Journal of Clinical Medicine

9 pages, 266 KiB

Open AccessArticle

Phosphatidylethanol for Monitoring Alcohol Use in Liver Transplant Candidates: An Observational Study

by Pablo Barrio, Antoni Gual, Anna Lligoña, Lidia Teixidor, Wolfgang Weinmann, Michel Yegles and Friedrich M. Wurst

J. Clin. Med. 2020, 9(9), 3060; https://doi.org/10.3390/jcm9093060 - 22 Sep 2020

Cited by 11 | Viewed by 3877

Abstract

Liver transplantation remains an essential procedure for many patients suffering from alcoholic liver disease. Alcohol use monitoring remains paramount all through the stages of this complex process. Direct alcohol biomarkers, with improved specificity and sensibility, should replace traditional indirect markers. Phosphatidylethanol (PEth) has [...] Read more.

Liver transplantation remains an essential procedure for many patients suffering from alcoholic liver disease. Alcohol use monitoring remains paramount all through the stages of this complex process. Direct alcohol biomarkers, with improved specificity and sensibility, should replace traditional indirect markers. Phosphatidylethanol (PEth) has been recently tested in alcoholic liver disease patients, but more evidence is needed, especially in comparison with other direct biomarkers. We conducted an observational study among patients awaiting liver transplantation. We analyzed Peth in blood, ethylglucuronide (EtG) in hair and urine and ethylsulphate (EtS) in urine, using mass spectrometry methods. In addition, transaminases, and self-reports were analyzed. A total of 50 patients were included (84% men, mean age 59 years (SD = 6)). 18 patients (36%) screened positive for any marker. Self-reports were positive in 3 patients. EtS was the biomarker with more positive screens. It also was the most frequently exclusive biomarker, screening positive in 7 patients who were negative for all other biomarkers. PEth was positive in 5 patients, being the only positive biomarker in 2 patients. It showed a false negative in a patient admitting alcohol use the previous week and screening positive for EtG and EtS. Hair EtG was positive in 3 patients who had negative Peth, EtG. EtG did not provide any exclusive positive result.A combination of biomarkers seems to be the best option to fully ascertain abstinence in this population. Our study suggest EtS might also play a significant role. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

► Show Figures

Figure 1

10 pages, 285 KiB

Open AccessArticle

Impact of Psychological Distress and Sleep Quality on Balance Confidence, Muscle Strength, and Functional Balance in Community-Dwelling Middle-Aged and Older People

by Raquel Fábrega-Cuadros, Agustín Aibar-Almazán, Antonio Martínez-Amat and Fidel Hita-Contreras

J. Clin. Med. 2020, 9(9), 3059; https://doi.org/10.3390/jcm9093059 - 22 Sep 2020

Cited by 7 | Viewed by 3025

Abstract

The objective was to evaluate the associations of psychological distress and sleep quality with balance confidence, muscle strength, and functional balance among community-dwelling middle-aged and older people. An analytical cross-sectional study was conducted (n = 304). Balance confidence (Activities-specific Balance Confidence scale, [...] Read more.

The objective was to evaluate the associations of psychological distress and sleep quality with balance confidence, muscle strength, and functional balance among community-dwelling middle-aged and older people. An analytical cross-sectional study was conducted (n = 304). Balance confidence (Activities-specific Balance Confidence scale, ABC), muscle strength (hand grip dynamometer), and functional balance (Timed Up-and-Go test) were assessed. Psychological distress and sleep quality were evaluated by the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index, respectively. Age, sex, physical activity level, nutritional status, and fatigue were included as possible confounders. Multivariate linear and logistic regressions were performed. Higher values of anxiety (OR = 1.10), fatigue (OR = 1.04), and older age (OR = 1.08) were associated with an increased risk of falling (ABC < 67%). Greater muscle strength was associated with male sex and improved nutritional status (adjusted R² = 0.39). On the other hand, being older and using sleeping medication were linked to poorer functional balance (adjusted R² = 0.115). In conclusion, greater anxiety levels and the use of sleep medication were linked to a high risk of falling and poorer functional balance, respectively. No associations were found between muscle strength and sleep quality, anxiety, or depression. Full article

(This article belongs to the Special Issue Prevention and Treatment of Sarcopenia)

19 pages, 3094 KiB

Open AccessArticle

Motor Control Stabilisation Exercise for Patients with Non-Specific Low Back Pain: A Prospective Meta-Analysis with Multilevel Meta-Regressions on Intervention Effects

by Daniel Niederer, Tilman Engel, Lutz Vogt, Adamantios Arampatzis, Winfried Banzer, Heidrun Beck, María Moreno Catalá, Michael Brenner-Fliesser, Claas Güthoff, Thore Haag, Alexander Hönning, Ann-Christin Pfeifer, Petra Platen, Marcus Schiltenwolf, Christian Schneider, Katharina Trompeter, Pia-Maria Wippert and Frank Mayer

J. Clin. Med. 2020, 9(9), 3058; https://doi.org/10.3390/jcm9093058 - 22 Sep 2020

Cited by 23 | Viewed by 7115

Abstract

Low-to-moderate quality meta-analytic evidence shows that motor control stabilisation exercise (MCE) is an effective treatment of non-specific low back pain. A possible approach to overcome the weaknesses of traditional meta-analyses would be that of a prospective meta-analyses. The aim of the present analysis [...] Read more.

Low-to-moderate quality meta-analytic evidence shows that motor control stabilisation exercise (MCE) is an effective treatment of non-specific low back pain. A possible approach to overcome the weaknesses of traditional meta-analyses would be that of a prospective meta-analyses. The aim of the present analysis was to generate high-quality evidence to support the view that motor control stabilisation exercises (MCE) lead to a reduction in pain intensity and disability in non-specific low back pain patients when compared to a control group. In this prospective meta-analysis and sensitivity multilevel meta-regression within the MiSpEx-Network, 18 randomized controlled study arms were included. Participants with non-specific low back pain were allocated to an intervention (individualized MCE, 12 weeks) or a control group (no additive exercise intervention). From each study site/arm, outcomes at baseline, 3 weeks, 12 weeks, and 6 months were pooled. The outcomes were current pain (NRS or VAS, 11 points scale), characteristic pain intensity, and subjective disability. A random effects meta-analysis model for continuous outcomes to display standardized mean differences between intervention and control was performed, followed by sensitivity multilevel meta-regressions. Overall, 2391 patients were randomized; 1976 (3 weeks, short-term), 1740 (12 weeks, intermediate), and 1560 (6 months, sustainability) participants were included in the meta-analyses. In the short-term, intermediate and sustainability, moderate-to-high quality evidence indicated that MCE has a larger effect on current pain (SMD = −0.15, −0.15, −0.19), pain intensity (SMD = −0.19, −0.26, −0.26) and disability (SMD = −0.15, −0.27, −0.25) compared with no exercise intervention. Low-quality evidence suggested that those patients with comparably intermediate current pain and older patients may profit the most from MCE. Motor control stabilisation exercise is an effective treatment for non-specific low back pain. Sub-clinical intermediate pain and middle-aged patients may profit the most from this intervention. Full article

(This article belongs to the Special Issue Improved Rehabilitation for Patients with Chronic Pain)

► Show Figures

Figure 1

Figure 1
Participants’ flow. Full article ">Figure 2
Data and Forest plots for the pooled outcome estimates for the short-term effects of motor control stabilisation exercise vs. no additional exercise. (A): current pain intensity; (B): characteristic pain intensity; (C): disability; MCS, multicenter study; SCS; single-center study; A–F are the single study sites; a stands for MCE, b for MCE + behavioral. SD, standard deviation; P, p-value; IV, inverse variance; CI, confidence intervals; experimental, motor control stabilisation group. Full article ">Figure 3
Data and Forest plots for the pooled outcome estimates for the mid-term effects of motor control stabilisation exercise vs. no additional exercise. (A): current pain intensity; (B): characteristic pain intensity; (C): disability; MCS equals multicenter study; SCS equals single-center study, A–F are the single study sites; a stands for MCE, b for MCE + behavioral. SD, standard deviation; P, p-value; IV, inverse variance; CI, confidence intervals; experimental, motor control stabilisation group. Full article ">Figure 4
Data and Forest plots for the pooled outcome estimates for the long-term/sustainability effects of motor control stabilisation exercise vs. no additional exercise. (A): current pain intensity; (B): characteristic pain intensity; (C): disability. MCS equals multicenter study; SCS equals single-center study, A–F are the single study sites; a stands for MCE, b for MCE + behavioral. SD, standard deviation; P, p-value; IV, inverse variance; CI, confidence intervals; experimental, motor control stabilisation group. Full article ">Figure 5
Bubble plots of the meta-regressions (single predictor). (A) current pain intensity at baseline and (B) participants mean age at baseline on the effect size estimator of the mid-term effect (12 weeks) on disability. The size of the bubble illustrates the weighting of the respective study arm by inverse variance. Full article ">

26 pages, 924 KiB

Open AccessReview

Contributions of Major Cell Populations to Sjögren’s Syndrome

by Richard Witas, Shivai Gupta and Cuong Q. Nguyen

J. Clin. Med. 2020, 9(9), 3057; https://doi.org/10.3390/jcm9093057 - 22 Sep 2020

Cited by 29 | Viewed by 5609

Abstract

Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The [...] Read more.

Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The etiology of SS remains poorly understood, yet progress has been made in identifying progressive stages of disease using preclinical mouse models. The roles played by immune cell subtypes within these stages of disease are becoming increasingly well understood, though significant gaps in knowledge still remain. There is evidence for distinct involvement from both innate and adaptive immune cells, where cells of the innate immune system establish a proinflammatory environment characterized by a type I interferon (IFN) signature that facilitates propagation of the disease by further activating T and B cell subsets to generate autoantibodies and participate in glandular destruction. This review will discuss the evidence for participation in disease pathogenesis by various classes of immune cells and glandular epithelial cells based upon data from both preclinical mouse models and human patients. Further examination of the contributions of glandular and immune cell subtypes to SS will be necessary to identify additional therapeutic targets that may lead to better management of the disease. Full article

(This article belongs to the Special Issue Diseases of the Salivary Glands)

► Show Figures

Figure 1

Figure 1
Proposed functions of different cell types in the pathogenesis of Sjögren’s syndrome (SS). (1) The initiating events in the development of SS remain unclear, but evidence suggests the disease proceeds following an environmental trigger on a susceptible genetic background, likely a viral infection. (2) Salivary gland epithelia cells (SGECs) experience increased apoptosis and act as sources of inflammatory cytokines and chemokines within the salivary gland (SG). (3) CD8+ T cells are poorly understood in SS, but may contribute to tissue destruction in the glands. (4) Macrophages participate in tissue destruction through the release of proteases and cytokines and display reduced efferocytosis allowing unremoved apoptotic cells to act as sources of self-antigen. (5) Type I interferon (T1-IFN) both initiates antiviral activity and exerts an activating effect on cells of the immune system. T1-IFN is produced by multiple cell types but is closely associated with plasmacytoid DCs (pDCs). (6) Myeloid dendritic cells (mDCs) are the dominant antigen presenting cells to T cells, however, macrophages and SGECs also participate. (7) Antigen presentation allows for activation of CD8+ T cells and the Th1, Th2, and Th17 CD4+ T cell subsets, which can then contribute to various aspects of the disease pathology. Th1 cells enter the glands and compose much of the early infiltrates and exacerbate the inflammatory environment with the production of type II interferon, while Th17 cells play an increasingly well recognized role in SS as sources of cytokines including IL-17. Conflicting evidence has caused the roles of regulatory T cells (Tregs) remain indistinct in SS. Th2 cells support the humoral autoimmune response through cytokines incusing IL-4. (8 and 9) T follicular helper (Tfh) cells support B cell development in germinal centers (GC) that include follicular dendritic cell (fDC) networks. Germinal centers exist in the spleen, but about 25% of SS patients develop ectopic germinal centers in the SG containing Tfh and fDC. B cells in the germinal center undergo proliferation, somatic hypermutation and affinity hypermutation in the dark zone of the germinal center. (10) B cells then proceed to germinal center selection by fDCs in the light zone and either leave the germinal center as memory B cells or antibody producing plasma cells (Fate 1), or return to the dark zone for further affinity maturation (Fate 2). (11) The MZ B cells function as part of the adaptive immune system carrying antigens to the germinal centers for more efficient generation of memory B cells and glandular MZB cells are proliferative, activated, and produce autoantibodies. Lastly, (12) plasma cells exhibit hyperactivity and are responsible for the production of pathogenic autoantibodies. Created with BioRender.com. Full article ">

13 pages, 1317 KiB

Open AccessArticle

Characterization of Fetal Thyroid Levels at Delivery among Appalachian Infants

by Madison N. Crank, Jesse N. Cottrell, Brenda L. Mitchell and Monica A. Valentovic

J. Clin. Med. 2020, 9(9), 3056; https://doi.org/10.3390/jcm9093056 - 22 Sep 2020

Cited by 4 | Viewed by 2542

Abstract

Thyroid disorders are a frequently encountered issue during pregnancy and a cause of maternal and fetal morbidity. In regions like Appalachia that are particularly susceptible to health disparities, descriptive studies are needed to assist in identifying pathologic derangements. We sought to characterize fetal [...] Read more.

Thyroid disorders are a frequently encountered issue during pregnancy and a cause of maternal and fetal morbidity. In regions like Appalachia that are particularly susceptible to health disparities, descriptive studies are needed to assist in identifying pathologic derangements. We sought to characterize fetal thyroid hormone levels at delivery and investigate whether or not maternal demographic characteristics affect the prevalence of neonatal thyroid disease. A cross-sectional analysis was conducted on 130 pregnant women recruited from the Tri-State region, incorporating areas of Kentucky, Ohio, and West Virginia. Total triiodothyronine (T3) (p = 0.4799), free T3 (p = 0.6323), T3 uptake (p = 0.0926), total thyroxine (T4) (p = 0.8316), free T4 (p = 0.0566), and Thyroid stimulating hormone (TSH) (p = 0.8745) levels were comparable between urban and rural newborns. We found no effect of hypertension status or nicotine levels on fetal umbilical cord thyroid hormone levels. Maternal diabetic status was associated with lower T4 (p = 0.0099) and free T4 (p = 0.0025) levels. Cotinine affected levels of T4 (p = 0.0339). In regard to maternal Body Mass Index (BMI), there was an increase in total T3 as BMI increased (p = 0.0367) and no significant difference in free T3, T3 uptake, T4, free T4, or TSH. There was a negative correlation between TSH and 1 min Apgar scores (p = 0.0058). Lead and cadmium have been implicated to alter TSH levels, but no correlation was found in our study (r² = 0.0277). There were no differences in cord blood between urban (37.3 ± 10.3 fmol/ug DNA) and rural (70.5 ± 26.8 fmol/ug DNA) benzo(a)pyrene DNA adducts (p = 0.174). Thyroid disorders present a unique opportunity for the prevention of perinatal morbidity and mortality, since maternal treatment, as well as maternal demographic characteristics, can have direct fetal effects. Full article

(This article belongs to the Section Obstetrics & Gynecology)

► Show Figures

Figure 1

14 pages, 741 KiB

Open AccessArticle

The Frequency of, and Factors Associated with Prolonged Hospitalization: A Multicentre Study in Victoria, Australia

by Richard Ofori-Asenso, Danny Liew, Johan Mårtensson and Daryl Jones

J. Clin. Med. 2020, 9(9), 3055; https://doi.org/10.3390/jcm9093055 - 22 Sep 2020

Cited by 21 | Viewed by 3459

Abstract

Background: Limited available evidence suggests that a small proportion of inpatients undergo prolonged hospitalization and use a disproportionate number of bed days. Understanding the factors contributing to prolonged hospitalization may improve patient care and reduce the length of stay in such patients. Methods: [...] Read more.

Background: Limited available evidence suggests that a small proportion of inpatients undergo prolonged hospitalization and use a disproportionate number of bed days. Understanding the factors contributing to prolonged hospitalization may improve patient care and reduce the length of stay in such patients. Methods: We undertook a retrospective cohort study of adult (≥20 years) patients admitted for at least 24 h between 14 November 2016 and 14 November 2018 to hospitals in Victoria, Australia. Data including baseline demographics, admitting specialty, survival status and discharge disposition were obtained from the Victorian Admission Episode Dataset. Multivariable logistic regression analysis was used to identify factors independently associated with prolonged hospitalization (≥14 days). Cox proportional hazard regression model was used to examine the association between various factors and in-hospital mortality. Results: There were almost 5 million hospital admissions over two years. After exclusions, 1,696,112 admissions lasting at least 24 h were included. Admissions with prolonged hospitalization comprised only 9.7% of admissions but utilized 44.2% of all hospital bed days. Factors independently associated with prolonged hospitalization included age, female gender, not being in a relationship, being a current smoker, level of co-morbidity, admission from another hospital, admission on the weekend, and the number of admissions in the prior 12 months. The in-hospital mortality rate was 5.0% for those with prolonged hospitalization compared with 1.8% in those without (p < 0.001). Prolonged hospitalization was also independently associated with a decreased likelihood of being discharged to home (OR 0.53, 95% CI 0.52–0.54). Conclusions: Patients experiencing prolonged hospitalization utilize a disproportionate proportion of bed days and are at higher risk of in-hospital death and discharge to destinations other than home. Further studies are required to identify modifiable factors contributing to prolonged hospitalization as well as the quality of end-of-life care in such admissions. Full article

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

► Show Figures

Figure 1

12 pages, 1018 KiB

Open AccessArticle

Evaluation of an Amino Acid Mix on the Secretion of Gastrointestinal Peptides, Glucometabolic Homeostasis, and Appetite in Obese Adolescents Administered with a Fixed-Dose or ad Libitum Meal

by Antonello E. Rigamonti, Sofia Tamini, Sabrina Cicolini, Alessandra De Col, Diana Caroli, Stefania Mai, Eugenia Rondinelli, Antonella Saezza, Silvano G. Cella and Alessandro Sartorio

J. Clin. Med. 2020, 9(9), 3054; https://doi.org/10.3390/jcm9093054 - 22 Sep 2020

Cited by 6 | Viewed by 2582

Abstract

Proteins have been demonstrated to reduce food intake in animals and humans via peripheral and central mechanisms. Supplementation of a dietetic regimen with single or mixed amino acids might represent an approach to improve the effectiveness of any body weight reduction program in [...] Read more.

Proteins have been demonstrated to reduce food intake in animals and humans via peripheral and central mechanisms. Supplementation of a dietetic regimen with single or mixed amino acids might represent an approach to improve the effectiveness of any body weight reduction program in obese subjects. The aim of the present study was to evaluate the effects of an amino acid mix (L-arginine + L-leucine + L-glutamine + L-tryptophan) on the secretion of some gastrointestinal peptides (i.e., ghrelin and glucagon-like peptide type 1, GLP-1), glucometabolic homeostasis (i.e., glucose, insulin, and glucagon), and appetite (hunger/satiety scored by visual analogue scale, VAS) in obese adolescents (n = 14; 10 females and 4 males; age: 16.6 ± 1.0 years; body mass index (BMI): 36.4 ± 4.6 kg/m²; fat-free mass (FFM): 54.9 ± 4.7%; fat mass (FM): 45.1 ± 4.4%) administered with a fixed-dose (lunch) or ad libitum (dinner) meal. Isocaloric maltodextrins were used as control treatment. During the lunch test, a significant increase in circulating levels of GLP-1, but not of ghrelin, was observed in the amino acid-treated group, which was congruent with significant changes in appetite, i.e., increase in satiety and decrease in hunger. A significant hyperglycemia was found in the maltodextrin-treated group during the prelunch period, without any significant changes in insulin and glucagon between the two groups. During the dinner test, there were no significant differences in appetite (hunger/satiety) and intake of calories. In conclusion, L-arginine, L-leucine, L-glutamine, and L-tryptophan, when administered to obese adolescents with a fixed-dose meal, are capable of evoking an anorexigenic response, which is, at least in part, mediated by an increase in GLP-1 released in circulation by L cells, which are capable of chemosensing specific amino acids present in the intestinal lumen. Further additional studies are requested to understand whether higher doses are necessary to inhibit ad libitum feeding. Full article

(This article belongs to the Section Endocrinology & Metabolism)

► Show Figures

Figure 1

Figure 1
Overview of the experimental protocol. VAS: visual analogue scale. Full article ">Figure 2
Changes in circulating levels of glucagon-like peptide type 1 (GLP-1 (top panel)) and ghrelin (bottom panel) in obese adolescents after a fixed-dose lunch (completely consumed within 15 min starting at T75), administered with amino acid mix (L-arginine, L-leucine, L-glutamine, and L-tryptophan) or placebo (maltodextrins) at T0. See the text for further details. Values are expressed as means ± standard deviations (SDs). The number of subjects was 14. * p < 0.05 vs. the corresponding T0 value; × p < 0.05 vs. the value in the maltodextrin-treated group at the corresponding time point. A two-way ANOVA with repeated measures (with the two factors time and group and the interaction time × group) followed by the post hoc Tukey’s test was used. Full article ">Figure 3
Changes in VAS ratings of satiety (top panel) and hunger (bottom panel) in obese adolescents after a fixed-dose lunch (completely consumed within 15 min starting at T75) or ad libitum dinner (within 20 min starting at T630), administered with amino acid mix (L-arginine, L-leucine, L-glutamine, and L-tryptophan) or placebo (maltodextrins) at T0 for the lunch test and at T555 for the dinner test. See the text for further details. Values are expressed as means ± SDs. The number of subjects was 14. * p < 0.05 vs. the corresponding T0 or T630 value; × p < 0.05 vs. the value in the maltodextrin-treated group at the corresponding time point. A two-way ANOVA with repeated measures (with the two factors time and group and the interaction time × group) followed by the post hoc Tukey’s test was used. Full article ">Figure 4
Changes of circulating levels of glucose (top panel), insulin (middle panel), and glucagon (bottom panel) in obese adolescents after a fixed-dose lunch (completely consumed within 15 min starting at T75) administered with amino acid mix (L-arginine, L-leucine, L-glutamine, and L-tryptophan) or placebo (maltodextrins) at T0. See the text for further details. Values are expressed as means ± SDs. The number of subjects was 14. * p < 0.05 vs. the corresponding T0 value; × p < 0.05 vs. the value in the maltodextrin-treated group at the corresponding time point. A two-way ANOVA with repeated measures (with the two factors time and group and the interaction time × group) followed by the post hoc Tukey’s test was used. Full article ">Figure 5
Intake of calories of food (i.e., difference between pre- and postdinner values) in obese adolescents after ad libitum dinner (consumed within 20 min starting at T555), administered with amino acid mix (L-arginine, L-leucine, L-glutamine, and L-tryptophan) or placebo (maltodextrins) at T0. See the text for further details. Values are expressed as means ± SDs. The number of subjects was 14. A Student’s t-test for paired data was used. Full article ">

12 pages, 2422 KiB

Open AccessArticle

Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation

by Mark Slevin, Elisa García-Lara, Bogdan Capitanescu, Coral Sanfeliu, Yasmin Zeinolabediny, Raid AlBaradie, Peter Olah, Baoqiang Guo, Daniel Pirici, Mario Di Napoli and Aurel Popa-Wagner

J. Clin. Med. 2020, 9(9), 3053; https://doi.org/10.3390/jcm9093053 - 22 Sep 2020

Cited by 20 | Viewed by 3687

Abstract

Background: We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the capacity of mCRP to travel [...] Read more.

Background: We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the capacity of mCRP to travel to or appear at other locations within the brain that might account for later chronic neuroinflammatory or neurodegenerative effects. Methods: Immunohistochemistry was performed on Formalin-fixed, paraffin-embedded archived brain tissue blocks obtained at autopsy from stroke patients and age-matched controls. We modelled mCRP migration into the brain after haemorrhagic stroke by infusing mCRP (3.5 µg) into the hippocampus of mice and localized mCRP with histological and immunohistochemistry methods. Results: On human tissue in the early stages of haemorrhage, there was no staining of mCRP. However, with increasing post-stroke survival time, mCRP immunostaining was associated with some parenchymal brain cells, some stroke-affected neurons in the surrounding areas and the lumen of large blood vessels as well as brain capillaries. Further from the peri-haematoma region, however, mCRP was detected in the lumen of micro-vessels expressing aquaporin 4 (AQP4). In the hypothalamus, we detected clusters of neurons loaded with mCRP along with scattered lipofuscin-like deposits. In the peri-haematoma region of patients, mCRP was abundantly seen adjacent to AQP4 immunoreactivity. When we stereotactically injected mCRP into the hippocampus of mice, we also observed strong expression in distant neurones of the hypothalamus as well as cortical capillaries. Conclusions: mCRP is abundantly expressed in the brain after haemorrhagic stroke, directly impacting the pathophysiological development of the haematoma. In addition, it may have indirect effects, where the microcirculatory system appears to be able to carry it throughout the cortex as far as the hypothalamus, allowing for long-distance effects and damage through its capacity to induce inflammation and degenerate neuronal perivascular compartments. Full article

(This article belongs to the Special Issue Stroke Life Style: Advancing Our Understanding of Disease Mechanism and Therapy)

► Show Figures

Figure 1

Figure 1
Monomeric C-reactive protein (mCRP) and aquaporin 4 (AQP4) expression pattern in the perihaematomal area. (A) In the haemorrhagic stroke area of early deaths (<48 h), mCRP was seen in numerous microvessels, while AQP4 immunoreactivity was localized adjacent to the mCRP staining and lined up with the haemorrhagic core. However, with increasing post-stroke survival time, mCRP immunostaining was detected in the lumen of microvessels expressing AQP4 (B, arrows) and some parenchymal brain cells and some stroke-affected neurons in the surrounding areas (C, arrowheads) and the lumen of large blood vessels (C, arrow) and brain capillaries (C, inset). In the normal areas of the brain, there was a weak cytoplasmic expression of mCRP in cortical neurons (C). A quantification of the cellular area covered by mCRP- and AQP4-positive cells revealed that mCRP-positive cell staining was predominant in the perihaematomal area, while AQP4-positive structures populated areas in the perihaematomal area followed by penumbra and, to a lesser extent, in controls. Occasionally, in the normal areas of the brain, there was a weak cytoplasmic expression of mCRP in cortical neurons (D). Colocalized mCRP/AQP4 cells were found only in the perihaematomal area (E). Scale bars are 100 µm and 20 µm for DAB staining. *** p = 0.001. In the figure legend, CRP indicates mCRP; Aqua4, AQP4. Full article ">Figure 2
Glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression pattern in the perihaematomal area Many reactive astrocytes expressing AQP4 were detected in the proximity of large haematomas areas (A). Perihaematomal areas were populated mostly with reactive astrocytes on a background of diffuse aquaporine4 immunostaining (B, green). In controls, astrocytes and AQP4 were codistributed on blood vessels and astrocytes having a normal morphology (C and inset). A quantification of the cellular area covered by GFAP- and AQP4-positive cells revealed that AQP4-positive cells were predominant in the perihaematomal area, followed by colocalized GFAP/AQP4 structures (D). *** p = 0.001. In the figure legend, Aqua4 indicates AQP4. Full article ">Figure 3
In some samples, within a certain stage (<24 h) of haemorrhage development, strong staining was observed within capillary endothelial cells, especially within the haemorrhagic area (A,B; arrows). In severely damaged areas, mCRP was more strongly observed (C, arrows), associated within the infiltrating macrophages and inflammatory cells (C, arrowheads). We also detected clusters of neurons loaded with mCRP (D, arrows) along with scattered lipofuscin-like deposits (D, arrowheads). Full article ">Figure 4
In our stereotactically mCRP-injected murine model, we observed the pattern of mCRP distribution after 4 weeks. We found no evidence of mCRP staining in control mice (A,D), and a strong hippocampal staining of neurons in mCRP injected mice (E) adjacent to the injection site. (C) Many medium and small cortical vessels became positively stained for mCRP (B), and hypothalamic neurons became positively stained in the cytoplasm of mCRP-treated mice (F). The inset in (C) shows the isotype IgG control. Abbreviations: DG indicates dentate gyrus of the hippocampal formation, BV, blood vessels; CX, cerebral cortex; HC, hippocampus; HT, hypothalamus. Full article ">

13 pages, 964 KiB

Open AccessArticle

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features

by Álvaro Flores-Martinez, Eva Venegas-Moreno, Elena Dios, Pablo Remón-Ruiz, Noelia Gros-Herguido, M. Carmen Vázquez-Borrego, Ainara Madrazo-Atutxa, Miguel A. Japón, Ariel Kaen, Eugenio Cárdenas-Valdepeñas, Florinda Roldán, Justo P. Castaño, Raúl M. Luque, David A. Cano and Alfonso Soto-Moreno

J. Clin. Med. 2020, 9(9), 3052; https://doi.org/10.3390/jcm9093052 - 22 Sep 2020

Cited by 10 | Viewed by 2990

Abstract

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST_1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. [...] Read more.

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST_1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST_1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST_1-5 expression was also evaluated by immunohistochemistry. SST₃ was the predominant SST subtype detected, followed by SST₂, SST₅, and SST₁. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST₂ and SST₅. No major association between SST_s and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs. Full article

(This article belongs to the Special Issue From Molecules to Disease: Research and Clinical Advances in Pituitary and Neuroendocrine Tumors)

► Show Figures

Figure 1

Figure 1
Somatostatin receptors (SSTs) and dopamine receptors (DRDs) expression in NFPTs. Expression profile of SSTs and DRDs in: (A) NFPTs, gonadotropin-storing adenomas, null cell adenomas and silent corticotroph adenomas; (B) only in gonadotropin-storing adenomas; (C) only in null cell adenomas; and, (D) only in silent corticotroph adenomas. mRNA expression levels were measured by quantitative RT-PCR. Copy numbers of each transcript was adjusted by the expression levels of a control gene (ACTB). Data are shown as mean ± SEM. Full article ">Figure 2
Immunohistochemical detection of somatostatin receptors (SSTs) in NFPTs assessed by immunohistochemistry. (A) Representative pictures of SST2, SST3 and SST5 immunohistochemical scores in NFPTs. Score 1, no or only cytoplasmic immunoreactivity; score 2, membranous immunoreactivity in less than 50% of cells; score 3, membranous immunoreactivity in more than 50% of cells. Scale bar: 50 μm. (B) Percentage of NFPTs for immunohistochemistry (IHC) scores (SST2, SST3 and SST5). Full article ">Figure 3
Accumulation of E-cadherin in NFPTs assessed by immunohistochemistry. (A) Representative pictures of E-cadherin immunohistochemical scores in NFPTs. Score 1, no or very low immunoreactivity; score 2, membranous immunoreactivity in less than 50% of cells; score 3, membranous immunoreactivity in more than 50% of cells. Scale bar: 100 μm. (B) Percentage of NFPTs for IHC scores. Score 1: 9.47%; score 2: 50.52% and score 3: 40%. Full article ">

15 pages, 1786 KiB

Open AccessArticle

Syndecan-4 as a Marker of Endothelial Dysfunction in Patients with Resistant Hypertension

by Mark Lipphardt, Hassan Dihazi, Jens-Holger Maas, Ann-Kathrin Schäfer, Saskia I. Amlaz, Brian B. Ratliff, Michael J. Koziolek and Manuel Wallbach

J. Clin. Med. 2020, 9(9), 3051; https://doi.org/10.3390/jcm9093051 - 22 Sep 2020

Cited by 15 | Viewed by 3124

Abstract

(1) Background: Arterial hypertension (HTN) is one of the most relevant cardiovascular risk factors. Nowadays multiple pharmaceutical treatment options exist with novel interventional methods (e.g., baroreflex activation therapy (BAT)) as a last resort to treat patients with resistant HTN. Although pathophysiology behind resistant [...] Read more.

(1) Background: Arterial hypertension (HTN) is one of the most relevant cardiovascular risk factors. Nowadays multiple pharmaceutical treatment options exist with novel interventional methods (e.g., baroreflex activation therapy (BAT)) as a last resort to treat patients with resistant HTN. Although pathophysiology behind resistant HTN is still not fully understood. There is evidence that selected biomarkers may be involved in the pathophysiology of HTN. (2) Methods: We investigated serum SDC4-levels in patients suffering from resistant HTN before and 6 months after BAT implantation. We collected 19 blood samples from patients with resistant HTN and blood pressure above target and measured serum SDC4-levels. (3) Results: Our results showed high serum SDC4-levels in patients with resistant HTN as compared to a healthy population. Patients with both, resistant HTN and diabetes mellitus type II, demonstrated higher serum SDC4-levels. β-blockers had lowering effects on serum SDC4-levels, whereas calcium channel blockers were associated with higher levels of serum SDC4. BAT implantation did not lead to a significant difference in serum SDC4-levels after 6 months of therapy. (4) Conclusion: Based on our results we propose SDC4 is elevated in patients suffering from resistant HTN. Thus, SDC4 might be a potential marker for endothelial dysfunction in patients with resistant hypertension. Full article

(This article belongs to the Special Issue Cardiovascular and Renal Damage in Hypertension: Prognostic Role and a Guide for Treatment)

► Show Figures

Figure 1

Figure 1
Serum syndecan-4 (SDC4) level is increased in patients with resistant arterial hypertension (HTN). Values are given as means ± standard error of the mean (SEM). Full article ">Figure 2
(A): Patients who do not suffer from diabetes mellitus (DM) type II show lower levels of serum SDC4 as compared to patients with concomitant DM type II. (B): HLP does not show an association with serum SDC4-levels. (C): Smoking does not alter serum SDC4-levels. Values are given as means ± SEM. Full article ">Figure 3
(A): No significant difference in serum SDC4-level regarding CKD. However, 6 months after baroreflex activation therapy (BAT) implantation a moderate correlation is seen in patients with no CKD in their history, having lower levels of serum SDC4 as compared to patients with a positive history of CKD (p = 0.15). (B): The serum creatinine-level does not correlate with the serum SDC4-level. Values are given as means ± SEM. Full article ">Figure 4
(A): Six months after BAT implantation patients with a proteinuria >150 mg/L show higher levels of serum SDC4. (B): Serum SDC4-levels do not correspond to albuminuria of patients suffering from resistant HTN. First number of n represents patient number before BAT. Second number of n represents patient number 6 months after BAT implantation. Values are given as means ± SEM. Full article ">Figure 5
(A): Both angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers (ARBs) show no correlation to serum SDC4-levels. (B): With no β-blocker treatment SDC4-levels are significantly higher as compared to treatment with β-blockers. (C): Treatment with calcium channel blockers is associated with increased serum SDC4-levels. (D): α-blockers do not alter serum SDC4-levels. The first number of n represents patient numbers before BAT. Second number of n represents patient number 6 months after BAT implantation. If there is only one number of n mentioned, it means that the number of patients taking that medication has not changed after the 6-month interval. Values are given as means ± SEM. Full article ">Figure 6
(A): Loop diuretics do not correspond to serum SDC4-levels. (B): Treatment with thiazide diuretics reveals lower serum SDC4-levels. The first number of n represents patient numbers before BAT. Second number of n represents patient number 6 months after BAT implantation. Values are given as means ± SEM. Full article ">

13 pages, 3014 KiB

Open AccessArticle

Uninterrupted Dabigatran Administration Provides Greater Inhibition against Intracardiac Activation of Hemostasis as Compared to Vitamin K Antagonists during Cryoballoon Catheter Ablation of Atrial Fibrillation

by Zsuzsa Bagoly, Orsolya Hajas, Réka Urbancsek, Alexandra Kiss, Edit Fiak, Ferenc Sarkady, Noémi Klára Tóth, Rita Orbán-Kálmándi, Kitti Bernadett Kovács, László Nagy, Attila Nagy, János Kappelmayer, László Csiba and Zoltán Csanádi

J. Clin. Med. 2020, 9(9), 3050; https://doi.org/10.3390/jcm9093050 - 22 Sep 2020

Cited by 3 | Viewed by 2666

Abstract

Background. Cerebral thromboembolism is a rare but feared complication of transcatheter ablation in patients with atrial fibrillation (AF). Here, we aimed to test which pre-procedural anticoagulation strategy results in less intracardiac activation of hemostasis during ablation. Patients and methods. In this observational study, [...] Read more.

Background. Cerebral thromboembolism is a rare but feared complication of transcatheter ablation in patients with atrial fibrillation (AF). Here, we aimed to test which pre-procedural anticoagulation strategy results in less intracardiac activation of hemostasis during ablation. Patients and methods. In this observational study, 54 paroxysmal/persistent AF patients undergoing cryoballoon ablation were grouped according to their periprocedural anticoagulation strategy: no anticoagulation (oral anticoagulation (OAC) free; n = 24), uninterrupted vitamin K antagonists (VKA) (n = 11), uninterrupted dabigatran (n = 17). Blood was drawn from the left atrium before and immediately after the ablation procedure. Cryoablations were performed according to standard protocols, during which heparin was administered. Heparin-insensitive markers of hemostasis and endothelial damage were tested from intracardiac samples: D-dimer, quantitative fibrin monomer (FM), plasmin-antiplasmin complex (PAP), von Willebrand factor (VWF) antigen, chromogenic factor VIII (FVIII) activity. Results. D-dimer increased significantly in all groups post-ablation, with lowest levels in the dabigatran group (median [interquartile range]: 0.27 [0.36] vs. 1.09 [1.30] and 0.74 [0.26] mg/L in OAC free and uninterrupted VKA groups, respectively, p < 0.001). PAP levels were parallel to this observation. Post-ablation FM levels were elevated in OAC free (26.34 [30.04] mg/L) and VKA groups (10.12 [16.01] mg/L), but remained below cut-off in all patients on dabigatran (3.98 [2.0] mg/L; p < 0.001). VWF antigen and FVIII activity increased similarly post-ablation in all groups, suggesting comparable procedure-related endothelial damage. Conclusion. Dabigatran provides greater inhibition against intracardiac activation of hemostasis as compared to VKAs during cryoballoon catheter ablation. Full article

(This article belongs to the Special Issue Thrombosis, Blood Clotting and Vascular Biology)

► Show Figures

Figure 1

Figure 1
Study groups according to pre-procedural anticoagulation strategy. INR: International Normalised Ratio, OAC: oral anticoagulant, VKA: vitamin K antagonist. Full article ">Figure 2
Left atrium D-dimer levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. Dashed lines indicate diagnostic cut-off level for venous thromboembolic events (0.5 mg/L). PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. * p < 0.05, ** p < 0.01, *** p < 0.001. Statistical significance remained essentially the same when assessed after controlling for the effect of covariates associated with selection (age, sex) between treatment groups. Full article ">Figure 3
Left atrium plasmin-antiplasmin (PAP)-complex levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. * p < 0.05, ** p < 0.01. Statistical significance remained essentially the same when assessed after controlling for the effect of covariates associated with selection (age, sex) between treatment groups. Full article ">Figure 4
Left atrium α2- plasmin inhibitor activity levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. Dashed lines indicate lower and upper limit of reference interval (80–120%). PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. * p < 0.05, ** p < 0.01. Statistical significance remained essentially the same when assessed after controlling for the effect of covariates associated with selection (age, sex) between treatment groups. Full article ">Figure 5
Left atrium fibrinogen levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. Dashed lines indicate lower and upper limit of reference interval (1.5–4 g/L). PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. ** p < 0.01. Full article ">Figure 6
Left atrium fibrin monomer levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. Dashed lines indicate diagnostic cut-off level for prethrombotic conditions (10 mg/L). PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. * p < 0.05, ** p < 0.01, *** p < 0.001. Statistical significance remained essentially the same when assessed after controlling for the effect of covariates associated with selection (age, sex) between treatment groups. Full article ">Figure 7
Left atrium von Willebrand factor (VWF) antigen levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. Dashed lines indicate lower and upper limit of reference interval (50–160%). PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. ** p < 0.01, *** p < 0.001. Full article ">Figure 8
Left atrium FVIII activity levels before and after cryoballoon ablation procedure in AF patients on various pre-procedural anticoagulation strategies. Box and whisker plots indicate median, interquartile range, and total range. Dashed lines indicate lower and upper limit of reference interval (60–168%). PRE (empty bars): pre-ablation, POST (solid bars): post-ablation, OAC: oral anticoagulant, VKA: vitamin K antagonist. ** p < 0.01, *** p < 0.001. Full article ">

16 pages, 282 KiB

Open AccessReview

Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress

by Valentina Gambardella, Tania Fleitas, Noelia Tarazona, Federica Papaccio, Marisol Huerta, Susana Roselló, Francisco Gimeno-Valiente, Desamparados Roda and Andrés Cervantes

J. Clin. Med. 2020, 9(9), 3049; https://doi.org/10.3390/jcm9093049 - 22 Sep 2020

Cited by 20 | Viewed by 3146

Abstract

Gastroesophageal adenocarcinoma (GEA) represents a heterogeneous disease and, when diagnosed as locally advanced or metastatic, it is characterized by poor prognosis. During the last few years, several molecular classifications have been proposed to try to personalize treatment for those patients diagnosed with advanced [...] Read more.

Gastroesophageal adenocarcinoma (GEA) represents a heterogeneous disease and, when diagnosed as locally advanced or metastatic, it is characterized by poor prognosis. During the last few years, several molecular classifications have been proposed to try to personalize treatment for those patients diagnosed with advanced disease. Nevertheless, despite the great effort, precision medicine is still far from being a reality. The improvement in the molecular analysis due to the application of high throughput technologies based on DNA and RNA sequencing has opened a novel scenario leading to the personalization of treatment. The possibility to target epidermal growth factor receptor (HER)2, Claudine, Fibroblast Growth Factor Receptors (FGFR), and other alterations with a molecular matched therapy could significantly improve clinical outcomes over advanced gastric cancer patients. On the other hand, the development of immunotherapy could also represent a promising strategy in a selected population. In this review, we sought to describe the novel pathways implicated in GEA progression and the results of the molecular matched therapies. Full article

(This article belongs to the Special Issue Multimodality Treatments in Metastatic Gastric Cancer)

13 pages, 807 KiB

Open AccessArticle

Novel Sub-Clustering of Class III Skeletal Malocclusion Phenotypes in a Southern European Population Based on Proportional Measurements

by Leixuri de Frutos-Valle, Conchita Martín, José Antonio Alarcón, Juan Carlos Palma-Fernández, Ricardo Ortega and Alejandro Iglesias-Linares

J. Clin. Med. 2020, 9(9), 3048; https://doi.org/10.3390/jcm9093048 - 22 Sep 2020

Cited by 6 | Viewed by 2484

Abstract

Current phenotypic characterizations of Class III malocclusion are influenced more by gender or ethnic origin than by raw linear skeletal measurements. The aim of the present research is to develop a Class III skeletal malocclusion sub-phenotype characterization based on proportional cranial measurements using [...] Read more.

Current phenotypic characterizations of Class III malocclusion are influenced more by gender or ethnic origin than by raw linear skeletal measurements. The aim of the present research is to develop a Class III skeletal malocclusion sub-phenotype characterization based on proportional cranial measurements using principal component analysis and cluster analysis. Radiometric data from 212 adult subjects (115 women and 96 men) of southern European origin affected by Class III skeletal malocclusion were analyzed. A total of 120 measurements were made, 26 were proportional skeletal measurements, which were used to perform principal component analysis and subsequent cluster analysis. The remaining 94 supplementary measurements were used for a greater description of the identified clusters. Principal component analysis established eight principal components that explained 85.1% of the total variance. The first three principal components explained 51.4% of the variance and described mandibular proportions, anterior facial height proportions, and posterior–anterior cranial proportions. Cluster analysis established four phenotypic subgroups, representing 18.4% (C1), 20.75% (C2), 38.68% (C3), and 22.17% (C4) of the sample. A new sub-clustering of skeletal Class III malocclusions that avoids gender influence is provided. Our results improve clinicians’ resources for Class III malocclusion and could improve the diagnostic and treatment approaches for this malocclusion. Full article

(This article belongs to the Special Issue New Approaches and Technologies in Orthodontics)

► Show Figures

Figure 1

19 pages, 294 KiB

Open AccessReview

The Role of Thermal Water in Chronic Skin Diseases Management: A Review of the Literature

by Sara Cacciapuoti, Maria A. Luciano, Matteo Megna, Maria C. Annunziata, Maddalena Napolitano, Cataldo Patruno, Emanuele Scala, Roberta Colicchio, Chiara Pagliuca, Paola Salvatore and Gabriella Fabbrocini

J. Clin. Med. 2020, 9(9), 3047; https://doi.org/10.3390/jcm9093047 - 22 Sep 2020

Cited by 55 | Viewed by 11344

Abstract

The benefits of thermal water in different diseases have been known since ancient times. Over the past decades, a re-assessment of the use of mineral water for the treatment of several pathologic conditions has taken place around the world. Today, water therapy is [...] Read more.

The benefits of thermal water in different diseases have been known since ancient times. Over the past decades, a re-assessment of the use of mineral water for the treatment of several pathologic conditions has taken place around the world. Today, water therapy is being practiced in many countries that have a variety of mineral springs considerably different in their hydrogeologic origin, temperature, and chemical composition. Thermal water and balneotherapy offer several advantages: this approach needs no chemicals or potentially harmful drugs; there are almost no side effects during and after treatment, and there is a low risk to the patient’s general health and well-being. However, it is difficult to evaluate the efficacy of this therapeutic approach in clinical practice due to the complexity of molecular mechanisms underlying its efficacy. Here we review the current knowledge of the chemical, immunological, and microbiological basis for therapeutic effects of thermal water with a specific focus on chronic inflammatory skin diseases. We also describe recent evidence of the major dermatologic diseases that are frequently treated by balneotherapy with a remarkable rate of success. Moreover, we discuss the potential role of balneotherapy either alone or as a complement to conventional medical treatments. Full article

(This article belongs to the Special Issue Chronic Inflammatory Skin Diseases: An Update for Clinician)

15 pages, 1152 KiB

Open AccessArticle

Restless Legs Syndrome During Pregnancy and 12 Weeks Postpartum and Its Links to Cardiovascular Diseases, Stressful Life Events, and Psychiatric History

by Tamme W. Goecke, Patricia Schnakenberg, Markus Frensch and Natalia Chechko

J. Clin. Med. 2020, 9(9), 3046; https://doi.org/10.3390/jcm9093046 - 21 Sep 2020

Cited by 10 | Viewed by 3901

Abstract

Restless legs syndrome (RLS) is highly prevalent among pregnant women. In the present study, a neurological–obstetrical sample of 561 postpartum women was retrospectively screened for RLS symptoms during pregnancy and in the first 12 weeks postpartum. The first screening took place within 1 [...] Read more.

Restless legs syndrome (RLS) is highly prevalent among pregnant women. In the present study, a neurological–obstetrical sample of 561 postpartum women was retrospectively screened for RLS symptoms during pregnancy and in the first 12 weeks postpartum. The first screening took place within 1 to 6 days of delivery (T0) and the second 12 weeks after childbirth (T1). The pregnancy-related RLS prevalence rate was found to be 21% (n = 119), with the women suffering from RLS being more often affected by psychiatric history and having been more exposed to stressful life events. They were also found to have experienced baby blues more frequently shortly after childbirth. However, RLS in pregnancy did not appear to have any effect on the development of postpartum depression. Additionally, a positive trend was observed toward an association between pregnancy-related RLS and gestational diabetes and hypertension. Of the 119 women, 23 (19.3%) remained affected by RLS 12 weeks postpartum. Body mass index (BMI), weight gain, parity, childbearing history, or chronic stress exposure in pregnancy as measured by hair cortisol were not found to be linked to RLS. In summary, a comprehensive understanding of the interaction of clinical, environmental, and anamnestic factors can help shed valuable light on this pregnancy-related condition. Full article

(This article belongs to the Section Obstetrics & Gynecology)

► Show Figures

Figure 1

16 pages, 2820 KiB

Open AccessReview

Can Adenosine Fight COVID-19 Acute Respiratory Distress Syndrome?

by Carmela Falcone, Massimo Caracciolo, Pierpaolo Correale, Sebastiano Macheda, Eugenio Giuseppe Vadalà, Stefano La Scala, Marco Tescione, Roberta Danieli, Anna Ferrarelli, Maria Grazia Tarsitano, Lorenzo Romano and Antonino De Lorenzo

J. Clin. Med. 2020, 9(9), 3045; https://doi.org/10.3390/jcm9093045 - 21 Sep 2020

Cited by 21 | Viewed by 6135

Abstract

Coronavirus disease 2019 (COVID-19) patients can develop interstitial pneumonia, which, in turn, can evolve into acute respiratory distress syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has proteins capable of promoting the cytokine [...] Read more.

Coronavirus disease 2019 (COVID-19) patients can develop interstitial pneumonia, which, in turn, can evolve into acute respiratory distress syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has proteins capable of promoting the cytokine storm, especially in patients with comorbidities, including obesity. Since currently no resolutive therapy for ARDS has been found and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Through its receptors, adenosine is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier, and reduce the damage due to an overactivation of the immune system, such as that occurring in cytokine storms. These features are known in ischemia/reperfusion models and could also be exploited in acute lung injury with hypoxia. Considering these hypotheses, a COVID-19 patient with unresponsive respiratory failure was treated with adenosine for compassionate use. The results showed a rapid improvement of clinical conditions, with negativity of SARS-CoV2 detection. Full article

(This article belongs to the Special Issue COVID-19: Diagnostic Imaging and Beyond - Part I)

► Show Figures

Figure 1

22 pages, 1734 KiB

Open AccessReview

Bilateral Subthalamic Nucleus Deep Brain Stimulation under General Anesthesia: Literature Review and Single Center Experience

by Hye Ran Park, Yong Hoon Lim, Eun Jin Song, Jae Meen Lee, Kawngwoo Park, Kwang Hyon Park, Woong-Woo Lee, Han-Joon Kim, Beomseok Jeon and Sun Ha Paek

J. Clin. Med. 2020, 9(9), 3044; https://doi.org/10.3390/jcm9093044 - 21 Sep 2020

Cited by 11 | Viewed by 4305

Abstract

Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson’s disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative macrostimulation under local anesthesia (LA). However, many patients cannot tolerate the [...] Read more.

Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson’s disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative macrostimulation under local anesthesia (LA). However, many patients cannot tolerate the long operation time under LA without medication. In addition, it cannot be even be performed on PD patients with poor physical and neurological condition. Recently, it has been reported that STN DBS under general anesthesia (GA) can be successfully performed due to the feasible MER under GA, as well as the technical advancement in direct targeting and intraoperative imaging. The authors reviewed the previously published literature on STN DBS under GA using intraoperative imaging and MER, focused on discussing the technique, clinical outcome, and the complication, as well as introducing our single-center experience. Based on the reports of previously published studies and ours, GA did not interfere with the MER signal from STN. STN DBS under GA without intraoperative stimulation shows similar or better clinical outcome without any additional complication compared to STN DBS under LA. Long-term follow-up with a large number of the patients would be necessary to validate the safety and efficacy of STN DBS under GA. Full article

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

► Show Figures

Figure 1

Figure 1
Comparison of clinical outcomes between baseline and 6 months after STN Deep brain stimulation (DBS) under local anesthesia (LA) and general anesthesia (GA) each cohort. (A) Total Unified Parkinson’s Disease Rating Scale (UPDRS) and (B) UPDRS part III showed significant improvement after 6 months compared to baseline, except for LA cohort medication on state, there was no statistically significant difference between LA and GA cohort. (C) Hoehn & Yahr stage and (D) Schwab & England activities of daily living (ADL) showed no significant change in the medication on state in both LA and GA cohort, and no significant difference between two cohorts. (E) Dyskinesia disability and (F) Levodopa equivalent daily dose (LEDD) were significantly decreased in both LA and GA cohort. Only LEDD showed a significant difference in the change between LA and GA cohort. (G) Mini Mental State Examination (MMSE) and (H) Beck’s Depression Inventory (BDI), showed no statistically significant decrease in both LA and GA cohort. (I) Short form -36 (SF-36) physical health and (J) Short form -36 (SF-36) mental health showed no statistically significant increase in both LA and GA cohort. Full article ">Figure 2
Plotting of the electrode location based on the plotted position of the electrode in the axial view which is 3.5 mm below the anterior commissure (AC)–posterior commissure (PC) line in the human brain atlas of Schaltenbrand and Wahren. (A) Local anesthesia (LA) cohort, (B) General anesthesia (GA) cohort. Compared to LA cohort, the GA cohort showed a higher tendency for the electrode to be located within the subthalamic nucleus (STN). Full article ">

9 pages, 876 KiB

Open AccessArticle

Urgent Pericardiocentesis Is More Frequently Needed After Left Circumflex Coronary Artery Perforation

by Michał A. Surdacki, Marcin Major, Michał Chyrchel, Paweł Kleczyński, Tomasz Rakowski, Leszek Bryniarski, Marek Ujda, Renata Wysocka, Witold Żmuda, Andrzej Wiśniewski, Marcin Nosal, Maciej Maliszewski, Marcin Rzeszutko, Jacek Legutko, Andrzej Surdacki, Stanisław Bartuś and Łukasz Rzeszutko

J. Clin. Med. 2020, 9(9), 3043; https://doi.org/10.3390/jcm9093043 - 21 Sep 2020

Cited by 1 | Viewed by 2287

Abstract

Background: Coronary artery perforation (CAP) is a rare but potentially life-threatening complication of percutaneous coronary interventions (PCIs) due to the risk of cardiac tamponade. Strikingly, in contrast to numerous analyses of CAP predictors, only few studies were focused on the predictors of tamponade [...] Read more.

Background: Coronary artery perforation (CAP) is a rare but potentially life-threatening complication of percutaneous coronary interventions (PCIs) due to the risk of cardiac tamponade. Strikingly, in contrast to numerous analyses of CAP predictors, only few studies were focused on the predictors of tamponade after PCI, once iatrogenic CAP has occurred. Our aim was to search for clinical and periprocedural characteristics, including the coronary artery involved, associated with the development of acute cardiac tamponade among patients experiencing CAP. Methods: From the medical records of nine centers of invasive cardiology in southern Poland, we retrospectively selected 81 patients (80% with acute myocardial infarction) who had iatrogenic CAP with a visible extravasation jet during angiography (corresponding to type III CAP by the Ellis classification, CAP_III) over a 15-year period (2005–2019). Clinical, angiographic and periprocedural characteristics were compared between the patients who developed acute cardiac tamponade requiring urgent pericardiocentesis in the cathlab (n = 21) and those with CAP_III and without tamponade (n = 60). Results: CAP_III were situated in the left anterior descending artery (LAD) or its diagonal branches (51%, n = 41), right coronary artery (RCA) (24%, n = 19), left circumflex coronary artery (LCx) (16%, n = 13), its obtuse marginal branches (7%, n = 6) and left main coronary artery (2%, n = 2). Acute cardiac tamponade occurred in 24% (10 of 41), 21% (4 of 19) and 37% (7 of 19) patients who experienced CAP_III in the territory of LAD, RCA and LCx, respectively. There were no significant differences in the need for urgent pericardiocentesis (37%) in patients with CAP_III in LCx territory (i.e., the LCx or its obtuse marginal branches) compared to CAP_III in the remaining coronary arteries (23%) (p = 0.24). However, when CAP_III in the LCx were separated from CAP_III in obtuse marginal branches, urgent pericardiocentesis was more frequently performed in patients with CAP_III in the LCx (54%, 7 of 13) compared to subjects with CAP_III in an artery other than the LCx (21%, 14 of 68) (p = 0.03). The direction of this tendency remained consistent regardless of CAP management: prolonged balloon inflation only (n = 26, 67% vs. 13%, p = 0.08) or balloon inflation with subsequent stent implantation (n = 55, 50% vs. 24%, p = 0.13). Besides LCx involvement, no significant differences in other characteristics were observed between patients according to the need of urgent pericardiocentesis. Conclusions: CAP_III in the LCx appears to lead to a higher risk of acute cardiac tamponade compared to perforations involving other coronary arteries. This association may possibly be linked to distinct features of LCx anatomy and/or well-recognized delays in diagnosis and management of LCx-related acute coronary syndromes. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

11 pages, 1331 KiB

Open AccessArticle

Retrospective Analysis of a Modified Organizational Model to Guarantee CT Workflow during the COVID-19 Outbreak in the Tertiary Hospital of Padova, Italy

by Giacomo Cester, Chiara Giraudo, Francesco Causin, Deris Gianni Boemo, Mariagiulia Anglani, Alfio Capizzi, Giovanni Carretta, Annamaria Cattelan, Diego Cecchin, Vito Cianci, Andrea Crisanti, Giorgio De Conti, Daniele Donato, Luciano Flor, Joseph-Domenico Gabrieli, Marina Munari, Paolo Navalesi, Alberto Ponzoni, Maria Luisa Scapellato, Ivo Tiberio, Andrea Vianello and Roberto Stramare Show full author list Hide full author list

J. Clin. Med. 2020, 9(9), 3042; https://doi.org/10.3390/jcm9093042 - 21 Sep 2020

Cited by 4 | Viewed by 3111

Abstract

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) outbreak in Italy, the cluster of Vò Euganeo was managed by the University Hospital of Padova. The Department of Diagnostic Imaging (DDI) conceived an organizational approach based on three different pathways [...] Read more.

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) outbreak in Italy, the cluster of Vò Euganeo was managed by the University Hospital of Padova. The Department of Diagnostic Imaging (DDI) conceived an organizational approach based on three different pathways for low-risk, high-risk, and confirmed Coronavirus Disease 19 (COVID-19) patients to accomplish three main targets: guarantee a safe pathway for non-COVID-19 patients, ensure health personnel safety, and maintain an efficient workload. Thus, an additional pathway was created with the aid of a trailer-mounted Computed Tomography (CT) scanner devoted to positive patients. We evaluated the performance of our approach from February 21 through April 12 in terms of workload (e.g., number of CT examinations) and safety (COVID-19-positive healthcare workers). There was an average of 72.2 and 17.8 COVID-19 patients per day in wards and the Intensive Care Unit (ICU), respectively. A total of 176 high-risk and positive patients were examined. High Resolution Computed Tomography (HRCT) was one of the most common exams, and 24 pulmonary embolism scans were performed. No in-hospital transmission occurred in the DDI neither among patients nor among health personnel. The weekly number of in-patient CT examinations decreased by 27.4%, and the surgical procedures decreased by 29.5%. Patient screening and dedicated diagnostic pathways allowed the maintenance of high standards of care while working in safety. Full article

(This article belongs to the Special Issue COVID-19: Diagnostic Imaging and Beyond - Part I)

► Show Figures

Figure 1

Figure 1
Hospital workload during Phase 1 of Coronavirus Disease 19 (COVID-19) pandemic, showing mean volume per day and week from 21 February through 12 April 2020, death of first patient in Padova area, and identification of the Vò cluster. The reference timeline highlighting the regional and national steps of the pandemic is represented in (A). Graph (B) shows the daily number of COVID-19 patients admitted to the Intensive Care Unit (ICU) and devoted wards. Graph (C) shows the total daily number of CT (Computed Tomography) examinations performed on COVID-19 positive or suspected patients. Graph (D) shows the total weekly number of CT acquisitions for in-patients, Emergency Room (ER) and out-patients during Phase 1 of the outbreak from Monday 24 February, and graph (E) shows the total weekly number of surgical interventions for in-hospital patients in the same period. Green squares in graph (D) and (E) identify, as a reference, the mean value of the benchmark performance of CT and surgical activities observed in the four weeks before the outbreak. Both CT scans and surgical interventions for in-patients are shown in blue. Full article ">Figure 2
The flowchart represents the protocol applied in the Department of Diagnostic Imaging of the tertiary hospital of Padova to face the COVID-19 emergency. (a rented since the beginning of the pandemic; b very critical who could have not been transported to the truck were scanned in the closest CT scanner; then, the room was sanitized and locked according to the guidelines; c then, the CT room was locked and cleaned according to the guidelines. DDI = Department of Diagnostic Imaging). Full article ">Figure 3
Pie charts representing the units referring for Pathways B and C (high-risk and COVID-19-positive patients) who underwent CT examinations. Full article ">

18 pages, 329 KiB

Open AccessArticle

Risk Factors of Overweight and Obesity Related to Diet and Disordered Eating Attitudes in Adolescent Girls with Clinical Features of Polycystic Ovary Syndrome

by Małgorzata Mizgier, Grażyna Jarząbek-Bielecka, Justyna Opydo-Szymaczek, Natalia Wendland, Barbara Więckowska and Witold Kędzia

J. Clin. Med. 2020, 9(9), 3041; https://doi.org/10.3390/jcm9093041 - 21 Sep 2020

Cited by 23 | Viewed by 5717

Abstract

Background: We aimed to find the difference between girls with clinical features of Polycystic ovary syndrome (PCOS), divided into two groups: Overweight/obesity (Ov/Ob) and normal weight (N), related to diet, disordered eating attitudes (DEA), metabolic and hormonal differences, and to identify the risk [...] Read more.

Background: We aimed to find the difference between girls with clinical features of Polycystic ovary syndrome (PCOS), divided into two groups: Overweight/obesity (Ov/Ob) and normal weight (N), related to diet, disordered eating attitudes (DEA), metabolic and hormonal differences, and to identify the risk factors of being overweight or obese. Methods: Seventy-eight adolescents with PCOS, aged 14–18 years, were divided into Ov/Ob and N groups. Patients underwent blood tests for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, DHEA-S, estradiol, of sex hormone-binding globulin (SHBG), fasting glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and lipid profile. Nutrition was evaluated using a 3-day food record. To examine the level of DEA, the Eating Attitudes Test-26 (EAT-26) was used. We defined an EAT-26 score ≥20 as positive for DEA. Logistic regression was carried out to identify the independent predictors of being overweight and obese. Results: An increase of 10 g in plant protein intake decreased the probability of being overweight and of obesity (OR = 0.54; p = 0.036). EAT-26 score ≥20 was correlated with a 7-fold (OR = 6.88; p = 0.02) increased odds of being overweight or of obesity. Conclusion: Being overweight and obesity in adolescents with PCOS may be associated with DEA and the type and amount of protein intake. Full article

(This article belongs to the Section Mental Health)

11 pages, 1035 KiB

Open AccessArticle

Utility of Magnetic Resonance Imaging for Differentiating Necrotizing Fasciitis from Severe Cellulitis: A Magnetic Resonance Indicator for Necrotizing Fasciitis (MRINEC) Algorithm

by Min-Chul Kim, Sujin Kim, Eun Been Cho, Guen Young Lee, Seong-Ho Choi, Seon Ok Kim and Jin-Won Chung

J. Clin. Med. 2020, 9(9), 3040; https://doi.org/10.3390/jcm9093040 - 21 Sep 2020

Cited by 16 | Viewed by 7848

Abstract

We developed a new magnetic resonance indicator for necrotizing fasciitis (MRINEC) algorithm for differentiating necrotizing fasciitis (NF) from severe cellulitis (SC). All adults with suspected NF between 2010 and 2018 in a tertiary hospital in South Korea were enrolled. Sixty-one patients were diagnosed [...] Read more.

We developed a new magnetic resonance indicator for necrotizing fasciitis (MRINEC) algorithm for differentiating necrotizing fasciitis (NF) from severe cellulitis (SC). All adults with suspected NF between 2010 and 2018 in a tertiary hospital in South Korea were enrolled. Sixty-one patients were diagnosed with NF and 28 with SC. Among them, 34 with NF and 15 with SC underwent magnetic resonance imaging (MRI). The MRINEC algorithm, a two-step decision tree including T2 hyperintensity of intermuscular deep fascia and diffuse T2 hyperintensity of deep peripheral fascia, diagnosed NF with 94% sensitivity (95% confidence interval (CI), 80–99%) and 60% specificity (95% CI, 32–84%). The algorithm accurately diagnosed all 15 NF patients with a high (≥8) laboratory risk indicator for necrotizing fasciitis (LRINEC) score. Among the five patients with an intermediate (6–7) LRINEC score, sensitivity and specificity were 100% (95% CI, 78–100%) and 0% (95% CI, 0–84%), respectively. Finally, among the 29 patients with a low (≤5) LRINEC score, the algorithm had a sensitivity and specificity of 88% (95% CI, 62–98%) and 69% (95% CI, 39–91%), respectively. The MRINEC algorithm may be a useful adjuvant method for diagnosing NF, especially when NF is suspected in patients with a low LRINEC score. Full article

(This article belongs to the Section Orthopedics)

► Show Figures

Figure 1

16 pages, 473 KiB

Open AccessReview

Risk Assessment Using Risk Scores in Patients with Acute Coronary Syndrome

by Dean Chan Pin Yin, Jaouad Azzahhafi and Stefan James

J. Clin. Med. 2020, 9(9), 3039; https://doi.org/10.3390/jcm9093039 - 21 Sep 2020

Cited by 24 | Viewed by 6719

Abstract

Risk scores are widely used in patients with acute coronary syndrome (ACS) prior to treatment decision-making at different points in time. At initial hospital presentation, risk scores are used to assess the risk for developing major adverse cardiac events (MACE) and can guide [...] Read more.

Risk scores are widely used in patients with acute coronary syndrome (ACS) prior to treatment decision-making at different points in time. At initial hospital presentation, risk scores are used to assess the risk for developing major adverse cardiac events (MACE) and can guide clinicians in either discharging the patients at low risk or swiftly admitting and treating the patients at high risk for MACE. During hospital admission, risk assessment is performed to estimate mortality, residual ischemic and bleeding risk to guide further in-hospital management (e.g., timing of coronary angiography) and post-discharge management (e.g., duration of dual antiplatelet therapy). In the months and years following ACS, long term risk can also be assessed to evaluate current treatment strategies (e.g., intensify or reduce pharmaceutical treatment options). As multiple risk scores have been developed over the last decades, this review summarizes the most relevant risk scores used in ACS patients. Full article

(This article belongs to the Special Issue Antithrombotic Treatment of Acute Coronary Syndrome)

► Show Figures

Figure 1

26 pages, 3772 KiB

Open AccessReview

Impact of Exercise on Immunometabolism in Multiple Sclerosis

by Remsha Afzal, Jennifer K Dowling and Claire E McCoy

J. Clin. Med. 2020, 9(9), 3038; https://doi.org/10.3390/jcm9093038 - 21 Sep 2020

Cited by 20 | Viewed by 7752

Abstract

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most [...] Read more.

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS. Full article

(This article belongs to the Special Issue Exercise and Multiple Sclerosis)

► Show Figures

Figure 1

Figure 1
An outline of MS immunopathology: MS results from breakdown of the blood-brain barrier (BBB) leading to migration of immune cells into the central nervous system (CNS). These immune cells secrete a range of pro-inflammatory cytokines as well as reactive oxygen and nitrogen species (ROS/RNS), which induce inflammation, formation of sclerotic plaques (lesions), demyelination and axonal degradation. Pathological immune cells in MS include innate immune cells like activated macrophages and resident microglia, autoreactive T-cells (that are activated at peripheral sites, potentially through molecular mimicry, bystander activation or the co-expression of T-cell receptors (TCRs) with different specificities [<a href="#B2-jcm-09-03038" class="html-bibr">2</a>]) and antibody producing B-cells. (APC: Antigen-presenting cell); Image made in BiorenderTM (BioRender.com). Full article ">Figure 2
An outline of key metabolic pathways altered upon immune cell activation: Cells modify specific metabolic pathways depending on their requirements for activation, growth, development or survival. This capability to shift utilisation of various pathways to generate energy from nutrients like carbohydrates (e.g., glucose), proteins and fats is termed immunometabolism. ATP: Adenosine Triphosphate; LDH: Lactate Dehydrogenase; MCT: Monocarboxylate Transporter; HK: Hexokinase; G-6P: Glucose-6-Phosphate; PGI: Phosphoglucoisomerase; F-6P: Fructose-6-phosphate; PFK1: Phosphofructokinase 1; F-1,6 BP: Fructose 1,6-Bisphosphate; ALDA Aldolase; G-3P: Glyceraldehyde-3-phosphate; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; 1,3 BPG: 1,3-bisphosphoglycerate; PEP: Phosphoenolpyruvate; PK: Pyruvate Kinase; G6PD: Glucose-6-phosphate dehydrogenase; R5BP: Ribulose 1,5-bisphosphate; NADPH: Nicotinamide adenine dinucleotide phosphate; Acetyl CoA: Acetyl coenzyme A; ACLY: ATP citrate lyase; ACC: Acetyl-CoA carboxylase; FAS: Fatty acid synthase; HMGACR: HMG-CoA reductase; IDH: Isocitrate dehydrogenase; SDH: Succinate dehydrogenase; FH: Fumarase; MDH: Malate dehydrogenase; OAA: Oxaloacetate; CS: Citrate Synthase; ACS: Acetyl CoA Synthase; FAO: Fatty Acid Oxidation; CPT: Carnitine palmitoyltransferase; GLUD: Glutamate dehydrogenase; GLS: Glutaminase, NADH: Nicotinamide adenine dinucleotide; FADH2: Flavin adenine dinucleotide, CoQ: Coenzyme Q; Cyt C: Cytochrome C; TCA: Tricarboxylic Acid Cycle. Image made in BiorenderTM. Full article ">Figure 3
A summary of the impact glycolysis has on cells in MS: Glycolysis is a major pathway via which glucose is metabolised and generally is involved in activation of various immune cell subsets that are pathological in MS. Activation of immune cells such as in monocytes, macrophages and CD8+ T cells, and differentiation of CD4+ T-cell subsets, such as TH1 and TH17, leads to production of pro-inflammatory cytokines and cytotoxic granules. IL: Interleukin; TNF: Tumor Necrosis Factor; IFN: Interferon; TH: T Helper Cell; TP1: Topoisomerase 1; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; MS: Multiple Sclerosis. Image made in BiorenderTM. Full article ">Figure 4
Fatty Acid metabolism in immune cell subtypes: Fatty acid oxidation (FAO) is primarily utilised by immunoregulatory cell types such as anti-inflammatory M2-like macrophages and Treg cells to boost oxidative respiration by their mitochondria, whereas synthesis of fatty acids and cholesterol is increased in effector T-cells and B-cells for differentiation and development as well as in M1-like proinflammatory macrophages. Image made in BiorenderTM. Full article ">Figure 5
Mitochondrial metabolism in determining macrophage phenotype: Inflammatory macrophages constitute one of the largest immune cell infiltrates in CNS in MS. Proinflammatory macrophages have a distinct metabolic profile where they have reduced ATP production via OxPhos, altered TCA cycle metabolites (such as enhanced citrate and succinate levels), and have upregulated glycolysis and fatty acid synthesis pathways via mammalian target of Rapamycin (mTOR) activation. Such dysregulated mitochondrial metabolism allows these cells to be highly bactericidal by secreting inflammatory cytokines and ROS. On the other hands, immunoregulatory macrophages rely predominantly on TCA cycle and electron transport chain mediated OxPhos to generate ATP. This is aided by increased FAO via 5’ AMP-activated protein kinase (AMPK) activation. Image adapted from BiorenderTM. Full article ">Figure 6
Impact of exercise on immune-inflammatory response and metabolic function. Regular aerobic/endurance exercise has shown to induce a tolerogenic glucose state, which is associated with a state of immunomodulation through changes in amino acid metabolism (e.g., increased kyunrenic acid and glutamate oxidation) and nutrient sensor pathways (increased AMPK:mTOR ratio). This induces increases mitochondrial biogenesis and oxidative respiration at the mitochondria at least partly through increased fatty acid oxidation (FAO) and decreased fatty acid synthesis (FAS). This impacts on various organs and cells, including (1) higher myokine IL-6 secretion by skeletal muscle tissue; (2) Decreased proinflammatory macrophage and effector T cell number and cytotoxic activity; (3) Decreased ROS and proinflammatory cytokine production by innate immune cells, as well as an increased antioxidant response; (4) increase in Treg number and function; (5) decrease in leptin secretion (likely due to reduced fat mass) and increase in adiponectin secretion, and lower proinflammatory M1-like macrophage infiltration. Image made in BiorenderTM. Full article ">

13 pages, 468 KiB

Open AccessArticle

Monocyte Chemoattractant Protein-1 Is an Independent Predictor of Coronary Artery Ectasia in Patients with Acute Coronary Syndrome

by Juan Antonio Franco-Peláez, Roberto Martín-Reyes, Ana María Pello-Lázaro, Álvaro Aceña, Óscar Lorenzo, José Luis Martín-Ventura, Luis Blanco-Colio, María Luisa González-Casaus, Ignacio Hernández-González, Rocío Carda, María Luisa Martín-Mariscal, Jesús Egido and José Tuñón

J. Clin. Med. 2020, 9(9), 3037; https://doi.org/10.3390/jcm9093037 - 21 Sep 2020

Cited by 8 | Viewed by 2592

Abstract

Our purpose was to assess a possible association of inflammatory, lipid and mineral metabolism biomarkers with coronary artery ectasia (CAE) and to determine a possible association of this with acute atherotrombotic events (AAT). We studied 270 patients who underwent coronary angiography during an [...] Read more.

Our purpose was to assess a possible association of inflammatory, lipid and mineral metabolism biomarkers with coronary artery ectasia (CAE) and to determine a possible association of this with acute atherotrombotic events (AAT). We studied 270 patients who underwent coronary angiography during an acute coronary syndrome 6 months before. Plasma levels of several biomarkers were assessed, and patients were followed during a median of 5.35 (3.88–6.65) years. Two interventional cardiologists reviewed the coronary angiograms, diagnosing CAE according to previously published criteria in 23 patients (8.5%). Multivariate binary logistic regression analysis was used to search for independent predictors of CAE. Multivariate analysis revealed that, aside from gender and a diagnosis of dyslipidemia, only monocyte chemoattractant protein-1 (MCP-1) (OR = 2.25, 95%CI = (1.35–3.76) for each increase of 100 pg/mL, p = 0.001) was independent predictor of CAE, whereas mineral metabolism markers or proprotein convertase subtilisin/kexin type 9 were not. Moreover, CAE was a strong predictor of AAT during follow-up after adjustment for other clinically relevant variables (HR = 2.67, 95%CI = (1.22–5.82), p = 0.013). This is the first report showing that MCP-1 is an independent predictor of CAE, suggesting that CAE and coronary artery disease may share pathogenic mechanisms. Furthermore, CAE was associated with an increased incidence of AAT. Full article

(This article belongs to the Special Issue Atherosclerosis: Endothelial Dysfunction and Beyond)

► Show Figures

Figure 1

15 pages, 4173 KiB

Open AccessArticle

Pilot Study on the Use of a Laser-Structured Double Diamond Electrode (DDE) for Biofilm Removal from Dental Implant Surfaces

by Maximilian Koch, Andreas Burkovski, Manuel Zulla, Stefan Rosiwal, Walter Geißdörfer, Roman Dittmar and Tanja Grobecker-Karl

J. Clin. Med. 2020, 9(9), 3036; https://doi.org/10.3390/jcm9093036 - 21 Sep 2020

Cited by 10 | Viewed by 3682

Abstract

No proper treatment option for peri-implantitis exists yet. Based on previous studies showing the in vitro effectiveness of electrochemical disinfection using boron-doped diamond electrodes, novel double diamond electrodes (DDE) were tested here. Using a ceramic carrier and a laser structuring process, a clinically [...] Read more.

No proper treatment option for peri-implantitis exists yet. Based on previous studies showing the in vitro effectiveness of electrochemical disinfection using boron-doped diamond electrodes, novel double diamond electrodes (DDE) were tested here. Using a ceramic carrier and a laser structuring process, a clinically applicable electrode array was manufactured. Roughened metal discs (n = 24) made from Ti-Zr alloy were exposed to the oral cavities of six volunteers for 24 h in order to generate biofilm. Then, biofilm removal was carried out either using plastic curettes and chlorhexidine digluconate or electrochemical disinfection. In addition, dental implants were contaminated with ex vivo multispecies biofilm and disinfected using DDE treatment. Bacterial growth and the formation of biofilm polymer were determined as outcome measures. Chemo-mechanical treatment could not eliminate bacteria from roughened surfaces, while in most cases, a massive reduction of bacteria and biofilm polymer was observed following DDE treatment. Electrochemical disinfection was charge- and time-dependent and could also not reach complete disinfection in all instances. Implant threads had no negative effect on DDE treatment. Bacteria exhibit varying resistance to electrochemical disinfection with Bacillus subtilis, Neisseria sp., Rothiamucilaginosa, Staphylococcus haemolyticus, and Streptococcus mitis surviving 5 min of DDE application at 6 V. Electrochemical disinfection is promising but requires further optimization with respect to charge quantity and application time in order to achieve disinfection without harming host tissue. Full article

(This article belongs to the Special Issue Experimental Dental Research—New Concepts for Future Patient Needs)

► Show Figures

Figure 1

Figure 1
Maxillary splint with recesses for mounting Ti-Zr discs. (a) Recess used for mounting the Ti-Zr discs allowing for easy removal, (b) intraoral situation with splint in place. Full article ">Figure 2
Ceramic double diamond electrode. The conductive boron-doped diamond (BDD) layer is added to a non-conductive carrier. The laser cut allows both electrodes to share the same carrier and reduces the gap between the anode and cathode. (a) Schematic representation, (b) prototype. Full article ">Figure 3
Chemo-mechanical debridement of Ti-Zr discs following biofilm formation. (a) Harvesting of the disc from the splint, (b) treatment with plastic curette, (c) rinsing with chlorhexidine, (d) samples repeatedly pressed with roughened and smooth surface on blood agar plate. Full article ">Figure 4
Experimental setup for electrochemical disinfection. (a) Schematic presentation, (b) situation during disinfection process with Ti-Zr disc resting on PE-UHMW net. Please note the gas bubbles indicating the electrochemical reaction. Full article ">Figure 5
Crystal violet stained biofilm at the disc’s surface. (a) Roughened surface completely covered but also (b) mild and (c) strong biofilm formation at the smoother surface was observed. Full article ">Figure 6
Images of blood agar plates into which the Ti-Zr discs had been repeatedly pressed. The plates have been incubated for 24 h at 37 °C. Full article ">Figure 7
Quantitative analysis of biofilm formation at the Ti-Zr disc surface at different stages. Black: Control/no treatment/positive, white: curette/chlorhexidine, dark gray: 2.5 min DDE treatment, gray: 5 min DDE treatment, *: biofilm detached during washing step. Full article ">Figure 8
Standardized photographs of blood agar plates onto which the implants had been rolled. The plates have been incubated for 24 h at 37 °C. No bacterial growth was observed after DDE treatment at 9 V/Ø 105 mA. Full article ">

22 pages, 2137 KiB

Open AccessArticle

CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis

by Monika Abramiuk, Ewelina Grywalska, Izabela Korona-Głowniak, Paulina Niedźwiedzka-Rystwej, Grzegorz Polak, Jan Kotarski and Jacek Roliński

J. Clin. Med. 2020, 9(9), 3035; https://doi.org/10.3390/jcm9093035 - 21 Sep 2020

Cited by 8 | Viewed by 3331

Abstract

The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we [...] Read more.

The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we investigated the expression of CD200 and CD200R on T and B lymphocytes and the serum level of soluble CD200 (sCD200) using flow cytometry and ELISA, respectively. Peripheral blood samples were collected from 54 female patients and 20 healthy, age-matched controls. Results were tested for correlation with disease severity and selected clinical parameters. We demonstrated that the differences in sCD200 levels (p = 0.001), the frequencies of CD200-positive T and B lymphocytes (p < 0.001 and p = 0.004, respectively), and the frequencies of CD200R-positive T and B lymphocytes (p < 0.001 for all comparisons) in the study group correlated positively with disease severity. Receiver operating characteristic (ROC) analysis indicated that aberrant expression of CD200/CD200R might serve as a marker to distinguish between EMS cases. Finally, negative co-stimulatory factors may contribute to the induction and persistence of inflammation associated with EMS. It seems that it is essential to determine whether alteration in the CD200/CD200R pathway can be therapeutically targeted in EMS. Full article

(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)

► Show Figures

Figure 1

Figure 1
Correlations between the expression of CD200 and CD200R and selected laboratory parameters in patients with the EMS. Spearman correlation coefficients: (A) Correlation between the frequencies of CD19+/CD200+ B lymphocytes and CD3+/CD16+/CD56+ NK cells (Pearson’s correlation coefficient; R = −0.33, p = 0.013); (B) correlation between the frequencies of CD8+/CD200R+ T lymphocytes and CD3+/CD16+/CD56+ NK cells (R = −0.36, p = 0.007). Full article ">Figure 2
Receiver operating characteristic (ROC) curve analysis showing the sensitivity and specificity of CD200 expression in EMS patients for CD4+/CD8+/CD200+ T lymphocyte frequencies (%) and CD19+/CD200 B lymphocyte frequencies (%). Full article ">Figure 3
Receiver operating characteristic (ROC) curve analysis showing the sensitivity and specificity of CD200R expression in EMS patients for CD4+/CD8+/CD200R+ T lymphocyte frequencies (%) and CD19+/CD200R lymphocyte frequencies (%). Full article ">Figure A1
Sample analysis of CD4+/CD8+/CD200 T lymphocytes and CD19+/CD200 B lymphocytes in EMS patients. Full article ">Figure A2
Sample analysis of CD4+/CD8+/CD200R T lymphocytes and CD19+/CD200R B lymphocytes in EMS patients. Full article ">

10 pages, 456 KiB

Open AccessArticle

Clinical Course of Pseudophakic Cystoid Macular Edema Treated with Nepafenac

by Alexander Aaronson, Asaf Achiron and Raimo Tuuminen

J. Clin. Med. 2020, 9(9), 3034; https://doi.org/10.3390/jcm9093034 - 21 Sep 2020

Cited by 9 | Viewed by 3798

Abstract

Background: To evaluate the clinical course of pseudophakic cystoid macular edema (PCME) treated with topical non-steroidal anti-inflammatory drugs (NSAIDs). Methods: An analysis of the clinical course of PCME consisting of 536 eyes of 536 patients from five consecutive randomized clinical trials aimed at [...] Read more.

Background: To evaluate the clinical course of pseudophakic cystoid macular edema (PCME) treated with topical non-steroidal anti-inflammatory drugs (NSAIDs). Methods: An analysis of the clinical course of PCME consisting of 536 eyes of 536 patients from five consecutive randomized clinical trials aimed at the optimization of anti-inflammatory medication in patients undergoing routine cataract surgery. PCME was classified as (i) grade 0a; no macular thickening, (ii) grade 0b; macular thickening (central subfield macular thickness (CSMT) increase of at least 10%) without signs of macular edema, (iii) grade I; subclinical PCME, (iv) grade II; acute PCME, (v) grade III; long-standing PCME. Eyes with PCME classification from grade I onwards were treated with nepafenac 1 mg/mL t.i.d. for two months. Results: CSMT increase of at least 10% at any postoperative timepoint with cystoid changes—a criterion for PCME—was found in 19 of 536 eyes (total incidence 3.5%). Of these 19 eyes, 13 eyes (total incidence 2.4%) had clinically significant PCME. PCME was considered clinically significant when both of the following visual acuity criteria were fulfilled. At any timepoint after the cataract surgery both the corrected distance visual acuity (CDVA) gain was less than 0.4 decimals from that of preoperative CDVA, and the absolute CDVA level remained below 0.8 decimals. Only one of the 19 eyes with criteria for PCME (total incidence 0.2%, incidence of PCME eyes 5.3%) showed no macular edema resolution within 2 months after topical nepafenac administration. Conclusions: PCME in most cases is self-limiting using topical nepafenac without any further need for intravitreal treatment. Full article

(This article belongs to the Special Issue Cataract Surgery and Postoperative Care)

► Show Figures

Figure 1

11 pages, 510 KiB

Open AccessArticle

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis

by Giulia Dei, Paola Rebora, Martina Catalano, Marco Sebastiani, Paola Faverio, Maria Rosa Pozzi, Andreina Manfredi, Paolo Cameli, Francesco Salton, Carlo Salvarani, Lorenzo Cavagna, Marco Confalonieri, Elena Bargagli, Fabrizio Luppi and Alberto Pesci

J. Clin. Med. 2020, 9(9), 3033; https://doi.org/10.3390/jcm9093033 - 21 Sep 2020

Cited by 6 | Viewed by 2816

Abstract

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with [...] Read more.

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, “real life” study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline. Full article

(This article belongs to the Special Issue Diagnosis, Clinical Features and Management of Interstitial Lung Diseases in Rheumatic Disorders)

► Show Figures

Figure 1

22 pages, 2918 KiB

Open AccessArticle

Computational Analysis of Clinical and Molecular Markers and New Theranostic Possibilities in Primary Open-Angle Glaucoma

by María D. Pinazo-Durán, José J. García-Medina, José M. Bolarín, Silvia M. Sanz-González, Mar Valero-Vello, Javier Abellán-Abenza, Vicente Zanón-Moreno and Javier Moreno-Montañés

J. Clin. Med. 2020, 9(9), 3032; https://doi.org/10.3390/jcm9093032 - 21 Sep 2020

Cited by 4 | Viewed by 2892

Abstract

Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) [...] Read more.

Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) and experimental tests (enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and Western blot/immunoblotting) directed to evaluate the oxidative stress, inflammation, apoptosis, and neurodegeneration processes, we gather information to build a network of data to perform a computational bioinformatics analysis. Our results showed strong interaction of the above players and its downstream effectors in POAG pathogenesis. In conclusion, specific risk factors were identified, and molecules involved in multiple pathways were found in relation to anterior and posterior eye segment glaucoma changes, pointing to new theranostic challenges for better managing POAG progression. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

► Show Figures

Figure 1

Figure 1
Ophthalmological evaluation of the study participants. (A,B) show the best corrected visual acuity (BCVA) (expressed in decimals; see the LogMAR correspondence in the text) in the right and left eyes. (C,D) indicate the IOP values (mmHg) in both eyes. In the (E,F), the CCT (in µm) from each eye was reflected. (G,H) display the C/D ratio in the eyes of the study participants. (I,J) show the RNFL thickness observed in the OCT examination from the participants eyes. Finally the (K,L) reflect the MD values obtained from the VF performance in both eyes. CG: control group; POAG: primary open-angle glaucoma; RE: right eye, LE: left eye; BCVA: best corrected visual acuity, IOP: intraocular pressure; CCT: central corneal thickness; C/D ratio: cup to disc ratio; RNFL: retinal nerve fiber layer; OCT: optic coherence tomography; MD: mean deviation; VF: visual field. Full article ">Figure 2
Oxidative stress markers in aqueous humor and plasma samples from the study participants. The OS overtime results in structural and functional eye damage. (A) Significantly higher MDA/TBARS expression levels (mol/L) in the aqueous humor from the POAG vs. the CG. (B) Significantly lower values of the TAC (nmol/L) in the aqueous humor from the POAG biosamples respect to those from the CG. (C) SOD expression shows significantly higher levels (UL) in the POAG aqueous humor as compared to the counterparts. (D) Significantly higher GPx levels were seen in the POAG aqueous humor vs. the CG. (E) Plasma vit C concentration (µg/mL) was significantly lower in the POAG vs. CG. (F) Aqueous humor NO levels (µmol/L) were significantly higher in the POAG patients respect to the healthy control participants. CG: control group (cataract subjects for aqueous humor comparative studies); POAG: primary open-angle glaucoma; MDA/TBARS: malondialdehyde/thiobarbituric acid reactive substances; TAC: total antioxidant capacity; SOD: superoxide dismutase; GPx: Glutathione peroxidase; NO: nitric oxide. p < 0.05 for all parameters in this figure. Full article ">Figure 3
Cytokine expression in tears, aqueous humor, and plasma of glaucoma patients vs. the healthy controls. Differential expression profile of the IL-1β (A), IL-2 (B), IL-4 (C), IL-5 (D), IL-6 (E), IL-8 (F), and IL-10 (G) (as expressed in pg/mL). It is observed a statistically significant increase of the chemokine IL-8 as it can be seen in the (G), between the POAG vs. the CG tear samples. CG: control group; POAG: primary open-angle glaucoma; IL: interleukin. Full article ">Figure 4
Set of inflammatory mediators TNFα (A), INF-g (B), GM CSF (C) and VEGF (D) as determined in biological samples of the study participants (expressed in pg/mL). Only the tear expression of TNFα, as reflected in the (B) was significantly different between the two study groups (p < 0.05). CG: control group; POAG: primary open-angle glaucoma; TNFα: tumor necrosis factorα; INFγ: interferonγ; GM-CSF: granulocyte-macrophage colony stimulating factor; VEGF: vascular endothelial growth factor. Full article ">Figure 5
Differential expression profile (relative densitometric units) in the aqueous humor from the glaucoma vs. the control participants. The CASP3 (A) and PARP-1 (B) were significantly higher in the POAG vs. the CG. Comparison of the expression profile of the PARP-1 85 kD and 24 kD fragments between the aqueous humor from the POAG and the the CG are reflected in (C) and (D). CASP3: caspase 3; CG: control group (cataract subjects forming the comparative group); POAG: primary open-angle glaucoma; RDU: relative densitometric units (laser densitometry); PARP-1: poly (ADP-ribose) polymerase. Full article ">Figure 6
Neuroprotectants and neurotransmitters in the study participants. (A,B) Plasma serotonin and dopamine expression (ng/mL) was significantly lower in samples of the POAG patients than in the CG. (C) Brain Derived Neurotrophic Factor (BDNF) aqueous humor expression (pg/mL) was significantly lower in the POAG vs. the CG. CG: control group (cataract subjects as comparative group); POAG: primary open-angle glaucoma; BDNF: brain-derived neurotrophic factor. p < 0.05 for all parameters. Full article ">Figure 7
New diagnostic players and potential new therapies as primary-open-angle glaucoma theranostics. Excessive ROS generation/accumulation (superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH)) selectively damage the lipids, proteins, and nucleic acids. MDA is an important lipid peroxidation byproduct. Elevated levels of pro-oxidants and decreased antioxidant activity spreads the oxidative injury. OS can induce activation of transcription factors, leading to gene expression involved in inflammation. In fact, OS stress activates the iNOS, a pivotal element of the transcription factor NF-kB pathway that controls the pro-inflammatory response by releasing among others the TNFα and IL-8, both significantly augmented in POAG. Serotonin and dopamine are really prone to autooxidation, and its toxic metabolites may contribute to increase neurodegeneration. Lower plasma levels of these neurotransmitters have been found in POAG. Glaucoma neurodegeneration is the result of the apoptotic death of the RGC. Lower levels of BDNF have also been identified in our POAG biosamples. ROS: reactive oxygen species; MDA: malondialdehyde; OS: oxidative stress; iNOS: inducible nitric oxide synthase; NF-κB: nuclear factor kappa B; TNFα: tumor necrosis factor alpha; IL-8: interleukin 8; RGC: retinal ganglion cells; BDNF: brain-derived neurotrophic factor. Full article ">

13 pages, 5475 KiB

Open AccessArticle

Revision Arthroplasty Through the Direct Anterior Approach Using an Asymmetric Acetabular Component

by Peter Michael Prodinger, Igor Lazic, Konstantin Horas, Rainer Burgkart, Rüdiger von Eisenhart-Rothe, Manuel Weissenberger, Maximilian Rudert and Boris Michael Holzapfel

J. Clin. Med. 2020, 9(9), 3031; https://doi.org/10.3390/jcm9093031 - 21 Sep 2020

Cited by 8 | Viewed by 3347

Abstract

Despite increasing numbers of primary hip arthroplasties performed through the direct anterior approach (DAA), there is a lack of literature on DAA revision arthroplasty. The present study was performed in order to evaluate outcomes and revision rates after revision through the DAA using [...] Read more.

Despite increasing numbers of primary hip arthroplasties performed through the direct anterior approach (DAA), there is a lack of literature on DAA revision arthroplasty. The present study was performed in order to evaluate outcomes and revision rates after revision through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation. In a retrospective cohort study, we analyzed prospectively collected data of 57 patients (61 hips, 43 female, 18 male) who underwent aseptic acetabular component revision through the DAA with the abovementioned implant system between January 2015 and December 2017. The mean follow-up was 40 months (12–56). Survival rates were estimated using the Kaplan–Meier method. All complications were documented and functional outcomes were assessed pre- and postoperatively. Kaplan–Meier analysis revealed an estimated five-year implant survival of 97% (confidence interval CI 87–99%). The estimated five-year survival with revision for any cause was 93% (CI 83–98%). The overall revision rate was 6.6% (n = 4). Two patients had to undergo revision due to periprosthetic infection (3.3%). In one patient, the acetabular component was revised due to aseptic loosening four months postoperatively. Another patient suffered from postoperative iliopsoas impingement and was treated successfully by arthroscopic iliopsoas tenotomy. Two (3.3%) of the revised hips dislocated postoperatively. The mean Harris Hip Score improved from 35 (2–66) preoperatively to 86 (38–100) postoperatively (p < 0.001). The hip joint’s anatomical center of rotation was restored at a high degree of accuracy. Our findings demonstrate that acetabular revision arthroplasty through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation is safe and practicable, resulting in good radiographic and clinical midterm results. Full article

(This article belongs to the Special Issue The 4 R’s of Modern Adult Hip Surgery: From Regeneration and Reconstruction to Replacement and Revision)

► Show Figures

Figure 1

Figure 1
(A) A 72-year-old female patient presenting with significant polyethylene wear and aseptic loosening of the acetabular component which was implanted 11 years ago (antero-posterior and axial views). The intraoperative bone defect evaluation revealed a cranial and lateral segmental defect with supportive dome and acetabular rim (Paprosky type IIB). (B) Radiographic imaging 12 months postoperatively (a.p. and axial views) demonstrate a well-fixed asymmetric acetabular component filling the cranial defect. The distal positioning of the insert makes it possible to reconstruct the anatomical center of rotation and to treat any pre-existing leg-length discrepancy (HHS: 56 preoperatively, 91 postoperatively; operation time OT 72 min). Full article ">Figure 2
(A) A 63-year-old female patient with failure of the acetabular implant and subsequent cranial migration 18 years after the index procedure (a.p. and axial views). Intraoperative defect evaluation revealed a large uncontained cranio-lateral defect (“up-and-out”) with rim destruction of more than 30% (Paprosky type IIIA defect). (B) Radiographs 24 months postoperatively revealed a stable acetabular implant augmented with multiple screws through the implant’s body and the iliac flange (HHS: 25 preoperatively, 81 postoperatively; OT 79 min). Full article ">Figure 3
(A) A.p. and axial radiographs of an 81-year-old female patient with large periacetabular osteolyses due to wear debris 17 years after primary hip arthroplasty. (B) Multiaxial CT analyses revealed insufficient stability of both the anterior and posterior column. Intraoperatively, the large iliac defect was contained by an egg shell-like outer cortex. More than 60% of the acetabular rim was deficient. The iliac defect was filled with impacted allogenic bone chips and the asymmetric cup was augmented with a 50-mm intramedullary iliac press-fit stem and multiple screws. (C) Radiographic imaging 24 months postoperatively revealed a stable implant with well-integrated bone grafts (HHS: 46 preoperatively, 66 postoperatively; OT 150 min). Full article ">Figure 4
(A) A.p. and axial radiograph of a 66-year-old male patient with significant medial cup protrusion. The intraoperative defect classification revealed an intact anterior and posterior column with supportive rim elements (Paprosky type IIC). (B) The defect was filled with impacted allogeneic bone chips obtained from two femoral heads. A.p. and axial radiographs 12 months postoperatively demonstrate sufficient integration and remodeling of the graft and reconstruction of the anatomical center of rotation. (C) Pre-, intra-, and postoperative views showing the skin incision used for DAA revision arthroplasty and its position relative to the previously used approach (HHS: 66 preoperatively, 100 postoperatively; OT 149 min). Full article ">Figure 5
(A) A.p. and axial radiograph of an 80-year-old female patient presenting with transverse periprosthetic fracture and medial protrusion of the cup two weeks after cementless hip arthroplasty. (B) The patient suffered from multiple co-morbidities and her BMI (body mass index) was 39 kg/m2. After removal of the loose acetabular and femoral implant via the DAA, the acetabular fracture line was visible. To prevent iatrogenic lesions of the TFL during stem extraction, a “tensor-snip” was performed. The screw fixation through the implant’s iliac flange was performed by insertion of the screws via the DAA and subsequent fixation with a long screwdriver introduced via a gluteal stab incision in order to avoid any proximal extension of the approach. (C) Radiographic imaging (a.p. and axial view) 18 months postoperatively show a well-fixed acetabular implant (HHS: nine preoperatively, 64 postoperatively; OT 126 min). Full article ">Figure 6
Kaplan–Meier curves demonstrating estimated overall implant survival (A) and revision-free survival (B). Full article ">Figure 7
Scatter plot demonstrating the location of the center of rotation pre- (black dots) and postoperatively (white dots). The point of origin (0/0 mm) represents the aCOR. Full article ">

Journal Menu

Journal Browser

J. Clin. Med., Volume 9, Issue 9 (September 2020) – 380 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI