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J. Clin. Med., Volume 8, Issue 12 (December 2019)

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Open AccessArticle
Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients
J. Clin. Med. 2019, 8(12), 2197; https://doi.org/10.3390/jcm8122197 (registering DOI) - 12 Dec 2019
Abstract
The liver plays a central role in the glucose and lipid metabolism. Studies performed on animal models have shown an important role of lipid accumulation in the induction of insulin resistance. We sought to explain whether in obese humans, the insulin resistance is [...] Read more.
The liver plays a central role in the glucose and lipid metabolism. Studies performed on animal models have shown an important role of lipid accumulation in the induction of insulin resistance. We sought to explain whether in obese humans, the insulin resistance is associated with hepatic ceramide accumulation. The experiments were conducted on obese men and women. Each gender was divided into three groups: Normal glucose tolerance group (NGT), Impaired glucose tolerance group (IGT), and Type 2 diabetic subjects (T2D). Ceramide (Cer) content was analyzed with the use of LC/MS/MS. An oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1c), percentage body fat (FAT%), and body mass index (BMI) was also measured. Total hepatic ceramide was significantly higher in T2D females as compared to NGT females (p < 0.05), whereas in males, total ceramide was significantly higher in IGT and T2D as compared to NGT (p < 0.05). In both, men and women, the highest increase in T2D subjects, was observed in C16:0-Cer, C18:0:-Cer, C22:0-Cer, and C24:0-Cer (p < 0.05) as compared to NGT group. Interestingly, glucose (at 0′ and at 120′ in OGTT) and HbA1c positively correlated with the ceramide species that most increased in T2D patients (C16:0-Cer, C18:0-Cer, C22:0-Cer, and C24:0-Cer). In men glucose and HbA1c significantly correlated with only C22:0-Cer. This is one of the few studies comparing hepatic ceramide content in severely obese patients. We found that, ceramide content increased in diabetic patients, both in men and women, and the content of ceramide correlated with glycemic parameters. These data indicate ceramide contribution to the induction of hepatic insulin resistance. Full article
(This article belongs to the Section Endocrinology & Metabolism)
Open AccessArticle
Phase I/II Study of Docetaxel and S-1 in Previously-Treated Patients with Advanced Non-Small Cell Lung Cancer: LOGIK0408
J. Clin. Med. 2019, 8(12), 2196; https://doi.org/10.3390/jcm8122196 (registering DOI) - 12 Dec 2019
Abstract
Background: As docetaxel plus S-1 may be feasible for cancer treatment, we conducted a phase I/II trial to determine the recommended docetaxel dose and the fixed S-1 dose (phase I), as well as confirm the regimen’s efficacy and safety (phase II) for previously-treated [...] Read more.
Background: As docetaxel plus S-1 may be feasible for cancer treatment, we conducted a phase I/II trial to determine the recommended docetaxel dose and the fixed S-1 dose (phase I), as well as confirm the regimen’s efficacy and safety (phase II) for previously-treated patients with advanced non-small cell lung cancer. Methods: Patients ≤75 years with performance status ≤1 and adequate organ function were treated at three-week intervals with docetaxel on day 1 and 80 mg/m2 oral S-1 from days 1–14. The starting docetaxel dose was 45 mg/m2 and this was escalated to a maximum of 70 mg/m2. In phase II, response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. Results: The recommended doses were 50 mg/m2 docetaxel (day 1) and 80 mg/m2 S-1 (days 1–14). Grades 3 and 4 leukocytopenia and neutropenia occurred in 44% and 67% of patients, respectively. Nonhematologic toxicities were generally mild. Overall response to chemotherapy was 7.7% (95% confidence interval (CI), 1.6–20.9%), and median PFS and OS were 18.0 weeks (95% CI; 11.3–22.9 weeks) and 53.0 weeks, respectively. Conclusion: Fifty mg/m2 docetaxel plus 80 mg/m2 oral S-1 had a lower response rate than anticipated; however, the survival data were encouraging. A further investigation is warranted to select the optimal patient population. Full article
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Open AccessReview
Metabolic Alterations in Inherited Cardiomyopathies
J. Clin. Med. 2019, 8(12), 2195; https://doi.org/10.3390/jcm8122195 (registering DOI) - 12 Dec 2019
Abstract
The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand [...] Read more.
The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. These genetic diseases are characterized by cardiac structural and functional anomalies in the absence of abnormal conditions that can explain the observed myocardial abnormality, and are frequently associated with heart failure. Since their original description, major advances have been achieved in the genetic and phenotype knowledge, highlighting the involvement of metabolic abnormalities in their pathogenesis. This review provides a brief overview of the role of mitochondria in the energy metabolism in the heart and focuses on metabolic abnormalities, mitochondrial dysfunction, and storage diseases associated with inherited cardiomyopathies. Full article
(This article belongs to the Special Issue The Metabolic Mechanisms of Cardiomyopathy)
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Open AccessArticle
Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism
J. Clin. Med. 2019, 8(12), 2194; https://doi.org/10.3390/jcm8122194 (registering DOI) - 12 Dec 2019
Abstract
Despite findings that aldosterone impairs glucose metabolism, studies concerning the effect of primary aldosteronism (PA) and its treatment on glucose metabolism are controversial. We aimed to determine glucose metabolism in PA and the effect of the treatment modality. We compared glucose metabolism between [...] Read more.
Despite findings that aldosterone impairs glucose metabolism, studies concerning the effect of primary aldosteronism (PA) and its treatment on glucose metabolism are controversial. We aimed to determine glucose metabolism in PA and the effect of the treatment modality. We compared glucose metabolism between PA patients (N = 286) and age-, sex-, and body mass index-matched controls (N = 816), and the changes in glucose metabolism depending on the treatment modality (adrenalectomy vs. spironolactone treatment). Hyperglycemia including diabetes mellitus (DM; 19.6% vs. 13.1%, p = 0.011) was more frequent in PA patients. Hyperglycemia was also more frequent in PA patients without subclinical hypercortisolism (SH: p < 0.001) and in those regardless of hypokalemia (p < 0.001–0.001). PA patients and PA patients without SH had higher DM risk (odds ratio (OR); 95% confidence interval (CI): 1.63; 1.11–2.39 and 1.65; 1.08–2.51, respectively) after adjusting confounders. In PA patients, there was significant decrease in the DM prevalence (21.3% to 16.7%, p = 0.004) and fasting plasma glucose (p = 0.006) after adrenalectomy. However, there was no significant change in them after spironolactone treatment. Adrenalectomy was associated with more improved glucose status than spironolactone treatment (OR; 95% CI: 2.07; 1.10–3.90). Glucose metabolism was impaired in PA, regardless of hypokalemia and SH status, and was improved by adrenalectomy, but not spironolactone treatment. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessEditorial
Comments from the Editor of the Special Issue “Clinical Research on Diabetic Complications”
J. Clin. Med. 2019, 8(12), 2193; https://doi.org/10.3390/jcm8122193 (registering DOI) - 12 Dec 2019
Abstract
With this Editorial, we are hereby presenting to the reader the Special Issue on “Clinical Research on Diabetic Complications”. Chronic complications of diabetes mellitus have a major impact on the life of subjects with the disease, resulting in decreased quality of life and [...] Read more.
With this Editorial, we are hereby presenting to the reader the Special Issue on “Clinical Research on Diabetic Complications”. Chronic complications of diabetes mellitus have a major impact on the life of subjects with the disease, resulting in decreased quality of life and increased morbidity and mortality. This Special Issue includes contributions addressing different clinical aspects of the natural history, prevention and prediction, and characterization and management of diabetes-related complications. Full article
(This article belongs to the Special Issue Clinical Research on Diabetic Complications)
Open AccessArticle
High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study
J. Clin. Med. 2019, 8(12), 2192; https://doi.org/10.3390/jcm8122192 (registering DOI) - 12 Dec 2019
Abstract
Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was [...] Read more.
Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome. Full article
(This article belongs to the Special Issue Therapies for Myocardial Injury and Infarction)
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Open AccessArticle
Reference Values for Cardiorespiratory Fitness in Healthy Koreans
J. Clin. Med. 2019, 8(12), 2191; https://doi.org/10.3390/jcm8122191 (registering DOI) - 12 Dec 2019
Abstract
We investigated reference values for cardiorespiratory fitness (CRF) for healthy Koreans and Koreans with coronary heart disease (CHD) and used them to identify inter-ethnic differences in CRF, differences over time in CRF, and differences in CRF between the healthy population and patients with [...] Read more.
We investigated reference values for cardiorespiratory fitness (CRF) for healthy Koreans and Koreans with coronary heart disease (CHD) and used them to identify inter-ethnic differences in CRF, differences over time in CRF, and differences in CRF between the healthy population and patients with CHD. The study population for healthy Koreans was derived from the database of KISS FitS (Korea Institute of Sports Science Fitness Standards) between 2014 and 2015. The study population for Koreans with CHD was derived from the database of the Korea University Guro Hospital Cardiac Rehabilitation Registry between June 2015 and December 2018. In healthy Koreans, there was a significant difference between sex and age groups for VO2 max. The VO2 max of healthy Koreans differed from that of Westerners in age-related reference values. Our results were not significantly different from those of the Korean population in the past, except for a small decline in the young population. There seemed to be a clear inter-ethnic difference in CRF. We could also identify signs of small change in CRF in younger age groups. Therefore, CRF should be assessed according to ethnic or national standards, and it will be necessary to establish a reference for each nation or ethnicity with periodic updates. Full article
(This article belongs to the Special Issue Cardiovascular Rehabilitation)
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Open AccessArticle
Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders
J. Clin. Med. 2019, 8(12), 2190; https://doi.org/10.3390/jcm8122190 (registering DOI) - 12 Dec 2019
Viewed by 37
Abstract
Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes. Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative [...] Read more.
Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes. Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans. Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome. Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct. Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans. However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery. Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway. Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif. Full article
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Open AccessArticle
Management of Immunosuppression in Kidney Transplant Recipients Who Develop Malignancy
J. Clin. Med. 2019, 8(12), 2189; https://doi.org/10.3390/jcm8122189 - 11 Dec 2019
Viewed by 119
Abstract
The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the [...] Read more.
The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85–4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21–4.35, p = 0.01). IS reduction was not statistically associated with worsening graft function (OR 3.8, 95%CI 0.77–18.71, p = 0.10), nor with graft survival (SHR 4.46, 95%CI 0.58–34.48, p = 0.15) after variables adjustment. Creatinine at cancer diagnosis and history of rejection were both negatively associated with graft survival (SHR 1.72, 95%CI 1.28–2.30, p < 0.01 and SHR 3.44, 95%CI 1.25–9.49, p = 0.02). Reduction of both mycophenolate and calcineurin inhibitors was associated with worsening graft function and lower graft survival in subgroup analysis (OR 6.14, 95%CI 1.14–33.15, p = 0.04; HR 17.97, 95%CI 1.81–178.78, p = 0.01). In summary, cancer causes high mortality and morbidity in kidney transplant recipients; the importance of cancer screening should be emphasized. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
Open AccessArticle
Dose-Ranging Study of Ramosetron for the Prevention of Nausea and Vomiting after Laparoscopic Gynecological Surgery: A Prospective Randomized Study
J. Clin. Med. 2019, 8(12), 2188; https://doi.org/10.3390/jcm8122188 - 11 Dec 2019
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Abstract
Patients undergoing laparoscopic gynecologic surgery and receiving postoperative analgesia with opioids have a high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of three doses of ramosetron in this high-risk population. In this prospective, double-blind trial, 174 patients randomly [...] Read more.
Patients undergoing laparoscopic gynecologic surgery and receiving postoperative analgesia with opioids have a high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of three doses of ramosetron in this high-risk population. In this prospective, double-blind trial, 174 patients randomly received ramosetron 0.3 mg (R0.3 group; n = 58), 0.45 mg (R0.45 group; n = 58), or 0.6 mg (R0.6 group; n = 58) at the end of surgery. The primary outcome was the incidence of PONV during the first postoperative 48 h. Nausea severity, pain scores, adverse events, and patient satisfaction (1–4; 4, excellent) were assessed. The incidence of PONV was not different between groups (35%, 38%, and 35% in R0.3, R0.45, and R0.6 groups; p = 0.905). Nausea severity, pain scores, and incidence of adverse events (dizziness, headache, or sedation) were similar between groups. Compared to the R0.3 group, the R0.45 and R0.6 groups had lower incidence of premature discontinuation of fentanyl-based patient-controlled analgesia primarily because of intractable PONV (9% and 5% vs. 24%; p = 0.038), and higher satisfaction scores (3.4 ± 0.8 and 3.3 ± 0.7 vs. 2.4 ± 0.9; p = 0.005). Compared to ramosetron 0.3 mg, ramosetron 0.45 and 0.6 mg did not reduce PONV, but reduced premature discontinuation of patient-controlled analgesia and increased patient satisfaction, without increasing adverse events. Full article
(This article belongs to the Section Anesthesiology)
Open AccessArticle
Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis
J. Clin. Med. 2019, 8(12), 2187; https://doi.org/10.3390/jcm8122187 - 11 Dec 2019
Viewed by 119
Abstract
Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) [...] Read more.
Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan–Meier curves and logistic regression analysis. Results: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35−37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26−37.27; p = 0.03). Conclusion: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted. Full article
Open AccessArticle
Exercise Training Enhances Platelet Mitochondrial Bioenergetics in Stroke Patients: A Randomized Controlled Trial
J. Clin. Med. 2019, 8(12), 2186; https://doi.org/10.3390/jcm8122186 - 11 Dec 2019
Viewed by 102
Abstract
Exercise training (ET) may impact physical fitness by affecting mitochondrial functions. This study aimed to elucidate the effect of ET on aerobic capacity and platelet mitochondrial bioenergetics (MTB) in stroke patients. Among the 30 stroke patients who underwent the traditional rehabilitation program (TRP), [...] Read more.
Exercise training (ET) may impact physical fitness by affecting mitochondrial functions. This study aimed to elucidate the effect of ET on aerobic capacity and platelet mitochondrial bioenergetics (MTB) in stroke patients. Among the 30 stroke patients who underwent the traditional rehabilitation program (TRP), 15 were randomly assigned to have ET (50–60% VO2peak for 30 min/day, 5 days/week for 4 weeks), and those remaining received only the TRP (control group). The peak exercise capacity (VO2peak) and platelet MTB, including oxidative phosphorylation (OXPHOS) and the electron transport chain (ETC), were measured through automatic gas analysis and high-resolution respirometry, respectively. The results demonstrated that ET significantly increased the VO2peak (17.7%) and O2 uptake efficiency slope (31.9%) but decreased the ventilation versus CO2 production slope (−7.65%). Patients who underwent ET also had significantly enhanced platelet mitochondrial OXPHOS and ETC by activating the FADH2 (Complex II)-dependent pathway, but depressed plasma myeloperoxidase (−28.4%) and interleukin-6 levels (−29.9%). Moreover, changes in VO2peak levels were positively correlated with changes in platelet OXPHOS and ETC capacities. In conclusion, ET increases the platelet MTB by enhancing Complex II activity in stroke patients. The exercise regimen also enhances aerobic fitness and depresses oxidative stress/pro-inflammatory status in stroke patients. Full article
(This article belongs to the Section Clinical Cytology)
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Open AccessArticle
One-Stop Management of 230 Consecutive Acute Stroke Patients: Report of Procedural Times and Clinical Outcome
J. Clin. Med. 2019, 8(12), 2185; https://doi.org/10.3390/jcm8122185 - 11 Dec 2019
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Abstract
Background and purpose: Rapid thrombectomy for acute ischemic stroke caused by large vessel occlusion leads to improved outcome. Optimizing intrahospital management might diminish treatment delays. To examine if one-stop management reduces intrahospital treatment delays and improves functional outcome of acute stroke patients with [...] Read more.
Background and purpose: Rapid thrombectomy for acute ischemic stroke caused by large vessel occlusion leads to improved outcome. Optimizing intrahospital management might diminish treatment delays. To examine if one-stop management reduces intrahospital treatment delays and improves functional outcome of acute stroke patients with large vessel occlusion. Methods: We performed a single center, observational study from June 2016 to November 2018. Imaging was acquired with the latest generation angiography suite at a comprehensive stroke center. Two-hundred-thirty consecutive adults with suspected acute stroke presenting within 6 h after symptom onset with a moderate to severe National Institutes of Health Stroke Scale (≥10 in 2016; ≥7 since January 2017) were directly transported to the angiography suite by bypassing multidetector CT. Noncontrast flat-detector CT and biphasic flat-detector CT angiography were acquired with an angiography system. In case of a large vessel occlusion patients remained in the angiography suite, received intravenous rtPA therapy and underwent thrombectomy. As primary endpoints, door-to-reperfusion times and functional outcome at 90 days were recorded and compared in a case-control analysis with matched prior patients receiving standard management. Results: A total of 230 patients (123 women, median age of 78 years (Interquartile Range (IQR) 69–84)) were included. Median symptom-to-door time was 130 min (IQR 70–195). Large vessel occlusion was diagnosed in 166/230 (72%) patients; 64/230 (28%) had conditions not suitable for thrombectomy. Median door-to-reperfusion time for M1 occlusions was 64 min (IQR 56–87). Compared to 43 case-matched patients triaged with multidetector CT, median door-to-reperfusion time was reduced from 102 (IQR 85–117) to 68 min (IQR 53–89; p < 0.001). Rate of good functional outcome was significantly better in the one-stop management group (p = 0.029). Safety parameters (mortality, sICH, any hemorrhage) did not differ significantly between groups. Conclusions: One-stop management for stroke triage reduces intrahospital time delays in our specific hospital setting. Full article
(This article belongs to the Special Issue Diagnosis, Prevention and Treatment for Stroke)
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Open AccessArticle
A Humanized Bone Niche Model Reveals Bone Tissue Preservation Upon Targeting Mitochondrial Complex I in Pseudo-Orthotopic Osteosarcoma
J. Clin. Med. 2019, 8(12), 2184; https://doi.org/10.3390/jcm8122184 - 11 Dec 2019
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Abstract
A cogent issue in cancer research is how to account for the effects of tumor microenvironment (TME) on the response to therapy, warranting the need to adopt adequate in vitro and in vivo models. This is particularly relevant in the development of strategies [...] Read more.
A cogent issue in cancer research is how to account for the effects of tumor microenvironment (TME) on the response to therapy, warranting the need to adopt adequate in vitro and in vivo models. This is particularly relevant in the development of strategies targeting cancer metabolism, as they will inevitably have systemic effects. For example, inhibition of mitochondrial complex I (CI), despite showing promising results as an anticancer approach, triggers TME-mediated survival mechanisms in subcutaneous osteosarcoma xenografts, a response that may vary according to whether the tumors are induced via subcutaneous injection or by intrabone orthotopic transplantation. Thus, with the aim to characterize the TME of CI-deficient tumors in a model that more faithfully represents osteosarcoma development, we set up a humanized bone niche ectopic graft. A prominent involvement of TME was revealed in CI-deficient tumors, characterized by the abundance of cancer associated fibroblasts, tumor associated macrophages and preservation of osteocytes and osteoblasts in the mineralized bone matrix. The pseudo-orthotopic approach allowed investigation of osteosarcoma progression in a bone-like microenvironment setting, without being invasive as the intrabone cell transplantation. Additionally, establishing osteosarcomas in a humanized bone niche model identified a peculiar association between targeting CI and bone tissue preservation. Full article
(This article belongs to the Special Issue The Rise of Mitochondria in Medicine)
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Open AccessArticle
Influence of Biologically Oriented Preparation Technique on Peri-Implant Tissues; Prospective Randomized Clinical Trial with Three-Year Follow-Up. Part I: Hard Tissues
J. Clin. Med. 2019, 8(12), 2183; https://doi.org/10.3390/jcm8122183 - 11 Dec 2019
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Abstract
Purpose: The objective of this prospective randomized clinical trial (RCT) was to analyze and compare the clinical behavior of three types of prosthesis supported by single implants in the posterior region after three years functional loading. Materials and Methods: Seventy-five implants were divided [...] Read more.
Purpose: The objective of this prospective randomized clinical trial (RCT) was to analyze and compare the clinical behavior of three types of prosthesis supported by single implants in the posterior region after three years functional loading. Materials and Methods: Seventy-five implants were divided into three groups according to the type of prosthetic restoration: screw-retained crown (Group GS); cemented crown without finishing line (biologically oriented preparation technique) (Group GBOPT); and conventional cemented crown with finishing line (Group GCC). The clinical behavior of each restoration type was analyzed after 3 years functional loading by analyzing radiographic peri-implant bone loss. Results: GBOPT obtained the least bone loss (p < 0.01) in comparison with GS and GCC. Conclusions: Bone loss around implants is related to the type of prosthetic restoration it supports, whereby cemented BOPT crowns present less bone loss. Full article
(This article belongs to the Special Issue Implant Dentistry—Trends, Challenges and Innovations)
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Open AccessArticle
Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis
J. Clin. Med. 2019, 8(12), 2182; https://doi.org/10.3390/jcm8122182 - 11 Dec 2019
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Abstract
Gonorrhea is the second most frequently reported sexually transmitted infectious disease of bacterial origin in the world. Current empiric therapies rely on broad-spectrum antibiotics. However, treatment options are becoming limited due to the rise of drug-resistant gonorrhea. To control the rise of drug-resistant [...] Read more.
Gonorrhea is the second most frequently reported sexually transmitted infectious disease of bacterial origin in the world. Current empiric therapies rely on broad-spectrum antibiotics. However, treatment options are becoming limited due to the rise of drug-resistant gonorrhea. To control the rise of drug-resistant gonorrhea and to identify alternative treatment options, clinicians will have to increasingly rely on experimental evidence for the treatment of gonorrhea patients. Thus, we performed a systematic review and network meta-analysis of all randomized clinical trials about the efficacy and safety of various antibiotic regimens in adults with gonorrhea. We searched all references in Embase and PubMed from the date of their inception to January 2019, and then an updated search was performed in March 2019. Of the 28,843 identified references, 44 fulfilled our selection criteria. We used a network meta-analysis based on a frequentist approach to evaluate the efficacy and safety of 12 injectable and 11 oral antibiotics. The efficacy of treatments was ranked by p score and inconsistency was assessed by a back-calculation method. Certainty of evidence was evaluated by the GRADE system. For injectable drugs, there was no difference in efficacy between a reference antibiotic and other drugs. However, ceftriaxone had significantly better efficacy than cefuroxime (OR, 12.03; 95% CI 3.73–38.79), cephaloridine (OR, 42.41; 95% CI 8.77–205.07), kanamycin (OR, 5.45; 95% CI 1.25–23.70), penicillin (OR, 13.11; 95% CI 4.48–38.37), and spectinomycin (OR, 4.70; 95% CI 1.62–13.62). Thus, ceftriaxone was the most effective injectable drug (p score of 0.924). As for oral drugs, azithromycin was the most effective compound (p score of 0.8633). There were no significant differences in safety between injectable and oral treatments. In our systematic review of randomized controlled trials, we found azithromycin and ceftriaxone to be the most effective antibiotics for the treatment of gonorrhea. This is in line with current guidelines which recommend a combination therapy of azithromycin and ceftriaxone for the treatment of gonorrhea due to increased antimicrobial resistance. Our analysis identified gentamicin and ofloxacin as alternative therapeutics to treat drug-resistant gonorrhea. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessArticle
Retinal Microperimetry: A Useful Tool for Detecting Insulin Resistance-Related Cognitive Impairment in Morbid Obesity
J. Clin. Med. 2019, 8(12), 2181; https://doi.org/10.3390/jcm8122181 - 11 Dec 2019
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Abstract
Background: There is clear association between type 2 diabetes (T2D) and cognitive decline. Retinal microperimetry is a useful tool for detecting cognitive impairment in T2D. Morbid obesity (MO) has been associated with cognitive impairment. Insulin resistance (IR) seems a major determinant, but the [...] Read more.
Background: There is clear association between type 2 diabetes (T2D) and cognitive decline. Retinal microperimetry is a useful tool for detecting cognitive impairment in T2D. Morbid obesity (MO) has been associated with cognitive impairment. Insulin resistance (IR) seems a major determinant, but the data are unclear. The aim of this study was to evaluate the cognitive impairment in MO as well as the utility of retinal microperimetry in identifying these alterations. Methods: In total, 50 consecutive patients with MO were matched by age and gender with 30 healthy controls. All patients underwent cognitive evaluation (Montreal Cognitive Assessment Test-MoCA) and retinal microperimetry, using MAIA microperimeter 3rd generation. Retinal sensitivity and gaze fixation parameters were used for the evaluation of the analysis. Results: MO patients showed a significantly lower neurocognitive performance than the controls: MoCA score 24.94 ± 2.74 vs. 28.95 ± 1.05, p < 0.001. Cognitive function inversely correlated with the HOMA-IR (r = −0.402, p = 0.007). The AUROC for cognitive impairment using microperimetry was 0.807, CI 95% (0.592–0.947), p = 0.017. Conclusions: (1) Systemic insulin resistance is a major underlying mechanism accounting for the higher prevalence of cognitive impairment detected in young MO subjects. (2) Retinal microperimetry is a useful tool for identifying MO patients with cognitive impairment. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessCommunication
Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer
J. Clin. Med. 2019, 8(12), 2180; https://doi.org/10.3390/jcm8122180 - 11 Dec 2019
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Abstract
The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC [...] Read more.
The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (≥20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle
Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population
J. Clin. Med. 2019, 8(12), 2179; https://doi.org/10.3390/jcm8122179 - 11 Dec 2019
Viewed by 126
Abstract
The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue [...] Read more.
The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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Open AccessArticle
Prevalence, Risk Factors and Course of Osteoporosis in Patients with Crohn’s Disease at a Tertiary Referral Center
J. Clin. Med. 2019, 8(12), 2178; https://doi.org/10.3390/jcm8122178 - 10 Dec 2019
Viewed by 157
Abstract
Background: Patients with Crohn’s disease are at increased risk for fractures due to low bone mineral density (BMD). Real-world data are necessary to optimize surveillance and treatment strategies. Methods: Patients with Crohn’s disease who underwent at least one dual-energy X-ray absorptiometry (DXA) scans [...] Read more.
Background: Patients with Crohn’s disease are at increased risk for fractures due to low bone mineral density (BMD). Real-world data are necessary to optimize surveillance and treatment strategies. Methods: Patients with Crohn’s disease who underwent at least one dual-energy X-ray absorptiometry (DXA) scans were recruited. The primary study endpoints were (1) prevalence of osteoporosis, and (2) factors influencing changes of BMD. To identify potential risk factors for reduced BMD, Mann–Whitney U-test was used for ordinal and continuous variables and x²-tests for categorical variables. Results with p < 0.05 were included in a multivariable analysis. To identify potential factors influencing changes in BMD, a generalized linear mixed model was applied. Results: 39.9% of the patients were diagnosed with normal BMD, 40.2% with osteopenia, and 19.8% with osteoporosis. The main risk factors for osteoporosis were low body mass index (BMI), previous bowel resections and male sex. The main risk factors for reduced BMD during further along the disease course were steroid use, history of immunomodulator treatment, female sex and decreased BMI. Conclusion: Low BMI, previous bowel resections and male sex were the main risk factors for the development of osteoporosis. Steroid use reduced BMD even under anti-inflammatory therapy, underlining that they should be used with great care in that patient group. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
Open AccessArticle
Structured Cognitive-Motor Dual Task Training Compared to Single Mobility Training in Persons with Multiple Sclerosis, a Multicenter RCT
J. Clin. Med. 2019, 8(12), 2177; https://doi.org/10.3390/jcm8122177 - 10 Dec 2019
Viewed by 138
Abstract
The aim was to compare the effectiveness of dual-task training (DTT) compared to single mobility training (SMT) on dual-task walking, mobility and cognition, in persons with Multiple Sclerosis (pwMS). Forty pwMS were randomly assigned to the DTT or SMT groups. The DTT-group performed [...] Read more.
The aim was to compare the effectiveness of dual-task training (DTT) compared to single mobility training (SMT) on dual-task walking, mobility and cognition, in persons with Multiple Sclerosis (pwMS). Forty pwMS were randomly assigned to the DTT or SMT groups. The DTT-group performed dual-task exercises using an interactive tablet-based application, while the SMT-group received conventional walking and balance exercises. Both interventions were supervised and identical in weeks (8) and sessions (20). Nine cognitive-motor dual-task conditions were assessed at baseline, after intervention and at 4-weeks follow-up (FU). The dual-task cost (DTC), percentage change of dual-task performance compared to single-task performance, was the primary outcome. Mobility and cognition were secondarily assessed. Mixed model analyses were done with group, time and the interaction between group and time as fixed factors and participants as random factors. Significant time by group interactions were found for the digit-span walk and subtraction walk dual-task conditions, with a reduction in DTC (gait speed) for the DTT maintained at FU. Further, absolute dual-task gait speed during walking over obstacles only improved after the DTT. Significant improvements were found for both groups in various motor and cognitive measures. However, the DTT led to better dual-task walking compared to the SMT. Full article
(This article belongs to the Section Clinical Neurology)
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Open AccessArticle
Impact of Antiplatelet Therapies on Patients Outcome in Osteosynthetic Surgery of Proximal Femoral Fractures
J. Clin. Med. 2019, 8(12), 2176; https://doi.org/10.3390/jcm8122176 - 09 Dec 2019
Viewed by 188
Abstract
Background: Proximal femoral fractures should be treated in a timely manner. Affected patients often require antiplatelet therapy (APT) due to cardiovascular diseases. Guidelines recommend 5-7 days APT interruption for elective surgery. Early osteosynthetic surgery of proximal femoral fractures despite of APT should be [...] Read more.
Background: Proximal femoral fractures should be treated in a timely manner. Affected patients often require antiplatelet therapy (APT) due to cardiovascular diseases. Guidelines recommend 5-7 days APT interruption for elective surgery. Early osteosynthetic surgery of proximal femoral fractures despite of APT should be considered. Aim of the study: To evaluate whether early osteosynthetic surgery despite of APT is associated with increased blood loss, complications and mortality. Methods: Data of patients with proximal femoral fractures, who were treated by osteosynthesis at the Department of Trauma Surgery at the Medical University of Vienna were collected retrospectively. Study groups were formed by time to surgery and APT interruption. The primary endpoint of the study was the perioperative blood loss. Secondary endpoints were complications, 30-day and 1-year mortality, time to surgery, and the total length of hospital stay. Results: The osteosynthetic treatment of proximal femoral fractures despite of APT resulted in a shorter time to surgery (13.8 vs. 66.0 h; p < 0.01). In patients on APT, the TBL (total perioperative blood loss) was higher without need for revision or an increase in the need for packed red blood cells if surgery was performed within 24 h after admission. APT had no significant influence on mortality. Patients who underwent surgery within 24 h after admission had a lower mortality. The complication rate was higher in patients who underwent surgery later than 24 h after admission. Conclusions: Surgery within 24 h after admission, regardless of APT, resulted in a shorter hospitalization length and was associated with less common complications and a lower mortality. Full article
(This article belongs to the Section Orthopedics)
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Open AccessArticle
Reduction of Fat to Muscle Mass Ratio Is Associated with Improvement of Liver Stiffness in Diabetic Patients with Non-Alcoholic Fatty Liver Disease
J. Clin. Med. 2019, 8(12), 2175; https://doi.org/10.3390/jcm8122175 - 09 Dec 2019
Viewed by 170
Abstract
Body weight reduction leads to improvement of nonalcoholic fatty liver disease (NAFLD), but the contributions of body composition modification on its improvement have not been clarified yet. We performed a retrospective cohort study in a Japanese university hospital to clarify the effect of [...] Read more.
Body weight reduction leads to improvement of nonalcoholic fatty liver disease (NAFLD), but the contributions of body composition modification on its improvement have not been clarified yet. We performed a retrospective cohort study in a Japanese university hospital to clarify the effect of body fat reduction on the improvement of hepatic stiffness as well as hepatic steatosis. The skeletal muscle mass index (SMI, kg/m2), fat to muscle mass ratio, and the change in fat to muscle mass ratio after 1 year from baseline were calculated. Controlled attenuation parameter (CAP, dB/m) and liver stiffness measurement (LSM, kPa) were evaluated by elastography. Primary outcome was set as the association of the change of fat to muscle mass ratio after 1 year from baseline with the change of liver stiffness measurement. One hundred and seventeen patients (59 men and 58 women) completed the study. The average age was 63.5 years, and baseline CAP and LSM were 273.4 ± 53.5 dB/m and 6.3 ± 3.4 kPa, respectively. After 1 year, body mass index (BMI), SMI, and LSM decreased. Multiple regression analyses demonstrated that change in fat to muscle mass ratio was associated with the change in CAP (ß = 0.38, p < 0.001) or LSM (ß = 0.21, p = 0.026). The reduction of fat to muscle mass ratio was associated with improvement in liver stiffness, but the reduction of BMI was not. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessArticle
Pseudoerosions of Hands and Feet in Rheumatoid Arthritis: Anatomic Concepts and Redefinition
J. Clin. Med. 2019, 8(12), 2174; https://doi.org/10.3390/jcm8122174 - 09 Dec 2019
Viewed by 149
Abstract
Rheumatoid arthritis is a chronic inflammatory disease characterized by the development of osseous and cartilaginous damage. The correct differentiation between a true erosion and other entities—then often called “pseudoerosions”—is essential to avoid misdiagnosing rheumatoid arthritis and to correctly interpret the progress of the [...] Read more.
Rheumatoid arthritis is a chronic inflammatory disease characterized by the development of osseous and cartilaginous damage. The correct differentiation between a true erosion and other entities—then often called “pseudoerosions”—is essential to avoid misdiagnosing rheumatoid arthritis and to correctly interpret the progress of the disease. The aims of this systematic review were as follows: to create a definition and delineation of the term “pseudoerosion”, to point out morphological pitfalls in the interpretation of images, and to report on difficulties arising from choosing different imaging modalities. A systematic review on bone erosions in rheumatoid arthritis was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following search terms were applied in PubMed and Scopus: “rheumatoid arthritis”, “bone erosion”, “ultrasonography”, “radiography”, “computed tomography” and “magnetic resonance imaging”. Appropriate exclusion criteria were defined. The systematic review registration number is 138826. The search resulted ultimately in a final number of 25 papers. All indications for morphological pitfalls and difficulties utilizing imaging modalities were recorded and summarized. A pseudoerosion is more than just a negative definition of an erosion; it can be anatomic (e.g., a normal osseous concavity) or artefact-related (i.e., an artificial interruption of the calcified zones). It can be classified according to their configuration, shape, content, and can be described specifically with an anatomical term. “Calcified zone” is a term to describe the deep components of the subchondral, subligamentous and subtendinous bone, and may be applied for all non-cancellous borders of a bone, thus representing a third type of the bone matrix beside the cortical and the trabecular bone. Full article
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Open AccessArticle
Comparison between Adult Patients with Sickle Cell Disease of Sub-Saharan African Origin Born in Metropolitan France and in Sub-Saharan Africa
J. Clin. Med. 2019, 8(12), 2173; https://doi.org/10.3390/jcm8122173 - 09 Dec 2019
Viewed by 149
Abstract
Sickle cell disease (SCD) prevalence has increased rapidly in Europe as a result of an increase in the life expectancy of these patients and the arrival of SCD migrants from Africa. The aim of our study was to compare the phenotypes of adult [...] Read more.
Sickle cell disease (SCD) prevalence has increased rapidly in Europe as a result of an increase in the life expectancy of these patients and the arrival of SCD migrants from Africa. The aim of our study was to compare the phenotypes of adult patients born in Sub-Saharan Africa (SSA) who migrated to France with those of patients with the same origin who were born in France. This single-center observational study compared the demographic, clinical and biological characteristics of SCD adult patients of SSA origin who were born in France or SSA. Data were collected from computerized medical charts. Groups were compared using multivariate logistic regression with adjustment for age, gender and type of SCD. Of the 323 SCD patients followed in our center, 235 were enrolled, including 111 patients born in France and 124 patients born in SSA. SCD genotypes were balanced between groups. Patients born in Africa were older (median age 32.1 (24.4–39) vs. 25.6 (22.1–30.5) years, p < 0.001) and more often women (n = 75 (60.5%) vs. 48 (43.2%), p = 0.008). The median age at arrival in France was 18 years (13–23). The median height was lower among patients born in SSA (169 (163–175) vs. 174.5 cm (168–179), p < 0.001). Over their lifetimes, patients born in France had more acute chest syndromes (median number 2 (1–4) vs. 1 (0–3), p = 0.002), with the first episode occurring earlier (19 (11.6–22.3) vs. 24 (18.4–29.5) years, p < 0.007), and were admitted to intensive care units more often (53.3% vs. 34.9%, p = 0.006). This difference was more pronounced in the SS/Sβ0 population. Conversely, patients born in SSA had more skin ulcers (19.4% vs. 6.3%, p = 0.03). No significant differences were found in social and occupational insertion or other complications between the two groups. Patients born in SSA had a less severe disease phenotype regardless of their age than those born in France. This difference could be related to a survival bias occurring in Africa during childhood and migration to Europe that selected the least severe phenotypes. Full article
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Open AccessArticle
Clinical and Ultrasound Thyroid Nodule Characteristics and Their Association with Cytological and Histopathological Outcomes: A Retrospective Multicenter Study in High-Resolution Thyroid Nodule Clinics
J. Clin. Med. 2019, 8(12), 2172; https://doi.org/10.3390/jcm8122172 - 09 Dec 2019
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Abstract
Introduction: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. Design and Methods: A retrospective cross-sectional multicenter [...] Read more.
Introduction: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. Design and Methods: A retrospective cross-sectional multicenter study including data from four HR-TNCs in Spain. We evaluated fine-needle aspiration (FNA) indications and the association between clinical and ultrasound characteristics with cytological and histopathological outcomes. Results: A total of 2809 thyroid nodules were included; FNA was performed in 82.1%. Thyroid nodules that underwent FNA were more likely larger, isoechoic, with microcalcifications, and in younger subjects. The rate of nondiagnostic FNA was 4.3%. A solid component, irregular margins or microcalcifications, significantly increased the odds of Bethesda IV-V-VI (vs. Bethesda II). Irregular margins and a solid component were independently associated with increased odds of malignancy. Thyroid nodules <20 mm and ≥20–<40 mm had a 6.5-fold and 3.3-fold increased risk for malignancy respectively in comparison with those ≥40 mm. Conclusion: In this large multicenter study, we found that the presence of a solid component and irregular margins are factors independently related to malignancy in thyroid nodules. Since nodule size ≥40 mm was associated with the lowest odds of malignancy, this cut-off should not be a factor leading to indicate thyroid surgery. HR-TNCs were associated with a low rate of nondiagnostic FNA. Full article
(This article belongs to the Special Issue Imaging and Imaging-Based Management of Thyroid Nodules)
Open AccessEditorial
Acute Respiratory Distress Syndrome (ARDS): Pathophysiological Insights and Lung Imaging
J. Clin. Med. 2019, 8(12), 2171; https://doi.org/10.3390/jcm8122171 - 09 Dec 2019
Viewed by 182
Abstract
Acute respiratory distress syndrome (ARDS) is in the center of the scientific debate both for its complex pathophysiology and for the discussion about the remedies that could contribute to its healing. The intricate interplay of different body systems that characterizes ARDS is mirrored [...] Read more.
Acute respiratory distress syndrome (ARDS) is in the center of the scientific debate both for its complex pathophysiology and for the discussion about the remedies that could contribute to its healing. The intricate interplay of different body systems that characterizes ARDS is mirrored by two main research threads, one centered on the pathophysiological mechanisms of the disease and the other on the new approaches to lung imaging. In this Special Issue of the Journal of Clinical Medicine are presented studies using imaging technologies based on electrical impedance tomography, synchrotron radiation computed tomography and intravital probe-based confocal laser endomicroscopy. The studies on the pathophysiological mechanisms pertain to the evaluation of the biomarkers of the disease and the platelet disfunction during extracorporeal membrane oxygenation. These contributions witness the intensity of ARDS research as many of the key problems of the disease are only in part resolved. Full article
Open AccessReview
Synaptic Pruning by Microglia in Epilepsy
J. Clin. Med. 2019, 8(12), 2170; https://doi.org/10.3390/jcm8122170 - 09 Dec 2019
Viewed by 185
Abstract
Structural and functional collapse of the balance between excitatory (E) and inhibitory (I) synapses, i.e., synaptic E/I balance, underlies the pathogeneses of various central nervous system (CNS) disorders. In epilepsy, the synaptic E/I balance tips toward excitation; thus, most of the existing epileptic [...] Read more.
Structural and functional collapse of the balance between excitatory (E) and inhibitory (I) synapses, i.e., synaptic E/I balance, underlies the pathogeneses of various central nervous system (CNS) disorders. In epilepsy, the synaptic E/I balance tips toward excitation; thus, most of the existing epileptic remedies have focused on how to directly suppress the activity of neurons. However, because as many as 30% of patients with epilepsy are drug resistant, the discovery of new therapeutic targets is strongly desired. Recently, the roles of glial cells in epilepsy have gained attention because glial cells manipulate synaptic structures and functions in addition to supporting neuronal survival and growth. Among glial cells, microglia, which are brain-resident immune cells, have been shown to mediate inflammation, neuronal death and aberrant neurogenesis after epileptic seizures. However, few studies have investigated the involvement of synaptic pruning—one of the most important roles of microglia—in the epileptic brain. In this review, we propose and discuss the hypothesis that synaptic pruning by microglia is enhanced in the epileptic brain, drawing upon the findings of previous studies. We further discuss the possibility that aberrant synaptic pruning by microglia induces synaptic E/I imbalance, promoting the development and aggravation of epilepsy. Full article
(This article belongs to the Special Issue Glial Cells in Central Nervous System (CNS) Pathology and Repair)
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Open AccessReview
Management of Acute Severe Colitis in the Era of Biologicals and Small Molecules
J. Clin. Med. 2019, 8(12), 2169; https://doi.org/10.3390/jcm8122169 - 08 Dec 2019
Viewed by 218
Abstract
Acute severe ulcerative colitis (ASUC) is a medical emergency which occurs in about 20%–30% of patients with ulcerative colitis during their lifetime, and does carry a mortality risk of 1%. The management of inflammatory bowel diseases has evolved with changes in objective patient [...] Read more.
Acute severe ulcerative colitis (ASUC) is a medical emergency which occurs in about 20%–30% of patients with ulcerative colitis during their lifetime, and does carry a mortality risk of 1%. The management of inflammatory bowel diseases has evolved with changes in objective patient monitoring, as well as the availability of new treatment options with the development of new biological and small molecules; however, data is limited regarding their use in the context of ASUC. This review aims to discuss the emerging data regarding biologicals and small molecules therapies in the context of ASUC. Full article
(This article belongs to the Special Issue Ulcerative Colitis: Current and Emerging Treatment Strategies)
Open AccessReview
Basis of PD1/PD-L1 Therapies
J. Clin. Med. 2019, 8(12), 2168; https://doi.org/10.3390/jcm8122168 - 08 Dec 2019
Viewed by 232
Abstract
It is obvious that tumor cells have developed a number of strategies to escape immune surveillance including an altered expression of various immune checkpoints, such as the programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2. The interaction between PD-1 and PD-L1 [...] Read more.
It is obvious that tumor cells have developed a number of strategies to escape immune surveillance including an altered expression of various immune checkpoints, such as the programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2. The interaction between PD-1 and PD-L1 results in an activation of self-tolerance pathways in both immune cells as well as tumor cells. Thus, these molecules represent excellent targets for T cell-based immunotherapies. However, the efficacy of therapies using checkpoint inhibitors is variable and only a limited number of patients receive a long-term response, while others develop resistances. Therefore, a better insight into the constitutive expression levels and their control as well as the predictive and prognostic value of PD-1/PD-L1, which are controversially discussed due to the methodological assessment, the dynamic and time-related variable expression of these molecules, is urgently required. In this review, the current knowledge of the PD-L1 and PD-1 genes, their expression in immune and tumor cells, the underlying molecular mechanisms of their regulation and their association with clinical parameters and therapy responses are summarized. Full article
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