroke in 608,108 Patients with Atrial Fibrillation: A Nationwide Analysis

by Laurent Fauchier, Alexandre Bodin, Arnaud Bisson, Julien Herbert, Pascal Spiesser, Nicolas Clementy, Dominique Babuty, Tze-Fan Chao and Gregory Y. H. Lip

J. Clin. Med. 2020, 9(4), 1234; https://doi.org/10.3390/jcm9041234 - 24 Apr 2020

Cited by 29 | Viewed by 3215

Abstract

Background: We hypothesized that the change in stroke risk profile between baseline and follow-up may be a better predictor of ischemic stroke than the baseline stroke risk determination using the CHA₂DS₂-VASc score ((congestive heart failure, hypertension, age ≥75 years [...] Read more.

Background: We hypothesized that the change in stroke risk profile between baseline and follow-up may be a better predictor of ischemic stroke than the baseline stroke risk determination using the CHA₂DS₂-VASc score ((congestive heart failure, hypertension, age ≥75 years (doubled), diabetes, stroke/transient ischemic attack/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65–75 years, sex category (female))). Methods: We collected information for all patients treated with atrial fibrillation (AF) in French hospitals between 2010 and 2019. We studied 608,108 patients with AF who did not have risk factors of the CHA₂DS₂-VASc score (except for age and sex). The predictive accuracies of baseline and follow-up CHA₂DS₂-VASc scores, as well as the ‘Delta CHA₂DS₂-VASc’ (i.e., change/difference between the baseline and follow-up CHA₂DS₂-VASc scores) for prediction of ischemic stroke were studied. Results: The mean CHA₂DS₂-VASc score at baseline was 1.7, and increased to 2.4 during follow-up of 2.2 ± 2.4 years, (median (interquartile range: IQR) 1.2 (0.1–3.8) years), resulting in a mean Delta CHA₂DS₂-VASc score of 0.7. Among 20,082 patients suffering ischemic stroke during follow-up, 67.1% had a Delta CHA₂DS₂-VASc score ≥1 while they were only 40.4% in patients without ischemic stroke. The follow-up CHA₂DS₂-VASc score and Delta CHA₂DS₂-VASc score were predictors of ischemic stroke (C-index 0.670, 95% confidence interval (CI) 0.666–0.673 and 0.637, 95%CI 0.633–0.640) and they performed better than baseline CHA₂DS₂-VASc score (C-index 0.612, 95%CI 0.608–0.615, p < 0.0001). Conclusions: Stroke risk was non-static, and many AF patients had ≥1 new stroke risk factor(s) before ischemic stroke occurred. The follow-up CHA₂DS₂-VASc score and its change (i.e., ‘Delta CHA₂DS₂-VASc’) were better predictors of ischemic stroke than relying on the baseline CHA₂DS₂-VASc score. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

10 pages, 657 KiB

Open AccessArticle

The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial

by Cristina Hernández, Massimo Porta, Francesco Bandello, Jakob Grauslund, Simon P. Harding, Stephen J. Aldington, Catherine Egan, Ulrik Frydkjaer-Olsen, José García-Arumí, Jonathan Gibson, Gabriele E. Lang, Rosangela Lattanzio, Pascale Massin, Edoardo Midena, Berta Ponsati, Luísa Ribeiro, Peter Scanlon, José Cunha-Vaz and Rafael Simó

J. Clin. Med. 2020, 9(4), 1233; https://doi.org/10.3390/jcm9041233 - 24 Apr 2020

Cited by 14 | Viewed by 3531

Abstract

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric [...] Read more.

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain–optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR). Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

► Show Figures

Figure 1

12 pages, 412 KiB

Open AccessArticle

Effects of Sugammadex on Post-Operative Pulmonary Complications in Laparoscopic Gastrectomy: A Retrospective Cohort Study

by Jiwon Han, Jung-Hee Ryu, Bon-Wook Koo, Sun Woo Nam, Sang-Il Cho and Ah-Young Oh

J. Clin. Med. 2020, 9(4), 1232; https://doi.org/10.3390/jcm9041232 - 24 Apr 2020

Cited by 12 | Viewed by 3546

Abstract

The use of sugammadex can reduce post-operative residual neuromuscular blockade, which is known to increase the risk of post-operative respiratory events. However, its effect on post-operative pulmonary complications is not obvious. This study was performed to evaluate the effects of sugammadex on post-operative [...] Read more.

The use of sugammadex can reduce post-operative residual neuromuscular blockade, which is known to increase the risk of post-operative respiratory events. However, its effect on post-operative pulmonary complications is not obvious. This study was performed to evaluate the effects of sugammadex on post-operative pulmonary complications in patients undergoing laparoscopic gastrectomy between 2013 and 2017. We performed propensity score matching to correct for selection bias. Post-operative pulmonary complications (i.e., pneumonia, respiratory failure, pleural effusion, atelectasis, pneumothorax, and aspiration pneumonitis) were evaluated from the radiological and laboratory findings. We also evaluated admission to the intensive care unit after surgery, re-admission or an emergency room visit within 30 days after discharge, length of hospital stay, re-operation, and mortality within 90 days post-operatively as secondary outcomes. In the initial cohort of 3802 patients, 541 patients were excluded, and 1232 patients were analyzed after propensity score matching. In the matched cohort, pleural effusion was significantly reduced in the sugammadex group compared to the neostigmine group (neostigmine 23.4% vs. sugammadex 18%, p = 0.02). Other pulmonary complications and secondary outcomes were not significantly different between the groups. In comparison to neostigmine, the use of sugammadex was associated with a lower incidence of post-operative pleural effusion in laparoscopic gastrectomy. Full article

(This article belongs to the Special Issue Postoperative Pulmonary Complications and Care)

► Show Figures

Figure 1

11 pages, 1553 KiB

Open AccessArticle

Changes in Iris Perfusion Following Scleral Buckle Surgery for Rhegmatogenous Retinal Detachment: An Anterior Segment Optical Coherence Tomography Angiography (AS-OCTA) Study

by Rossella D’Aloisio, Pasquale Viggiano, Enrico Borrelli, Mariacristina Parravano, Aharrh-Gnama Agbèanda, Federica Evangelista, Giada Ferro, Lisa Toto and Rodolfo Mastropasqua

J. Clin. Med. 2020, 9(4), 1231; https://doi.org/10.3390/jcm9041231 - 24 Apr 2020

Cited by 18 | Viewed by 3797

Abstract

Purpose: To investigate iris vasculature changes following scleral buckling (SB) surgery in eyes with rhegmatogenous retinal detachment (RRD) with anterior-segment (AS) optical coherence tomography angiography (OCTA). Methods: In this prospective study, enrolled subjects were imaged with an SS-OCTA system (PLEX Elite 9000, Carl [...] Read more.

Purpose: To investigate iris vasculature changes following scleral buckling (SB) surgery in eyes with rhegmatogenous retinal detachment (RRD) with anterior-segment (AS) optical coherence tomography angiography (OCTA). Methods: In this prospective study, enrolled subjects were imaged with an SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). Image acquisition of the iris was obtained using an AS lens and a manual focusing adjustment in the iris using the retina imaging software. The quantitative analysis was performed in eight different iris regions: (i) superior, (ii) supero-temporal, (iii) supero-nasal, (iv) nasal, (v) temporal, (vi) inferior, (vii) infero-temporal, (viii) infero nasal which, were defined as squares with area of 1.5 mm². Results: Fifteen eyes of 15 patients (six females; nine males) were included. Anterior segment optical coherence tomography angiography (AS-OCTA) parameters of the iris were statistically compared at baseline (preoperatively), 1 week, 1 month and 6 months after SB. At post-operative 1 week, perfusion density (PD) showed a significant decrease from 66.8 ± 13.2% to 58.55 ± 12.0% in the iris supero-nasal region (p = 0.016). However, at the 1-month follow-up visit, iris PD was significantly lower in all the analyzed iris regions, apart from the superior one. Conclusions: This study is the first description of AS-OCTA in patients undergoing SB. Our results showed a uniform reduction of the iris vessel network at 1 month after surgery, supporting the clinical use of AS-OCTA to identify early iris perfusion changes as potential predictive biomarkers of vascular disorders. Full article

(This article belongs to the Special Issue New Advances in Retinal Research)

► Show Figures

Figure 1

15 pages, 1154 KiB

Open AccessArticle

Post-Traumatic Sepsis Is Associated with Increased C5a and Decreased TAFI Levels

by Jan Tilmann Vollrath, Ingo Marzi, Anna Herminghaus, Thomas Lustenberger and Borna Relja

J. Clin. Med. 2020, 9(4), 1230; https://doi.org/10.3390/jcm9041230 - 24 Apr 2020

Cited by 16 | Viewed by 3269

Abstract

Background: Sepsis frequently occurs after major trauma and is closely associated with dysregulations in the inflammatory/complement and coagulation system. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a dual role as an anti-fibrinolytic and anti-inflammatory factor by downregulating complement anaphylatoxin C5a. The purpose of this study [...] Read more.

Background: Sepsis frequently occurs after major trauma and is closely associated with dysregulations in the inflammatory/complement and coagulation system. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a dual role as an anti-fibrinolytic and anti-inflammatory factor by downregulating complement anaphylatoxin C5a. The purpose of this study was to investigate the association between TAFI and C5a levels and the development of post-traumatic sepsis. Furthermore, the predictive potential of both TAFI and C5a to indicate sepsis occurrence in polytraumatized patients was assessed. Methods: Upon admission to the emergency department (ED) and daily for the subsequent ten days, circulating levels of TAFI and C5a were determined in 48 severely injured trauma patients (injury severity score (ISS) ≥ 16). Frequency matching according to the ISS in septic vs. non-septic patients was performed. Trauma and physiologic characteristics, as well as outcomes, were assessed. Statistical correlation analyses and cut-off values for predicting sepsis were calculated. Results: Fourteen patients developed sepsis, while 34 patients did not show any signs of sepsis (no sepsis). Overall injury severity, as well as demographic parameters, were comparable between both groups (ISS: 25.78 ± 2.36 no sepsis vs. 23.46 ± 2.79 sepsis). Septic patients had significantly increased C5a levels (21.62 ± 3.14 vs. 13.40 ± 1.29 ng/mL; p < 0.05) and reduced TAFI levels upon admission to the ED (40,951 ± 5637 vs. 61,865 ± 4370 ng/mL; p < 0.05) compared to the no sepsis group. Negative correlations between TAFI and C5a (p = 0.0104) and TAFI and lactate (p = 0.0423) and positive correlations between C5a and lactate (p = 0.0173), as well as C5a and the respiratory rate (p = 0.0266), were found. In addition, correlation analyses of both TAFI and C5a with the sequential (sepsis-related) organ failure assessment (SOFA) score have confirmed their potential as early sepsis biomarkers. Cut-off values for predicting sepsis were 54,857 ng/mL for TAFI with an area under the curve (AUC) of 0.7550 (p = 0.032) and 17 ng/mL for C5a with an AUC of 0.7286 (p = 0.034). Conclusion: The development of sepsis is associated with early decreased TAFI and increased C5a levels after major trauma. Both elevated C5a and decreased TAFI may serve as promising predictive factors for the development of sepsis after polytrauma. Full article

(This article belongs to the Special Issue New Diagnostic and Therapeutic Approaches for the Care of the Severely Injured Patient)

► Show Figures

Figure 1

Figure 1
Upon admission of severely injured trauma patients (n = 48) to the emergency department, lactate levels (A), pH values (B), heart rate (C), and respiratory rate (D) were measured. Patients were stratified to those who developed sepsis in their clinical course (sepsis, n = 14) vs. those who did not develop infectious complications (no sepsis, n = 34). Data are shown as mean ± SEM. * p < 0.05 sepsis vs. no sepsis. Full article ">Figure 2
Upon admission of severely injured trauma patients (n = 48) to the emergency department, plasma thrombin-activatable fibrinolysis inhibitor (TAFI) levels (A), plasma C5a levels (B), and leukocyte counts (C) were determined. Patients were stratified to those who developed sepsis in their clinical course (sepsis, n = 14) vs. those who did not develop infectious complications (no sepsis, n = 34). Data are shown as mean ± SEM. * p < 0.05 sepsis vs. no sepsis. Full article ">Figure 3
Correlation analysis between TAFI and C5a (A), TAFI and lactate (B), C5a and respiratory rate (C), and C5a and lactate (D) are shown. r: Pearson coefficient. Full article ">Figure 4
Receiver operating curve analyses on TAFI (A), C5a (B), leukocyte counts (C), lactate levels (D), heart rate (E), and respiratory rate (F) at admission to the emergency department to predict the development of sepsis after polytrauma are demonstrated. p < 0.05: statistically significant, AUC: area under the curve, and CI: confidence interval. Full article ">Figure 5
Upon admission of severely injured trauma patients (n = 48) to the emergency department (ED), plasma TAFI levels (A) and plasma C5a levels (B) were determined daily for ten days (D1–D10). Patients were stratified to those who developed sepsis in their clinical course (sepsis, n = 14) vs. those who did not develop infectious complications (no sepsis, n = 34). Data are shown as mean ± SEM. * p < 0.05 sepsis vs. no sepsis at the indicated time. Full article ">

14 pages, 1142 KiB

Open AccessArticle

Influence of Anesthesia and Clinical Variables on the Firing Rate, Coefficient of Variation and Multi-Unit Activity of the Subthalamic Nucleus in Patients with Parkinson’s Disease

by Michael J. Bos, Ana Maria Alzate Sanchez, Raffaella Bancone, Yasin Temel, Bianca T.A. de Greef, Anthony R. Absalom, Erik D. Gommer, Vivianne H.J.M. van Kranen-Mastenbroek, Wolfgang F. Buhre, Mark J. Roberts and Marcus L.F. Janssen

J. Clin. Med. 2020, 9(4), 1229; https://doi.org/10.3390/jcm9041229 - 24 Apr 2020

Cited by 14 | Viewed by 4010

Abstract

Background: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and [...] Read more.

Background: Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. Methods: Data from 78 patients with Parkinson’s disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. Results: We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. Conclusion: Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER. Full article

(This article belongs to the Special Issue Trends in Clinical Deep Brain Stimulation)

► Show Figures

Figure 1

Figure 1
Overview of the sorting process. (A) Example recording trajectory of one electrode with 5 s of data shown at each site. Grey shading indicates sites identified as within the subthalamic nucleus (STN). (B) Expanded view of data from one recording site (region highlighted by a dashed box in A) with the spike detection threshold set by A.M.A.S. (blue) and M.J.B. (purple); (C) clusters of the spike waveforms identified from the example recording by A.M.A.S. and M.J.B.; (D) spike waveform (mean: thick lines, thin lines: standard deviation) of the spike sorted from the example recording by A.M.A.S. and M.J.B.; (E) Autocorrelation of the spike times from the example recording by A.M.A.S. and M.J.B.; (F) The proportion of sites with identified single units (SU)s (discovery rate) was quite similar, indicating that all sorters applied comparable criteria. (G) Nevertheless, the mean firing rate of STN neurons differed somewhat between sorters. Full article ">Figure 2
Bar plot and t-test for within awake group analysis for firing rate, defined in spikes per seconds, coefficient of variation and multi-unit activity, defined as activity above 300HZ. Mean and standard error are shown in each bar. *** p < 0.001. PSA: procedural sedation and analgesia. Full article ">Figure 3
Bar plot (error bars show standard error) and t-test for the No PSA group against each PSA group for firing rate, coefficient of variation and multi-unit activity. * p < 0.05, ** p < 0.01, *** p < 0.001. CLONI: clonidine; DEX: dexmedetomidine; REMI: remifentanil; PSA: procedural sedation and analgesia. Full article ">Figure 4
Correlation analysis on the dose of DEX for the electrophysiological measures. Correlations were significant. Data of the no PSA drug group is shown in black for comparison but was excluded from the regression analysis. DEX: dexmedetomidine. Full article ">

16 pages, 1464 KiB

Open AccessArticle

The Association between Serum Levels of 25[OH]D, Body Weight Changes and Body Composition Indices in Patients with Heart Failure

by Apolonia Stefaniak, Robert Partyka, Sylwia Duda, Weronika Ostręga, Jacek Niedziela, Jolanta Nowak, Jolanta Malinowska-Borowska, Tomasz Rywik, Przemysław Leszek, Bartosz Hudzik, Barbara Zubelewicz-Szkodzińska and Piotr Rozentryt

J. Clin. Med. 2020, 9(4), 1228; https://doi.org/10.3390/jcm9041228 - 24 Apr 2020

Cited by 2 | Viewed by 2725

Abstract

We try to determine the association between weight changes (WC), both loss or gain, body composition indices (BCI) and serum levels of 25[OH]D during heart failure (HF). WC was determined in 412 patients (14.3% female, aged: 53.6 ± 10.0 years, NYHA class: 2.5 [...] Read more.

We try to determine the association between weight changes (WC), both loss or gain, body composition indices (BCI) and serum levels of 25[OH]D during heart failure (HF). WC was determined in 412 patients (14.3% female, aged: 53.6 ± 10.0 years, NYHA class: 2.5 ± 0.8). Body fat, fat percentage and fat-free mass determined by dual energy X-rays absorptiometry (DEXA) and serum levels of 25[OH]D were analyzed. Logistic regression was used to calculate odds ratios for 25[OH]D insufficiency (<30 ng/mL) or deficiency (<20 ng/mL) by quintiles of WC, in comparison to weight-stable subgroup. The serum 25[OH]D was lower in weight loosing than weight stable subgroup. In fully adjusted models the risk of either insufficient or deficient 25[OH]D levels was independent of BCI and HF severity markers. The risk was elevated in higher weight loss subgroups but also in weight gain subgroup. In full adjustment, the odds for 25[OH]D deficiency in the top weight loss and weight gain subgroups were 3.30; 95%CI: 1.37–7.93, p = 0.008 and 2.41; 95%CI: 0.91–6.38, p = 0.08, respectively. The risk of 25[OH]D deficiency/insufficiency was also independently associated with potential UVB exposure, but not with nutritional status and BCI. Metabolic instability in HF was reflected by edema-free WC, but not nutritional status. BCI is independently associated with deficiency/insufficiency of serum 25[OH]D. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

16 pages, 323 KiB

Open AccessArticle

Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study

by Maria Antonietta Barbieri, Giuseppe Cicala, Paola Maria Cutroneo, Elisabetta Gerratana, Caterina Palleria, Caterina De Sarro, Ada Vero, Luigi Iannone, Antonia Manti, Emilio Russo, Giovambattista De Sarro, Fabiola Atzeni and Edoardo Spina

J. Clin. Med. 2020, 9(4), 1227; https://doi.org/10.3390/jcm9041227 - 24 Apr 2020

Cited by 16 | Viewed by 4331

Abstract

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from [...] Read more.

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns. Full article

(This article belongs to the Section Pharmacology)

25 pages, 1974 KiB

Open AccessReview

Detection of Platelet-Activating Antibodies Associated with Heparin-Induced Thrombocytopenia

by Brigitte Tardy, Thomas Lecompte, François Mullier, Caroline Vayne and Claire Pouplard

J. Clin. Med. 2020, 9(4), 1226; https://doi.org/10.3390/jcm9041226 - 24 Apr 2020

Cited by 39 | Viewed by 12532

Abstract

Heparin-induced thrombocytopenia (HIT) is a prothrombotic immune drug reaction caused by platelet-activating antibodies that in most instances recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays (i.e., functional assays) are more specific than immunoassays, since they are able to discern clinically relevant heparin-induced [...] Read more.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic immune drug reaction caused by platelet-activating antibodies that in most instances recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays (i.e., functional assays) are more specific than immunoassays, since they are able to discern clinically relevant heparin-induced antibodies. All functional assays used for HIT diagnosis share the same principle, as they assess the ability of serum/plasma from suspected HIT patients to activate fresh platelets from healthy donors in the presence of several concentrations of heparin. Depending on the assay, donors’ platelets are stimulated either in whole blood (WB), platelet-rich plasma (PRP), or in a buffer medium (washed platelets, WP). In addition, the activation endpoint studied varies from one assay to another: platelet aggregation, membrane expression of markers of platelet activation, release of platelet granules. Tests with WP are more sensitive and serotonin release assay (SRA) is considered to be the current gold standard, but functional assays suffer from certain limitations regarding their sensitivity, specificity, complexity, and/or accessibility. However, the strict adherence to adequate preanalytical conditions, the use of selected platelet donors and the inclusion of positive and negative controls in each run are key points that ensure their performances. Full article

(This article belongs to the Special Issue Platelet Counting, Morphology Assessment and Functional Studies: Pitfalls, Uncertainties, Good Practice for Clinical Usefulness)

► Show Figures

Figure 1

Figure 1
Platelet responses induced by heparin-induced thrombocytopenia (HIT) antibodies and functional assay targets. Depending on the assay, donors’ platelets are stimulated either in whole blood (WB), platelet-rich plasma (PRP), or after washings (washed platelets, WP). Today, serotonin release assay (SRA), which measures the release of serotonin from dense granules when platelets are activated, and heparin-induced platelet aggregation (HIPA), which is based on a visual inspection of platelet aggregates, are considered the “gold standard” to confirm HIT. The oldest but probably the most used assay is light transmission aggregometry (LTA), classically performed with PRP, but which can also be carried out with WP. Platelet aggregation can also be assessed in whole blood using heparin-induced multiple electrode aggregometry (HIMEA), which considers the possible contribution of monocytes, neutrophils, and red blood cells (RBC) to platelet activation induced by HIT antibodies. Dense granules secretion may also be evaluated by measuring the ATP released using chemiluminescence. Several assays based on flow cytometry (FC) have also been proposed, most of them assessing P-selectin (CD62P) expression or Annexin V binding to phosphatidylserine on the surface of activated platelets. Full article ">Figure 2
Typical tracings obtained with light transmission aggregometry in the absence and in the presence of low (0.5 and 1 IU/mL) and high (10 IU/mL) unfractionated heparin UFH concentrations. Aggregation curves for two patients with HIT (P1 and P2) are presented here. Different lag times related to heparin concentrations and patient samples are presented. P1 antibodies appear to be more reactive than P2 antibodies. Full article ">Figure 3
Detection of heparin-dependent platelet-activating antibodies with FCA. (A) Schematic procedure of the FCA. (B) The first gate delineates the platelets ((log SSC + log FL2-PE (CD41+ events)) and the second gate is applied to analyze the activated platelets (log FL1-FITC). Determination of the activation threshold: upper panel, TRAP-activated platelets (Ctl+); lower panel, resting platelets (Ctl−), the cursor indicating the activation threshold is placed at the intersection of the FL1 histograms of the positive control (Ctl+) and the negative control (Ctl−). “%R” represents the percentage of CD-62P positive events as an index of platelet activation. This set-up allows determining percentage of the activated platelets (to the right of the activation threshold) under different conditions. (C) Incubations with patients’ plasma and one platelet donor: typical results with low (0.3 IU/mL heparin) and high (100 IU/mL heparin) concentrations of heparin (top and bottom rows, respectively). Left panels: platelets activated with a highly HIT-positive plasma (optical density, OD = 2.5); middle panels: platelets activated with a weakly HIT-positive plasma (OD = 1.3); right panels: platelets incubated with a non-HIT plasma. The HEPLA index is calculated as follows: HEPLA index = (% H 0.3 − % H 100)/(% TRAP Ctl+ − % PBS Ctl−) × 100. FCA: flow cytometric assay, SSC: sideways scatter, PE: phycoerythrin, FITC: fluorescein isothiocyanate, TRAP: thrombin receptor agonist peptide, UFH: unfractionated heparin. Full article ">Figure 4
Typical tracing obtained by whole blood impedance aggregometry. Presence of HIT antibodies activating platelets: typical tracings obtained by whole blood impedance aggregometry (Multiplate®) in the absence and in the presence of low (1 IU/mL) and high (200 IU/mL) concentrations of UFH. The whole blood aggregation is recorded for 15 min. AUC: area under curve. Full article ">

29 pages, 2387 KiB

Open AccessReview

The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control

by Yosra A. Helmy, Mohamed Fawzy, Ahmed Elaswad, Ahmed Sobieh, Scott P. Kenney and Awad A. Shehata

J. Clin. Med. 2020, 9(4), 1225; https://doi.org/10.3390/jcm9041225 - 24 Apr 2020

Cited by 468 | Viewed by 51654

Abstract

A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing [...] Read more.

A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing the disease named coronavirus disease-2019 (COVID-19). The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis. Human-to-human transmission has been confirmed even from asymptomatic carriers. The virus has spread to at least 200 countries, and more than 1,700,000 confirmed cases and 111,600 deaths have been recorded, with massive global increases in the number of cases daily. Therefore, the WHO has declared COVID-19 a pandemic. The disease is characterized by fever, dry cough, and chest pain with pneumonia in severe cases. In the beginning, the world public health authorities tried to eradicate the disease in China through quarantine but are now transitioning to prevention strategies worldwide to delay its spread. To date, there are no available vaccines or specific therapeutic drugs to treat the virus. There are many knowledge gaps about the newly emerged SARS-CoV-2, leading to misinformation. Therefore, in this review, we provide recent information about the COVID-19 pandemic. This review also provides insights for the control of pathogenic infections in humans such as SARS-CoV-2 infection and future spillovers. Full article

(This article belongs to the Special Issue Real Time Clinical and Epidemiological Investigations on Novel Coronavirus - Part I)

► Show Figures

Figure 1

Figure 1
Genome organization of SARS CoV-2 and its encoded proteins. The orf1ab gene constitutes two-thirds of the genome, encodes a total of 16 non-structural proteins (NSPs) within the pp1ab gene, as shown in yellow, which are nsp1 (180 aa), nsp2 (638 aa), nsp3 (1945 aa), nsp4 (500 aa), nsp5 (306 aa), nsp6 (290 aa), nsp7 (83 aa), nsp8 (198 aa), nsp9 (113 aa), nsp10 (139 aa), nsp11 (13 aa), nsp12 (932 aa), nsp13 (601 aa), nsp14 (527 aa), nsp15 (346 aa), and nsp16 (298 aa). The other third of SARS CoV-2 includes four genes (in green) that encode four structural proteins (S, M, E, N), and six accessory genes (in blue) that encode six accessory proteins (orf3a, orf6, orf7a, orf7b, orf8, and orf10). Full article ">Figure 2
Phylogenetic tree based on the complete genome sequences of 45 selected coronaviruses from 18 countries including the SARS-CoV-2, SARS-CoV, HCoV, bat SARS, SARS-like CoV, and MERS-CoV. The tree was constructed in IQ-TREE using the maximum likelihood method, ModelFinder, and ultrafast bootstrap approximation (1000 replicates). The tree is drawn to scale, with branch lengths (numbers below the branches) measured in the number of substitutions per site. Branch lengths less than 0.3 are not shown. Numbers above the branches represent the percentage of replicate trees in which the associated viruses clustered together in the bootstrap test. The tree is rooted with two human coronavirus species from the genus Alphacoronavirus as an outgroup (HCoV-229E and HCoV-NL63). Full article ">Figure 3
The transmission cycle of coronaviruses including MERS-CoV, SARS-CoV, and SARSCoV-2. The transmission of the virus to humans occurs by direct contact with infected animals. The continuous line represents direct transmission. Full article ">Figure 4
Lung of a 51-year-old male patient with a history of hepatitis C and symptoms of dry cough and shortness of breathing for three weeks. No recent travel or known contacts with infected subjects. Axial (A) and coronal computed tomography (CT) (B) of chest without contrast revealed bilateral peribronchial and subpleural consolidative opacities noted throughout both lungs (green arrow). There were scattered nodular consolidative opacities in a peribronchial distribution (orange arrow). The patient tested positive for SARS-CoV-2 RNA. Full article ">

4 pages, 437 KiB

Open AccessCorrection

Correction: Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in “Real Life”. J. Clin. Med. 2019, 8, 1066

by Domenico Russo, Rocco Tripepi, Fabio Malberti, Biagio Di Iorio, Bernadette Scognamiglio, Luca Di Lullo, Immacolata Gaia Paduano, Giovanni Luigi Tripepi and Vincenzo Antonio Panuccio

J. Clin. Med. 2020, 9(4), 1224; https://doi.org/10.3390/jcm9041224 - 24 Apr 2020

Cited by 1 | Viewed by 2407

Abstract

The authors wish to make the following corrections to the previous publication [...] Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

► Show Figures

Figure 1

4 pages, 175 KiB

Open AccessEditorial

Oxidative Stress in Neurodegenerative Diseases: From Preclinical Studies to Clinical Applications

by Andrea Tarozzi

J. Clin. Med. 2020, 9(4), 1223; https://doi.org/10.3390/jcm9041223 - 24 Apr 2020

Cited by 13 | Viewed by 3353

Abstract

Oxidative stress plays an important role in the pathogenesis of several different neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) [...] Full article

(This article belongs to the Special Issue Oxidative Stress in Neurodegenerative Diseases: From Preclinical Studies to Clinical Applications)

14 pages, 496 KiB

Open AccessArticle

Evaluation of the French National Program on Home Return of Patients with Chronic Heart Failure (PRADO-IC): Pilot Study of 91 Patients During Its Deployment in the Bas Rhin Area

by Mylène Radreau, Noel Lorenzo-Villalba, Samy Talha, Jean-Jacques Von Hunolstein, Michel Hanssen, Anne Koenig, Philippe Couppie, Bernard Geny, Francois Severac, Gérald Roul, Abrar-Ahmad Zulfiqar and Emmanuel Andrès

J. Clin. Med. 2020, 9(4), 1222; https://doi.org/10.3390/jcm9041222 - 23 Apr 2020

Cited by 2 | Viewed by 2987

Abstract

Objective: The main objective of this study was to evaluate the impact of the French national program on home return of chronic heart failure patients (PRADO-IC) in terms of re-hospitalizations for heart failure (HF) during its deployment in the Bas-Rhin (France). Patients and [...] Read more.

Objective: The main objective of this study was to evaluate the impact of the French national program on home return of chronic heart failure patients (PRADO-IC) in terms of re-hospitalizations for heart failure (HF) during its deployment in the Bas-Rhin (France). Patients and methods: This was a pilot, descriptive, quantitative, retrospective, and bi-centric study (University Hospitals of Strasbourg and Haguenau Hospital Center, France). It included all patients included in the PRADO-IC program from these centers between January 1, 2015 and December 31, 2015. The primary endpoint of our study was the evaluation of the number of 1-year, 6-month, and 30-day re-admissions to the hospital in relation to an acute HF episode, before and after the inclusion of patients in the PRADO-IC program. The secondary endpoints were the number of overall re-hospitalizations (all-cause); the number of days of hospitalization for HF; the time to first re-hospitalization and the average length of hospital stay, before and after inclusion in PRADO-IC; and the overall and cardiovascular mortality rates. Results: 91 patients out of 271 (33,6%) with a mean age of 79.2 years (67–94) were included. They all had chronic HF, essentially class II-III NYHA (90.1%), mostly of ischemic origin (41.9%), with altered left ventricular ejection fraction in 71.4% of cases. A reduction in the mean number of hospitalizations for HF per patient at 30 days, 6 months and 1 year was observed, respectively, from 0.18 ± 0.42 per patient before inclusion to 0.15 ± 0.36 after inclusion (p = 0.56); 0.98 ± 1.04 hospitalizations to 0.53 ± 0.81 at 6 months (p < 0.01); and 1.64 ± 1.14 hospitalizations 1.04 ± 1.05 at 1 year (p < 0.001). Patients were hospitalized less overall after inclusion in the PRADO-IC program. The number of days of hospitalization for HF was reduced after inclusion of patients from 18.02 ± 7.78 days before inclusion to 14.28 ± 11.57 days for the 6 month follow-up (p = 0.006), and from 22.07 ± 10.33 days before inclusion to 16.39 ± 15.94 days for the 1 year follow-up (p < 0.001). In contrast, inclusion in PRADO-IC statistically increased the mean time to first re-hospitalization for HF from mean 99.36 ± 72.39 days before inclusion to 148.11 ± 112.77 days after inclusion (p < 0.001). Conclusion: This study seems to demonstrate that the PRADO-IC program could improve the management of chronic HF patients in ambulatory care, particularly regarding HF re-hospitalization. However, due to the limitations of the methodology used and the small number of patients, it is advisable to consolidate its initial results with a randomized controlled study on a larger number of patients. In our opinion, its results need to be communicated because, to our knowledge, no equivalent study exists. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

16 pages, 3765 KiB

Open AccessArticle

Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

by Jacek M. Kwiecien, Liqiang Zhang, Jordan R. Yaron, Lauren N. Schutz, Christian J. Kwiecien-Delaney, Enkidia A. Awo, Michelle Burgin, Wojciech Dabrowski and Alexandra R. Lucas

J. Clin. Med. 2020, 9(4), 1221; https://doi.org/10.3390/jcm9041221 - 23 Apr 2020

Cited by 27 | Viewed by 4473

Abstract

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury [...] Read more.

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

► Show Figures

Figure 1

11 pages, 1059 KiB

Open AccessArticle

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

by Wen-Chin Lee, Lung-Chih Li, Hwee-Yeong Ng, Pei-Ting Lin, Terry Ting-Yu Chiou, Wei-Hung Kuo and Chien-Te Lee

J. Clin. Med. 2020, 9(4), 1220; https://doi.org/10.3390/jcm9041220 - 23 Apr 2020

Cited by 25 | Viewed by 4321

Abstract

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental [...] Read more.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13–15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7–9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis. Full article

(This article belongs to the Section Nephrology & Urology)

► Show Figures

Figure 1

16 pages, 2113 KiB

Open AccessReview

Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives

by Carmen M. Galvez-Sánchez and Gustavo A. Reyes del Paso

J. Clin. Med. 2020, 9(4), 1219; https://doi.org/10.3390/jcm9041219 - 23 Apr 2020

Cited by 135 | Viewed by 26742

Abstract

Fibromyalgia syndrome (FMS) is a chronic illness characterized by widespread pain and other clinical and emotional symptoms. The lack of objective markers of the illness has been a persistent problem in FMS research, clinical management, and social recognition of the disease. A critical [...] Read more.

Fibromyalgia syndrome (FMS) is a chronic illness characterized by widespread pain and other clinical and emotional symptoms. The lack of objective markers of the illness has been a persistent problem in FMS research, clinical management, and social recognition of the disease. A critical historical revision of diagnostic criteria for FMS, especially those formulated by the American College of Rheumatology (ACR), was performed. This narrative review has been structured as follows: Introduction; historical background of FMS, including studies proposing and revising the diagnostic criteria; the process of development of the ACR FMS diagnostic criteria (1990 and 2010 versions); revisions of the 2010 ACR FMS diagnostic criteria; the development of scales based on the 2010 and 2011 criteria, which could help with diagnosis and evaluation of the clinical severity of the disease, such as the Polysymptomatic Distress Scale and the FMS Survey Questionnaire; relationships of prevalence and sex ratio with the different diagnostic criteria; validity and diagnostic accuracy of the ACR FMS criteria; the issues of differential diagnosis and comorbidity; the strength and main limitations of the ACR FMS criteria; new perspectives regarding FMS diagnosis; and the impact of the novel findings in the diagnosis of FMS. It is concluded that despite the official 2010 FMS diagnostic criteria and the diagnostic proposal of 2011 and 2016, complaints from health professionals and patients continue. Full article

(This article belongs to the Special Issue New Frontiers in the Diagnosis, Prediction, Prevention, and Management of Fibromyalgia)

► Show Figures

Graphical abstract

12 pages, 695 KiB

Open AccessArticle

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma

by Hsin-Chih Yeh, Ching-Chia Li, Sheng-Chen Wen, Nirmish Singla, Solomon L. Woldu, Haley Robyak, Chun-Nung Huang, Hung-Lung Ke, Wei-Ming Li, Hsiang-Ying Lee, Chia-Yang Li, Bi-Wen Yeh, Sheau-Fang Yang, Hung-Pin Tu, Shahrokh F. Shariat, Arthur I. Sagalowsky, Jay D. Raman, Yair Lotan, Jer-Tsong Hsieh, Vitaly Margulis and Wen-Jeng Wu Show full author list Hide full author list

J. Clin. Med. 2020, 9(4), 1218; https://doi.org/10.3390/jcm9041218 - 23 Apr 2020

Cited by 3 | Viewed by 3135

Abstract

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., [...] Read more.

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115–2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457–3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299–2.545, p = 0.0005). Kaplan–Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients’ region of presentation suggests its general applicability across different ethnicities. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

► Show Figures

Figure 1

12 pages, 5750 KiB

Open AccessArticle

Clinical and Histopathological Characteristics of Cutaneous Lymphoid Hyperplasia: A Comparative Study According to Causative Factors

by Myoung Eun Choi, Keon Hee Lee, Dong Jun Lim, Chong Hyun Won, Sung Eun Chang, Mi Woo Lee, Jee Ho Choi and Woo Jin Lee

J. Clin. Med. 2020, 9(4), 1217; https://doi.org/10.3390/jcm9041217 - 23 Apr 2020

Cited by 5 | Viewed by 3740

Abstract

Cutaneous lymphoid hyperplasia (CLH) is a heterogeneous type of reactive lymphocytic infiltration resembling cutaneous lymphoma clinically and histopathologically. Few studies describe the relationship between the causative agents and histopathological and immunohistochemical characteristics of CLH. We investigated the clinical and histopathological characteristics of 50 [...] Read more.

Cutaneous lymphoid hyperplasia (CLH) is a heterogeneous type of reactive lymphocytic infiltration resembling cutaneous lymphoma clinically and histopathologically. Few studies describe the relationship between the causative agents and histopathological and immunohistochemical characteristics of CLH. We investigated the clinical and histopathological characteristics of 50 patients with cutaneous CLH and analyzed them according to causative factors and predominant cell types (B or T cells). We retrospectively reviewed medical records to identify causative agents, and histopathological and immunohistochemical features. The majority of infiltrating lymphocytes were T cells (60%). T cell-dominant CLH showed papuloplaque lesions, whereas B cell-dominant CLH lesions were nodular. The infiltration pattern differed between T and B cells. In terms of prognosis, B-cell-predominant lesions tended to respond better to treatment than T-cell-predominant lesions. Hair dyes tended to be associated with multiple CLH lesions in older patients. CLH lesions associated with drugs were located on the head and neck. Insect bites were likely to cause a solitary papular lesion. Histopathologically, infiltration depth was located more superficially than other causes and featured intense eosinophilic infiltration. Thus, our study demonstrated that CLH presents different clinicopathological features according to causative agents and predominant lymphocytic types. Full article

(This article belongs to the Section Dermatology)

► Show Figures

Figure 1

Figure 1
The clinicopathological features according to T cell- or B cell-dominant lymphocytic infiltration. (a–f) T cell-dominant cutaneous lymphoid hyperplasia. (a) Multiple erythematous papules developed in both periauricular areas. (b) Histopathological examination revealed diffuse pandermal lymphocytic infiltration (hematoxylin and eosin stain; magnification, ×40). (c) The cells were mostly composed of small lymphohistiocytes as well as small amounts of eosinophils (hematoxylin and eosin stain; magnification, ×200). Immunohistochemical staining revealed that most lymphocytes showed positivity with (d) CD4, whereas (e) CD8 and (f) CD20 were stained in relatively smaller proportions (×40). (g–l) B-cell-dominant cutaneous lymphoid hyperplasia. (g) Multiple erythematous nodules were noted in the chest area after trauma. (h) Skin biopsy analysis showed lymphoid follicular formation in the dermis: hematoxylin and eosin stain; original magnification, ×40; (i) hematoxylin and eosin stain; original magnification, ×200. Lymphocytes were weakly positive for (j) CD4 and (k) CD8 in the immunohistochemical staining, whereas most lymphocytes were densely stained with (l) CD20 (×40). Full article ">Figure 2
The clinicopathological characteristics of cutaneous lymphoid hyperplasia after hair dye use; (a,b) The patient had multiple erythematous nodules on his face after hair dye. (c) Skin biopsy reveals nodular and follicular infiltration in the dermis: Hematoxylin-eosin stain; magnification: ×40. Lymphocytes showed weak positivity for CD4 (d) and CD8 (e), while most lymphocytes stained positive with CD20 (f) (×40). Full article ">Figure 3
The clinicopathological characteristics of arthropod-bite reaction; (a) solitary erythematous papule was noticed on the patient’s forearm. (b) Histopathological examination reveals lymphocytic infiltration mostly on the upper dermis. (c) Numerous eosinophils were observed. (b: Hematoxylin-eosin stain; magnification: ×40 c: Hematoxylin-eosin stain; magnification: ×200). Lymphocytes showed positive stains for CD4 (d) and CD8 (e) and weak positive staining for CD20 (f) (×40). Full article ">Figure 4
The clinicopathological features of trauma-associated cutaneous lymphoid hyperplasia; (a) multiple erythematous nodules were observed after injection-related trauma. (b) Biopsy specimen of the nodule reveals lymphocytic infiltration into deep dermis and subcutis (hematoxylin-eosin stain; magnification: ×20). Only small portions of lymphocytes showed positive reactivity for CD4 (c) and CD8 (d), while most lymphocytes showed positivity for CD20 (e) (×40). Full article ">Figure 5
The clinicopathological features of drug-induced cutaneous lymphoid hyperplasia. (a) Multiple erythematous papules were observed 1 month after taking new drugs. (b) Histopathological examination revealed diffuse lymphocytic infiltration in the whole dermis (hematoxylin and eosin stain; magnification, ×40). Lymphocytes were intensely stained with CD4 (c), whereas fewer than 10% of lymphocytes showed positive reactivity for CD8 (d) and CD20 (e) (×40). Full article ">

17 pages, 264 KiB

Open AccessReview

Common Musculoskeletal Disorders in the Elderly: The Star Triad

by Marco Alessandro Minetto, Alessandro Giannini, Rebecca McConnell, Chiara Busso, Guglielmo Torre and Giuseppe Massazza

J. Clin. Med. 2020, 9(4), 1216; https://doi.org/10.3390/jcm9041216 - 23 Apr 2020

Cited by 61 | Viewed by 12691

Abstract

Musculoskeletal disorders are debilitating conditions that significantly impair the state of health, especially in elderly subjects. A pathological triad of inter-related disorders that are highly prevalent in the elderly consists of the following main “components”: sarcopenia, tendinopathies, and arthritis. The aim of this [...] Read more.

Musculoskeletal disorders are debilitating conditions that significantly impair the state of health, especially in elderly subjects. A pathological triad of inter-related disorders that are highly prevalent in the elderly consists of the following main “components”: sarcopenia, tendinopathies, and arthritis. The aim of this review is to critically appraise the literature relative to the different disorders of this triad, in order to highlight the pathophysiological common denominator and propose strategies for personalized clinical management of patients presenting with this combination of musculoskeletal disorders. Their pathophysiological common denominator is represented by progressive loss of (focal or generalized) neuromuscular performance with a risk of adverse outcomes such as pain, mobility disorders, increased risk of falls and fractures, and impaired ability or disability to perform activities of daily living. The precise management of these disorders requires not only the use of available tools and recently proposed operational definitions, but also the development of new tools and approaches for prediction, diagnosis, monitoring, and prognosis of the three disorders and their combination. Full article

(This article belongs to the Special Issue Physical Activity in the Elderly and Orthopaedic Surgery)

15 pages, 679 KiB

Open AccessArticle

Association between the 2018 WCRF/AICR and the Low-Risk Lifestyle Scores with Colorectal Cancer Risk in the Predimed Study

by Laura Barrubés, Nancy Babio, Pablo Hernández-Alonso, Estefania Toledo, Judith B. Ramírez Sabio, Ramón Estruch, Emilio Ros, Montserrat Fitó, Angel M Alonso-Gómez, Miquel Fiol, Jose Lapetra, Lluís Serra-Majem, Xavier Pintó, Miguel Ruiz-Canela, Dolores Corella, Olga Castañer, Manuel Macías-González and Jordi Salas-Salvadó

J. Clin. Med. 2020, 9(4), 1215; https://doi.org/10.3390/jcm9041215 - 23 Apr 2020

Cited by 21 | Viewed by 7880

Abstract

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed [...] Read more.

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4–7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63–0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64–0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future. Full article

(This article belongs to the Section Epidemiology & Public Health)

► Show Figures

Figure 1

10 pages, 1621 KiB

Open AccessArticle

The Effects of Granulocyte Colony-Stimulating Factor in Patients with a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling: A 10-Year Follow-Up of the RIGENERA Study

by Antonio Maria Leone, Domenico D’Amario, Francesco Cannata, Francesca Graziani, Josip A. Borovac, Giuseppe Leone, Valerio De Stefano, Eloisa Basile, Andrea Siracusano, Leonarda Galiuto, Gabriella Locorotondo, Italo Porto, Rocco Vergallo, Francesco Canonico, Attilio Restivo, Antonio Giuseppe Rebuzzi and Filippo Crea

J. Clin. Med. 2020, 9(4), 1214; https://doi.org/10.3390/jcm9041214 - 23 Apr 2020

Cited by 8 | Viewed by 3285

Abstract

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order [...] Read more.

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment. Full article

(This article belongs to the Special Issue Therapies for Myocardial Injury and Infarction)

► Show Figures

Figure 1

Journal Menu

Journal Browser

J. Clin. Med., Volume 9, Issue 4 (April 2020) – 350 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI