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J. Clin. Med., Volume 9, Issue 4 (April 2020) – 42 articles

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Open AccessArticle
Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction
J. Clin. Med. 2020, 9(4), 937; https://doi.org/10.3390/jcm9040937 (registering DOI) - 29 Mar 2020
Abstract
Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of [...] Read more.
Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases. Full article
(This article belongs to the Special Issue Characterization and Clinical Management of Dilated Cardiomyopathy)
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Open AccessArticle
Local and Central Evaluation of HER2 Positivity and Clinical Outcome in Advanced Gastric and Gastroesophageal Cancer—Results from the AGMT GASTRIC-5 Registry
J. Clin. Med. 2020, 9(4), 935; https://doi.org/10.3390/jcm9040935 (registering DOI) - 29 Mar 2020
Abstract
Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still [...] Read more.
Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870–24,530) vs. 6.9 months (95% CI: 3.980–9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort. Full article
(This article belongs to the Special Issue Novel Pathways and Targeted Therapies for Gastric Cancer)
Open AccessArticle
Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma
J. Clin. Med. 2020, 9(4), 936; https://doi.org/10.3390/jcm9040936 (registering DOI) - 28 Mar 2020
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Abstract
The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We [...] Read more.
The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC. Full article
(This article belongs to the Special Issue Prevention and Treatment of Sarcopenia)
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Open AccessArticle
MRI study of paraspinal muscles in patients with Amyotrophic Lateral Sclerosis (ALS)
J. Clin. Med. 2020, 9(4), 934; https://doi.org/10.3390/jcm9040934 (registering DOI) - 28 Mar 2020
Viewed by 128
Abstract
Background: the study of paraspinal muscles is pivotal for the diagnosis and staging of Amyotrophic Lateral Sclerosis (ALS), and is usually performed by electromyography. Objective: to evaluate the role of paraspinal muscle MRI as a diagnostic biomarker in ALS. Methods: we evaluated T1-w [...] Read more.
Background: the study of paraspinal muscles is pivotal for the diagnosis and staging of Amyotrophic Lateral Sclerosis (ALS), and is usually performed by electromyography. Objective: to evaluate the role of paraspinal muscle MRI as a diagnostic biomarker in ALS. Methods: we evaluated T1-w images of newly diagnosed ALS patients (n = 14), age-matched healthy controls (n = 11), patients affected by inflammatory myopathy (n = 10), and lumbar radiculopathy (n = 19), and compared them semiquantitatively by using the Mercuri Scale. Results: a significant difference in the appearance of the psoas muscle was observed between ALS patients and patients with radiculopathy (p = 0.003); after stratifying ALS patients into spinal and bulbar onsets, we found a significant difference in the appearance of the longissimus dorsi muscle between the spinal onset ALS subgroup and bulbar onset ALS subgroup (p = 0.0245), while no difference was found for multifidus (p = 0.1441), iliocostal (p = 0.0655), and psoas muscles (p = 0.0813) between the cohort subgroups. Conclusions: paraspinal T1-w MRI could help to distinguish spinal ALS patients from healthy and pathological controls. Specifically, the study of longissimus dorsi could play the role of a diagnostic ALS biomarker. Full article
Open AccessArticle
Patient Characteristics, Treatment and Outcome in Non-Ischemic vs. Ischemic Cardiogenic Shock
J. Clin. Med. 2020, 9(4), 931; https://doi.org/10.3390/jcm9040931 (registering DOI) - 28 Mar 2020
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Abstract
: Aim: Evidence on non-ischemic cardiogenic shock (CS) is scarce. The aim of this study was to investigate differences in patient characteristics, use of treatments and outcomes in patients with non-ischemic vs. ischemic CS. Methods: Patients with CS admitted between October 2009 and [...] Read more.
: Aim: Evidence on non-ischemic cardiogenic shock (CS) is scarce. The aim of this study was to investigate differences in patient characteristics, use of treatments and outcomes in patients with non-ischemic vs. ischemic CS. Methods: Patients with CS admitted between October 2009 and October 2017 were identified and stratified as non-ischemic/ischemic CS based on the absence/presence of acute myocardial infarction. Logistic/Cox regression models were fitted to investigate the association between non-ischemic CS and patient characteristics, use of treatments and 30-day in-hospital mortality. Results: A total of 978 patients were enrolled in this study; median age was 70 (interquartile range 58, 79) years and 70% were male. Of these, 505 patients (52%) had non-ischemic CS. Patients with non-ischemic CS were more likely to be younger and female; were less likely to be active smokers, to have diabetes or decreased renal function, but more likely to have a history of myocardial infarction; and they were more likely to present with unfavorable hemodynamics and with mechanical ventilation. Regarding treatments, patients with non-ischemic CS were more likely to be treated with catecholamines, but less likely to be treated with extracorporeal membrane oxygenation or percutaneous left-ventricular assist devices. After adjustment for multiple relevant confounders, non-ischemic CS was associated with a significant increase in the risk of 30-day in-hospital mortality (hazard ratio 1.14, 95% confidence interval 1.04–1.24, p < 0.01). Conclusion: In this large study, non-ischemic CS accounted for more than 50% of all CS cases. Non-ischemic CS was not only associated with relevant differences in patient characteristics and use of treatments, but also with a worse prognosis. These findings highlight the need for effective treatment strategies for patients with non-ischemic CS. Full article
(This article belongs to the Special Issue Management of Cardiogenic Shock)
Open AccessReview
Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?
J. Clin. Med. 2020, 9(4), 930; https://doi.org/10.3390/jcm9040930 (registering DOI) - 28 Mar 2020
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Abstract
The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth [...] Read more.
The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells’ (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC. Full article
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Open AccessArticle
Salivary Biomarkers and Their Correlation with Pain and Stress in Patients with Burning Mouth Syndrome
J. Clin. Med. 2020, 9(4), 929; https://doi.org/10.3390/jcm9040929 (registering DOI) - 28 Mar 2020
Viewed by 146
Abstract
Objective: To evaluate a panel of salivary analytes involving biomarkers of inflammation, stress, immune system and antioxidant status in patients with burning mouth syndrome (BMS) and to study their relationship with clinical variables. Materials and Methods: A total of 51 patients with BMS [...] Read more.
Objective: To evaluate a panel of salivary analytes involving biomarkers of inflammation, stress, immune system and antioxidant status in patients with burning mouth syndrome (BMS) and to study their relationship with clinical variables. Materials and Methods: A total of 51 patients with BMS and 31 controls were consecutively enrolled in the study, with the recording of oral habits, the severity of pain using a visual analogue scale (VAS), the Hospital Anxiety and Depression (HAD) score and the Oral Health Impact Profile-14 (OHIP14) score. Resting whole saliva was collected with the drainage technique, followed by the measurement of 11 biomarkers. Results: The salivary flow was higher in patients with BMS. Among all the biomarkers studied, significantly higher levels of alpha-amylase, immunoglobulin A (IgA), and macrophage inflammatory protein-4 (MIP4) and lower levels of uric acid and ferric reducing activity of plasma (FRAP) were observed in the saliva of patients with BMS and the controls (p < 0.05 in all cases). Positive correlations were found between pain, oral quality of life and anxiety scores and salivary biomarkers. Conclusions: BMS is associated with changes in salivary biomarkers of inflammation, oxidative stress and stress, being related to the degree of pain and anxiety. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
Open AccessArticle
Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study
J. Clin. Med. 2020, 9(4), 928; https://doi.org/10.3390/jcm9040928 (registering DOI) - 28 Mar 2020
Viewed by 156
Abstract
Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same [...] Read more.
Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75–300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case–control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54–0.88) for >1 month PPI use and 2.65 (1.62–4.3) for ≤1 month PPI use. Among the latter group, ORs (95% CIs) were 3.05 (1.75–5.33) for PPI initiation after start of aspirin therapy, and 1.66 (0.63–4.36) for PPI initiation on/before start of aspirin therapy. For LGIB (n = 1428), ORs (95% CIs) were 0.98 (0.81–1.17) for >1 month PPI use and 1.12 (0.73–1.71) for ≤1 month PPI use. Among low-dose aspirin users, maintaining PPI use (>1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk. Full article
(This article belongs to the Special Issue New Trends and Advances in Non-Variceal Gastrointestinal Bleeding)
Open AccessArticle
Calprotectin and Receptor for Advanced Glycation End Products as a Potential Biomarker in Abdominal Aortic Aneurysm
J. Clin. Med. 2020, 9(4), 927; https://doi.org/10.3390/jcm9040927 (registering DOI) - 28 Mar 2020
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Abstract
Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the [...] Read more.
Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the diameter of the abdominal aorta was found. The purpose of this study was to investigate whether calprotectin and the RAGE plasma level may be a biomarker of human AAA occurrence. We determined two groups of research participants: a group of 32 patients aged 53–88 undergoing primary endovascular aneurysm repair and a control group of 43 volunteers aged 59–82 without the AAA. All the patients from the study group had their blood samples drawn in order to determine the level of calprotectin and RAGE in plasma. The second follow-up examination was carried out after three months. The concentration of calprotectin and RAGE in plasma was determined with the use of the immunoenzymatic method (ELISA). The study showed that patients with the AAA had significantly higher mean calprotectin and RAGE plasma levels (p = 0.0001 and p = 0.0002, respectively) as compared to the control group. After the AAA repair operations, the level of concentration of the calprotectin decreased significantly (p = 0.0002). So far, no studies on the connection between the increase of the calprotectin and RAGE in the patient’s plasma with the AAA have been published. Calprotectin may be a promising biomarker related to the occurrence of AAA. Larger studies are needed to fully elucidate and confirm the role of calprotectin in the development and progression of the aneurysm. Full article
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Open AccessArticle
Can an Observational Gait Scale Produce a Result Consistent with Symmetry Indexes Obtained from 3-Dimensional Gait Analysis?: A Concurrent Validity Study
J. Clin. Med. 2020, 9(4), 926; https://doi.org/10.3390/jcm9040926 (registering DOI) - 28 Mar 2020
Viewed by 110
Abstract
To investigate whether a simple observational tool may be a substitute to the time-consuming and costly 3-dimensional (3D) analysis, the study applied the Wisconsin Gait Scale (WGS), enabling assessment which is highly consistent with 3D gait parameters in patients after a stroke. The [...] Read more.
To investigate whether a simple observational tool may be a substitute to the time-consuming and costly 3-dimensional (3D) analysis, the study applied the Wisconsin Gait Scale (WGS), enabling assessment which is highly consistent with 3D gait parameters in patients after a stroke. The aim of this study was to determine whether, and to what extent, observational information obtained from WGS-based assessment can be applied to predict results of 3D gait analysis for selected symmetry indicators related to spatiotemporal and kinematic gait parameters. Fifty patients at a chronic stage of recovery post-stroke were enrolled in the study. The spatiotemporal and kinematic gait parameters were measured using a movement analysis system. The symmetry index (SI), was calculated for selected gait parameters. The patients’ gait was evaluated by means of the WGS. It was shown that stance % SI, as well as hip and knee flexion-extension range of motion SI can most effectively be substituted by WGS-based estimations (coefficient of determination exceeding 80%). It was shown that information acquired based on the WGS can be used to obtain results comparable to those achieved in 3D assessment for selected SIs of spatiotemporal and kinematic gait parameters. The study confirms that observation of gait using the WGS, which is an ordinal scale, is consistent with the selected aims of 3D assessment. Therefore, the scale can be used as a complementary tool in gait assessment. Full article
(This article belongs to the Section Clinical Neurology)
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Open AccessArticle
Associations between the Quality of Life and Nasal Polyp Size in Patients Suffering from Chronic Rhinosinusitis without Nasal Polyps, with Nasal Polyps or Aspirin-Exacerbated Respiratory Disease
J. Clin. Med. 2020, 9(4), 925; https://doi.org/10.3390/jcm9040925 (registering DOI) - 28 Mar 2020
Viewed by 113
Abstract
Chronic rhinosinusitis (CRS) is a common disease that substantially impairs the quality of life (QoL). Here, we aimed to assess patients’ QoL in different subtypes of CRS and correlated this with nasal polyp size to improve the clinical understanding of the burden of [...] Read more.
Chronic rhinosinusitis (CRS) is a common disease that substantially impairs the quality of life (QoL). Here, we aimed to assess patients’ QoL in different subtypes of CRS and correlated this with nasal polyp size to improve the clinical understanding of the burden of disease. In this retrospective single-center study, 107 patients with the following diagnoses were analyzed: CRS without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP), or aspirin-exacerbated respiratory disease (AERD). Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) scores and their correlation with endoscopic Total Polyp Scores (TPS) were evaluated. The mean SNOT-20 GAV scores were highest in patients with AERD (AERD = 43.4, CRSwNP = 36.3, CRSsNP = 30.9). A statistically significant correlation of total SNOT-20 GAV score with TPS was observed in CRSwNP patients (r = 0.3398, p = 0.0195), but not in AERD patients (r = 0.2341, p = 0.1407). When analyzing single SNOT-20 parameters, a strong correlation with TPS was observed for blockage/congestion of the nose, particularly in AERD patients (r = 0.65, p < 0.0001). The impact of nasal polyp size on the QoL differs amongst the subgroups of CRS. Nasal symptoms have the greatest impact on QoL in patients suffering from AERD. CRSwNP and AERD patients should be separately analyzed in clinical investigations and interpretations due to significant differences in QoL. Full article
(This article belongs to the Section Otolaryngology)
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Open AccessArticle
Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress
J. Clin. Med. 2020, 9(4), 924; https://doi.org/10.3390/jcm9040924 (registering DOI) - 28 Mar 2020
Viewed by 118
Abstract
A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, [...] Read more.
A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis. In addition to providing a cell and protein-rich environment for cancer growth and progression, ascitic fluid also confers physical stress on tumors. An understudied area in ovarian cancer research is the impact of fluid shear stress on treatment failure. Here, we investigate the effect of fluid shear stress on response to platinum-based chemotherapy and the modulation of molecular pathways associated with aggressive disease in a perfusion model for adherent 3D ovarian cancer nodules. Resistance to carboplatin is observed under flow with a concomitant increase in the expression and activation of the epidermal growth factor receptor (EGFR) as well as downstream signaling members mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and extracellular signal-regulated kinase (ERK). The uptake of platinum by the 3D ovarian cancer nodules was significantly higher in flow cultures compared to static cultures. A downregulation of phospho-focal adhesion kinase (p-FAK), vinculin, and phospho-paxillin was observed following carboplatin treatment in both flow and static cultures. Interestingly, low-dose anti-EGFR photoimmunotherapy (PIT), a targeted photochemical modality, was found to be equally effective in ovarian tumors grown under flow and static conditions. These findings highlight the need to further develop PIT-based combinations that target the EGFR, and sensitize ovarian cancers to chemotherapy in the context of flow-induced shear stress. Full article
(This article belongs to the Special Issue The Past, Present and Future of Photodynamic Therapy for Cancers)
Open AccessReview
Prevention and Management of the Post-Thrombotic Syndrome
J. Clin. Med. 2020, 9(4), 923; https://doi.org/10.3390/jcm9040923 (registering DOI) - 27 Mar 2020
Viewed by 127
Abstract
The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency secondary to prior deep vein thrombosis (DVT). It affects up to 50% of patients after proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention [...] Read more.
The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency secondary to prior deep vein thrombosis (DVT). It affects up to 50% of patients after proximal DVT. There is no effective treatment of established PTS and its management lies in its prevention after DVT. Optimal anticoagulation is key for PTS prevention. Among anticoagulants, low-molecular-weight heparins have anti-inflammatory properties, and have a particularly attractive profile. Elastic compression stockings (ECS) may be helpful for treating acute DVT symptoms but their benefits for PTS prevention are debated. Catheter-directed techniques reduce acute DVT symptoms and might reduce the risk of moderate–severe PTS in the long term in patients with ilio-femoral DVT at low risk of bleeding. Statins may decrease the risk of PTS, but current evidence is lacking. Treatment of PTS is based on the use of ECS and lifestyle measures such as leg elevation, weight loss and exercise. Venoactive medications may be helpful and research is ongoing. Interventional techniques to treat PTS should be reserved for highly selected patients with chronic iliac obstruction or greater saphenous vein reflux, but have not yet been assessed by robust clinical trials. Full article
(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)
Open AccessArticle
Circadian Patterns in Postvoid Residual and Voided Percentage Among Older Women with Urinary Incontinence
J. Clin. Med. 2020, 9(4), 922; https://doi.org/10.3390/jcm9040922 (registering DOI) - 27 Mar 2020
Viewed by 137
Abstract
Background: Women with urinary incontinence incur an increased risk of elevated postvoid residual (PVR) volume and impaired voiding efficiency (i.e., voided percentage (Void%)), but the clinical significance of these parameters remains poorly described. Further characterization of PVR and voiding efficiency may thus be [...] Read more.
Background: Women with urinary incontinence incur an increased risk of elevated postvoid residual (PVR) volume and impaired voiding efficiency (i.e., voided percentage (Void%)), but the clinical significance of these parameters remains poorly described. Further characterization of PVR and voiding efficiency may thus be useful in refining the evaluation and management of urinary incontinence. This study aims to explore possible circadian variations in PVR and Void% in older women with stress (SUI), urge (UUI) and mixed urinary incontinence (MUI). Methods: A single center prospective study which enrolled a convenience sample of 90 older women who consulted a tertiary referral hospital for urinary incontinence. Participants underwent an extensive medical interview and were hospitalized to complete a 24-h frequency-volume chart (FVC) with PVR measurement after each void (FVCPVR). Results: FVCPVR analysis demonstrated no differences in mean PVR and Void% between patients with SUI, UUI and MUI. Likewise, no daytime or nighttime differences were observed in mean PVR or Void% within or between groups. Conclusions: No evidence of circadian variation in PVR or Void% was observed in older women with SUI, UUI or MUI. Full article
Open AccessReview
Effective Asthma Management: Is It Time to Let the AIR out of SABA?
J. Clin. Med. 2020, 9(4), 921; https://doi.org/10.3390/jcm9040921 (registering DOI) - 27 Mar 2020
Viewed by 178
Abstract
For years, standard asthma treatment has included short acting beta agonists (SABA), including as monotherapy in patients with mild asthma symptoms. In the Global Initiative for Asthma 2019 strategy for the management of asthma, the authors recommended a significant departure from the traditional [...] Read more.
For years, standard asthma treatment has included short acting beta agonists (SABA), including as monotherapy in patients with mild asthma symptoms. In the Global Initiative for Asthma 2019 strategy for the management of asthma, the authors recommended a significant departure from the traditional treatments. Short acting beta agonists (SABAs) are no longer recommended as the preferred reliever for patients when they are symptomatic and should not be used at all as monotherapy because of significant safety concerns and poor outcomes. Instead, the more appropriate course is the use of a combined inhaled corticosteroid–fast acting beta agonist as a reliever. This paper discusses the issues associated with the use of SABA, the reasons that patients over-use SABA, difficulties that can be expected in overcoming SABA over-reliance in patients, and our evolving understanding of the use of “anti-inflammatory relievers” in our patients with asthma. Full article
Open AccessArticle
The Public Health Burden of Cardiomyopathies: Insights from a Nationwide Inpatient Study
J. Clin. Med. 2020, 9(4), 920; https://doi.org/10.3390/jcm9040920 (registering DOI) - 27 Mar 2020
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Abstract
Cardiomyopathies are responsible for heart failure and sudden cardiac death, but epidemiological data are scarce and the public health burden may be underestimated. We studied aggregating data from all public or private hospitals in France. Patients were categorized from relevant ICD-10 codes into [...] Read more.
Cardiomyopathies are responsible for heart failure and sudden cardiac death, but epidemiological data are scarce and the public health burden may be underestimated. We studied aggregating data from all public or private hospitals in France. Patients were categorized from relevant ICD-10 codes into dilated, hypertrophic, restrictive, or other cardiomyopathies (DCM, HCM, RCM, or OCM, respectively). Between 2008 and 2015, a total of 326,461 distinct patients had cardiomyopathy-related hospitalizations. The hospital-based prevalence of cardiomyopathy was 809 per million inhabitants (PMI) per year, including 428 PMI for DCM, 101 PMI for HCM, 26 PMI for RCM, and 253 PMI for OCM. Patients with cardiomyopathies accounted for 51% of all heart transplants, 33% of defibrillator implantations, 38% of mechanical circulatory supports, and 11.3% of hospitalizations for heart failure. In patients less than 40 years of age, these figures were 71%, 51%, 63%, and 23%, respectively. Over 2008–2015 and considering all cardiomyopathies, there was a significant increase for heart transplant (average annual percentage change, AAPC: +3.86%, p = 0.0015) and for defibrillator implantation (AAPC: +6.98%, p < 0.0001), and a significant decrease of in-hospital mortality (AAPC: −4.7%, p = 0.0002). This nationwide study shows that cardiomyopathies constitute an important cause of hospitalization, with increasing invasive therapeutic procedures and decreasing mortality. Full article
(This article belongs to the Section Cardiology)
Open AccessReview
Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug–Drug Interactions
J. Clin. Med. 2020, 9(4), 919; https://doi.org/10.3390/jcm9040919 (registering DOI) - 27 Mar 2020
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Abstract
Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC [...] Read more.
Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy. Full article
(This article belongs to the Section Pharmacology)
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Open AccessArticle
The Vascular Side of Chronic Bed Rest: When a Therapeutic Approach Becomes Deleterious
J. Clin. Med. 2020, 9(4), 918; https://doi.org/10.3390/jcm9040918 (registering DOI) - 27 Mar 2020
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Abstract
The interplay between chronic constraint and advanced aging on blood flow, shear-rate, vascular function, nitric oxide (NO)-bioavailability, microcirculation, and vascular inflammation factors is still a matter of debate. Ninety-eight individuals (Young, n=28, 23±3yrs; Old, n=36, 85±7yrs; Bedridden, n=34, 88±6yrs) were [...] Read more.
The interplay between chronic constraint and advanced aging on blood flow, shear-rate, vascular function, nitric oxide (NO)-bioavailability, microcirculation, and vascular inflammation factors is still a matter of debate. Ninety-eight individuals (Young, n=28, 23±3yrs; Old, n=36, 85±7yrs; Bedridden, n=34, 88±6yrs) were included in the study. The bedridden group included old individuals chronically confined to bed (3.8±2.3yrs). A blood sample was collected and analyzed for plasma nitrate, and vascular inflammatory markers. Hyperemic response (∆peak) during the single passive leg movement (sPLM) test was used to measure vascular function. Skeletal muscle total hemoglobin was measured at the vastus lateralis during the sPLM test, by means of near infrared spectroscopy (NIRS). Bedridden subjects revealed a depletion of plasma nitrates compared with Old (-23.8%) and Young (-31.1%). Blood flow was lower in the Bedridden in comparison to Old (-20.1%) and Young (-31.7%). Bedridden presented lower sPLM ∆peak compared Old (-72.5%) and the Young (-83.3%). ∆peak of NIRS total hemoglobin was lower in the Bedridden compared to that in the Young (-133%). All vascular inflammatory markers except IL-6 were significantly worse in the Bedridden compared to Old and Young. No differences were found between the Old and Young in inflammatory markers. Results of this study confirm that chronic physical constraint induces an exacerbation of vascular disfunction and differential regulation of vascular-related inflammatory markers. The mechanisms involved in these negative adaptations seems to be associated with endothelial dysfunction and consequent diminished NO-bioavailability likely caused by the reduced shear-rate consequential to long-term reduction of physical activity. Full article
(This article belongs to the Special Issue Endothelial Cell Metabolism Under Pathological Conditions)
Open AccessArticle
Thulium Laser Vapoenucleation of the Prostate (ThuVEP) in Men at High Cardiovascular Risk and on Antithrombotic Therapy: A Single-Center Experience
J. Clin. Med. 2020, 9(4), 917; https://doi.org/10.3390/jcm9040917 (registering DOI) - 27 Mar 2020
Viewed by 147
Abstract
Bleeding is the most common complication of transurethral resection of the prostate and simple open prostatectomy, especially in men on antiplatelet/anticoagulant therapy. The present study aimed to evaluate the safety and effectiveness of thulium laser vapoenucleation of the prostate (ThuVEP) for benign prostatic [...] Read more.
Bleeding is the most common complication of transurethral resection of the prostate and simple open prostatectomy, especially in men on antiplatelet/anticoagulant therapy. The present study aimed to evaluate the safety and effectiveness of thulium laser vapoenucleation of the prostate (ThuVEP) for benign prostatic hyperplasia in patients on chronic antithrombotic medications. Between January 2015 and December 2019, 88 men underwent the procedure under antithrombotic agents in our center. The mean age was 74.7 ± 6.1 years. Median prostate volume was 66.5 mL. Patients on oral anticoagulants were bridged to low-molecular-weight heparin (n = 35). Aspirin (n = 39), clopidogrel (n = 10), and ticlopidine (n = 4) were maintained. Of the patients, 69.3% had an American Society of Anesthesiologists score ≥ 3. Blood loss at 24 h was comparable in all groups. Median catheterization length and postoperative stays were 2 and 3 days respectively. Acute cardiovascular events occurred in 2 patients (2.3%). Of the patients, 4 required prolonged bladder irrigation, 2 required blood transfusions, 1 required a cystoscopy for bleeding control, and 1 required a suprapubic cystostomy for blood clot evacuation. No patients died within 30 days of being discharged. Late complications occurred in 3 (3.8%) patients (1 optical urethrotomy and 1 bladder neck incision for stenosis; 1 acute myocardial infarction). All follow-up visits (1, 6, and 12-month) showed a significant improvement in all urinary parameters compared to baseline. ThuVEP appears to be a feasible surgical option in high-risk patients on antithrombotic regimens, with acceptable postoperative morbidity, good functional outcome, and low incidence of medium-term reoperation rate. Full article
(This article belongs to the Special Issue Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia)
Open AccessArticle
Assessment of the Efficacy of Lowering LDL Cholesterol with Rosuvastatin 10 mg in Four Korean Statin Benefit Groups as per ACC/AHA Guidelines (NewStaR4G)
J. Clin. Med. 2020, 9(4), 916; https://doi.org/10.3390/jcm9040916 (registering DOI) - 27 Mar 2020
Viewed by 95
Abstract
The American College of Cardiology and American Heart Association (ACC/AHA) guidelines identified four statin benefit groups on the basis of atherosclerotic cardiovascular disease risk reduction and proposed statin therapy by evidence-based intensity. Although these guidelines used randomized controlled trials with hard outcomes as [...] Read more.
The American College of Cardiology and American Heart Association (ACC/AHA) guidelines identified four statin benefit groups on the basis of atherosclerotic cardiovascular disease risk reduction and proposed statin therapy by evidence-based intensity. Although these guidelines used randomized controlled trials with hard outcomes as exclusive evidence for its recommendations, a limited number of studies conducted in Asian countries makes its application of treatment strategy, intensity, and statin doses uncertain in these population. This prospective, multicenter study aimed to evaluate the efficacy of rosuvastatin 10 mg in the four statin benefit groups requiring high- or moderate-intensity statin therapy according to the ACC/AHA guidelines in the Korean population. The primary endpoint was percentage reduction in low-density lipoprotein (LDL) cholesterol. Secondary endpoints were percentage reduction in other lipids and achievement of ≥50% reduction in LDL cholesterol. Rosuvastatin 10 mg lowered LDL cholesterol by 61.4 mg/dL, a 44.9% decrease from baseline after eight weeks. Reduction of LDL cholesterol ≥50% was achieved in 46.3% of patients. Rosuvastatin 10 mg was generally well tolerated. In the Korean population, rosuvastatin 10 mg was favorable and tolerant in lowering LDL cholesterol in the four statin benefit groups requiring high- or moderate-intensity statin therapy according to the ACC/AHA guidelines. Full article
(This article belongs to the Special Issue Current and Emerging Uses of Statins in Clinical Therapeutics)
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Open AccessArticle
Deproteinization as a Rapid Method of Saliva Purification for the Determination of Carbamazepine and Carbamazepine-10,11 Epoxide
J. Clin. Med. 2020, 9(4), 915; https://doi.org/10.3390/jcm9040915 (registering DOI) - 27 Mar 2020
Viewed by 101
Abstract
Saliva is a valuable diagnostic material that, in some cases, may replace blood. However, because of its different composition, its use requires the development of new, or the modification of existing, extraction procedures. Therefore, the aim of the study was to develop a [...] Read more.
Saliva is a valuable diagnostic material that, in some cases, may replace blood. However, because of its different composition, its use requires the development of new, or the modification of existing, extraction procedures. Therefore, the aim of the study was to develop a method of saliva purification that would enable the determination of carbamazepine and its metabolite, carbamazepine-10,11 epoxide. When comparing two methods of sample purification (Solid Phase Extration (SPE) and deproteinization), it was found that the second method yielded more favorable results. A 1% formic acid solution in acetonitrile was used for extraction. The samples were shaken and centrifuged, and the supernatant obtained was evaporated and dissolved in a mobile phase, then chromatographically analyzed. The developed method was validated by determining its linearity in the range of 10–5000 ng/mL for both analytes. Intra- and inter-day precision did not exceed 14%. In order to check the usefulness of the method, both analytes were determined in the saliva samples from 20 patients treated with carbamazepine. The content of both analytes was detected and determined in all of the tested samples of saliva. It was found that the method developed is rapid, sensitive, reliable, and can be used to monitor the concentration of carbamazepine and metabolite in patients’ saliva. Full article
(This article belongs to the Section Stomatology)
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Open AccessReview
The Effect of Exercise Training on Brain Structure and Function in Older Adults: A Systematic Review Based on Evidence from Randomized Control Trials
J. Clin. Med. 2020, 9(4), 914; https://doi.org/10.3390/jcm9040914 (registering DOI) - 27 Mar 2020
Viewed by 132
Abstract
Accumulating evidence suggests that exercise training is associated with improvements in brain health in older adults, yet the extant literature is insufficient in detailing why exercise training facilitates brain structure and function. Specifically, few studies have employed the FITT-VP principle (i.e., Frequency, Intensity, [...] Read more.
Accumulating evidence suggests that exercise training is associated with improvements in brain health in older adults, yet the extant literature is insufficient in detailing why exercise training facilitates brain structure and function. Specifically, few studies have employed the FITT-VP principle (i.e., Frequency, Intensity, Time, Type, Volume, and Progression) to characterize the exercise exposure, thus research is yet to specify which characteristics of exercise training benefit brain outcomes. To determine whether exercise training is consequential to cognitive and brain outcomes, we conducted a systematic review investigating the effects of exercise training on brain structure and function in older adults. PubMed and Scopus were searched from inception to February 2020, and study quality was assessed using the Cochrane risk-of-bias tool. A total of 24 randomized controlled trials were included. This systematic review indicates that older adults involved in exercise training may derive general benefits to brain health, as reflected by intervention-induced changes in brain structure and function. However, such benefits are dependent upon the dose of the exercise intervention. Importantly, current evidence remains limited for applied exercise prescriptions (e.g., volume, progression) and future research is needed to clarify the effects of exercise training on cognitive and brain outcomes in older adults. Full article
Open AccessArticle
Physiopathological Bases of the Disease Caused by HACE1 Mutations: Alterations in Autophagy, Mitophagy and Oxidative Stress Response
J. Clin. Med. 2020, 9(4), 913; https://doi.org/10.3390/jcm9040913 (registering DOI) - 26 Mar 2020
Viewed by 177
Abstract
Recessive HACE1 mutations are associated with a severe neurodevelopmental disorder (OMIM: 616756). However, the physiopathologycal bases of the disease are yet to be completely clarified. Whole-exome sequencing identified homozygous HACE1 mutations (c.240C>A, p.Cys80Ter) in a patient with brain atrophy, psychomotor retardation and 3-methylglutaconic [...] Read more.
Recessive HACE1 mutations are associated with a severe neurodevelopmental disorder (OMIM: 616756). However, the physiopathologycal bases of the disease are yet to be completely clarified. Whole-exome sequencing identified homozygous HACE1 mutations (c.240C>A, p.Cys80Ter) in a patient with brain atrophy, psychomotor retardation and 3-methylglutaconic aciduria, a biomarker of mitochondrial dysfunction. To elucidate the pathomechanisms underlying HACE1 deficiency, a comprehensive molecular analysis was performed in patient fibroblasts. Western Blot demonstrated the deleterious effect of the mutation, as the complete absence of HACE1 protein was observed. Immunofluorescence studies showed an increased number of LC3 puncta together with the normal initiation of the autophagic cascade, indicating a reduction in the autophagic flux. Oxidative stress response was also impaired in HACE1 fibroblasts, as shown by the reduced NQO1 and Hmox1 mRNA levels observed in H2O2-treated cells. High levels of lipid peroxidation, consistent with accumulated oxidative damage, were also detected. Although the patient phenotype could resemble a mitochondrial defect, the analysis of the mitochondrial function showed no major abnormalities. However, an important increase in mitochondrial oxidative stress markers and a strong reduction in the mitophagic flux were observed, suggesting that the recycling of damaged mitochondria might be targeted in HACE1 cells. In summary, we demonstrate for the first time that the impairment of autophagy, mitophagy and oxidative damage response might be involved in the pathogenesis of HACE1 deficiency. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessReview
Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes
J. Clin. Med. 2020, 9(4), 912; https://doi.org/10.3390/jcm9040912 (registering DOI) - 26 Mar 2020
Viewed by 166
Abstract
Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage [...] Read more.
Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by targeted treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (e.g., Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, and DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial (dys)functions, inflammatory markers, biomarkers of both oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of the main trials focused on the cardiovascular safety of these drugs from the CV standpoint. Full article
(This article belongs to the Section Endocrinology & Metabolism)
Open AccessArticle
Ventricular Repolarization is Associated with Cognitive Function, but Not with Cognitive Decline and Brain Magnetic Resonance Imaging (MRI) Measurements in Older Adults
J. Clin. Med. 2020, 9(4), 911; https://doi.org/10.3390/jcm9040911 (registering DOI) - 26 Mar 2020
Viewed by 186
Abstract
We aimed to investigate the cross-sectional and longitudinal associations of electrocardiogram (ECG)-based QT, QTc, JT, JTc, and QRS intervals with cognitive function and brain magnetic resonance imaging (MRI) measurements in a cohort of older individuals at increased risk for cardiovascular disease, but free [...] Read more.
We aimed to investigate the cross-sectional and longitudinal associations of electrocardiogram (ECG)-based QT, QTc, JT, JTc, and QRS intervals with cognitive function and brain magnetic resonance imaging (MRI) measurements in a cohort of older individuals at increased risk for cardiovascular disease, but free of known arrhythmias. We studied 4627 participants (54% female, mean age 75 years) enrolled in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Ten-second ECGs were conducted at baseline. Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Structural MRIs were conducted in a subgroup of 535 participants. Analyses were performed with multivariable (repeated) linear regression models and adjusted for cardiovascular risk-factors, co-morbidities, and cardiovascular drug use. At baseline, longer QT, JT, JTc—but not QTc and QRS intervals—were associated with a worse cognitive performance. Most notably, on the Stroop Test, participants performed 3.02 (95% CI 0.31; 5.73) seconds worse per standard deviation higher QT interval, independent of cardiovascular risk factors and medication use. There was no association between longer ventricular de- or repolarization and structural brain measurements. Therefore, specifically ventricular repolarization was associated with worse cognitive performance in older individuals at baseline but not during follow-up. Full article
Open AccessArticle
Methotrexate Decreases the Level of PCSK9—A Novel Indicator of the Risk of Proatherogenic Lipid Profile in Psoriasis. The Preliminary Data
J. Clin. Med. 2020, 9(4), 910; https://doi.org/10.3390/jcm9040910 (registering DOI) - 26 Mar 2020
Viewed by 169
Abstract
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) exerts an important role in inflammatory processes, lipids homeostasis, and cardiometabolic disorders that are closely associated with psoriasis. The aim of the study was to analyze the clinical and diagnostic value of serum PCSK9 concentrations and [...] Read more.
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) exerts an important role in inflammatory processes, lipids homeostasis, and cardiometabolic disorders that are closely associated with psoriasis. The aim of the study was to analyze the clinical and diagnostic value of serum PCSK9 concentrations and their connections with disease severity, inflammation, metabolic syndrome, and impact of systemic therapies in psoriatic patients. The study enrolled thirty-five patients with active plaque-type psoriasis and eighteen healthy volunteers served as controls. Blood samples were obtained before and after 12 weeks of treatment with methotrexate or acitretin. Serum PCSK9 concentrations were measured by the ELISA (Enzyme-Linked Immunosorbent Assay) commercial kits. Morphological and biochemical parameters were assayed using routine laboratory techniques. Psoriatic patients showed significantly elevated levels of PCSK9 compared to controls (p < 0.01), mostly in patients with a mild and moderate course of psoriasis. PCSK9 concentrations correlated positively with BMI and triglyceride levels (p < 0.05). Interestingly, PCSK9 had a strong negative correlation with low-density lipoprotein levels and total cholesterol (p < 0.05). Three months of monotherapy with methotrexate significantly reduced PCSK9 level (p < 0.05), on the contrary, the acitretin group showed a further increase of PCSK9 levels (p < 0.05). PCSK9 seems to be a novel marker of psoriasis and a putative explanation of lipid disturbances, which are common in patients with psoriasis and are vital for the further developing of metabolic syndrome. Methotrexate should be considered as a treatment of choice in patients with an elevated PCSK9 concentration. Full article
Open AccessReview
Prevalence of Depression in Coronary Artery Bypass Surgery: A Systematic Review and Meta-Analysis
J. Clin. Med. 2020, 9(4), 909; https://doi.org/10.3390/jcm9040909 (registering DOI) - 26 Mar 2020
Viewed by 122
Abstract
Coronary artery bypass graft surgery (CABG) might adversely affect the health status of the patients, producing cognitive deterioration, with depression being the most common symptom. The aim of this study is to analyse the prevalence of depression in patients before and after coronary [...] Read more.
Coronary artery bypass graft surgery (CABG) might adversely affect the health status of the patients, producing cognitive deterioration, with depression being the most common symptom. The aim of this study is to analyse the prevalence of depression in patients before and after coronary artery bypass surgery. A systematic review and meta-analysis was carried out, involving a study of the past 10 years of the following databases: CINAHL, LILACS, MEDLINE, PsycINFO, SciELO, Scopus, and Web of Science. The total sample comprised n = 16,501 patients. The total number of items was n = 65, with n = 29 included in the meta-analysis. Based on the different measurement tools used, the prevalence of depression pre-CABG ranges from 19–37%, and post-CABG from 15–33%. There is a considerable presence of depression in this type of patient, but this varies according to the measurement tool used and the quality of the study. Systematically detecting depression prior to cardiac surgery could identify patients at potential risk. Full article
(This article belongs to the Section Epidemiology & Public Health)
Open AccessArticle
The Development of the Ascending Aortic Wall in Tricuspid and Bicuspid Aortic Valve: A Process from Maturation to Degeneration
J. Clin. Med. 2020, 9(4), 908; https://doi.org/10.3390/jcm9040908 (registering DOI) - 26 Mar 2020
Viewed by 114
Abstract
Background: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in the tricuspid aortic valve (TAV) and the BAV populations as a reference for [...] Read more.
Background: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in the tricuspid aortic valve (TAV) and the BAV populations as a reference for future studies on aortopathy and related syndromes. Methods: Non-dilated TAV and BAV ascending aortic wall samples were collected, including 60 TAV (embryonic–70 years) and 32 BAV specimens (fetal–72 years, categorized in eight age groups. Results: In TAV, intimal development starts in the neonatal phase. After birth, the thickness of the medial layer increases significantly by increase of elastic lamellae up to and including the “young child” phase stabilizing afterwards. The BAV shows already prenatal intimal thickening becoming significantly thinner after birth subsequently stabilizing. In BAV, increase in elastic lamellae is seen between the young child and the adolescent phases, stabilizing afterwards. Conclusions: Vascular development in TAV is described in three phases: maturation, stabilization, and degeneration. For BAV, the development can be described in two phases: maturation (already prenatally) and degeneration. After birth, the development of the aorta is characterized by degeneration, leading to weakening of the ascending aortic wall and increasing the risk of aortopathy. Full article
Open AccessArticle
Importance of Footwear Outsole Rigidity in Improving Spatiotemporal Parameters in Patients with Diabetes and Previous Forefoot Ulcerations
J. Clin. Med. 2020, 9(4), 907; https://doi.org/10.3390/jcm9040907 (registering DOI) - 25 Mar 2020
Viewed by 326
Abstract
We aimed to identify if any differences existed in spatiotemporal parameters during gait among different densities of rocker soles in patients with a history of neuropathic ulcerations and the differences in comfort between shoe conditions. This study was a cross-sectional study of 24 [...] Read more.
We aimed to identify if any differences existed in spatiotemporal parameters during gait among different densities of rocker soles in patients with a history of neuropathic ulcerations and the differences in comfort between shoe conditions. This study was a cross-sectional study of 24 patients with diabetes and a history of neuropathic diabetic foot ulcers (DFUs). Spatiotemporal parameters (duration of stance phase (ms), stride length (cm), and step velocity (m/s)) were analyzed in barefoot, semirigid outsole, and rigid outsole footwear conditions. A dynamic pressure measurement system (Footscan® system, RSscan International, Belgium) was used to assess shoe conditions. We also analyzed differences in comfort between the shoe conditions using a visual analog scale. A Wilcoxon test for paired samples was used to assess gait differences. Result showed that a rigid outsole causes changes in the subphases of the stance phase (p < 0.001; Cohen d = 0.6) compared to a semirigid outsole. Stride length (p < 0.001; Cohen d = 0.66) and step velocity were significantly longer (p < 0.001; Cohen d = 2.03) with the use of rigid outsole footwear. A rigid rocker sole reduces the time of the stance phase, in addition to increasing the stride length and velocity of step in patients with a previous history of DFUs. Full article
(This article belongs to the Special Issue Diabetic Foot Complications: Current Challenges and Future Prospects)
Open AccessArticle
Sacubitril/Valsartan Induces Global Cardiac Reverse Remodeling in Long-Lasting Heart Failure with Reduced Ejection Fraction: Standard and Advanced Echocardiographic Evidences
J. Clin. Med. 2020, 9(4), 906; https://doi.org/10.3390/jcm9040906 (registering DOI) - 25 Mar 2020
Viewed by 121
Abstract
Sacubitril/valsartan reduces mortality in heart failure with reduced ejection fraction (HFrEF) patients, partially due to cardiac reverse remodeling (RR). Little is known about the RR rate in long-lasting HFrEF and the evolution of advanced echocardiographic parameters, despite their known prognostic impact in this [...] Read more.
Sacubitril/valsartan reduces mortality in heart failure with reduced ejection fraction (HFrEF) patients, partially due to cardiac reverse remodeling (RR). Little is known about the RR rate in long-lasting HFrEF and the evolution of advanced echocardiographic parameters, despite their known prognostic impact in this setting. We sought to evaluate the rates of left ventricle (LV) and left atrial (LA) RR through standard and advanced echocardiographic imaging in a cohort of HFrEF patients, after the introduction of sacubitril/valsartan. A multi-parametric standard and advanced echocardiographic evaluation was performed at the moment of introduction of sacubitril/valsartan and at 3 to 18 months subsequent follow-up. LVRR was defined as an increase in the LV ejection fraction ≥10 points associated with a decrease ≥10% in indexed LV end-diastolic diameter; LARR was defined as a decrease >15% in the left atrium end-systolic volume. We analyzed 77 patients (65 ± 11 years old, 78% males, 40% ischemic etiology) with 76 (28–165) months since HFrEF diagnosis. After a median follow-up of 9 (interquartile range 6–14) months from the beginning of sacubitril/valsartan, LVRR occurred in 20 patients (26%) and LARR in 33 patients (43%). Moreover, left ventricular global longitudinal strain (LVGLS) improved from −8.3 ± 4% to −12 ± 4.7% (p < 0.001), total left atrial emptying fraction (TLAEF) from 28.2 ± 14.4% to 32.6 ± 13.7% (p = 0.01) and peak atrial longitudinal strain (PALS) from 10.3 ± 6.9% to 13.7 ± 7.6% (p < 0.001). In HFrEF patients, despite a long history of the disease, the introduction of sacubitril/valsartan provides a rapid global (i.e., LV and LA) RR in >25% of cases, both at standard and advanced echocardiographic evaluations. Full article
(This article belongs to the Section Cardiology)
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