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J. Clin. Med., Volume 8, Issue 2 (February 2019)

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Cover Story (view full-size image) Chemoresistance is among the most formidable clinical challenges in oncology. One key mediator of [...] Read more.
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Open AccessReview Thromboembolic and Bleeding Complications in Transcatheter Aortic Valve Implantation: Insights on Mechanisms, Prophylaxis and Therapy
J. Clin. Med. 2019, 8(2), 280; https://doi.org/10.3390/jcm8020280
Received: 13 January 2019 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
Transcatheter aortic valve implantation (TAVI) has emerged as an important alternative to surgical aortic valve repair (SAVR) for patients with severe aortic stenosis. This rapidly advancing field has produced new-generation devices being delivered with small delivery sheaths, embolic protection devices and improved retrieval [...] Read more.
Transcatheter aortic valve implantation (TAVI) has emerged as an important alternative to surgical aortic valve repair (SAVR) for patients with severe aortic stenosis. This rapidly advancing field has produced new-generation devices being delivered with small delivery sheaths, embolic protection devices and improved retrieval features. Despite efforts to reduce the rate of thrombotic complications associated with TAVI, valve thrombosis and cerebral ischaemic events post-TAVI continue to be a significant issue. However, the antithrombotic treatments utilised to prevent these dreaded complications are based on weak evidence and are associated with high rates of bleeding, which in itself is associated with adverse clinical outcomes. Recently, experimental data has shed light on the unique mechanisms, particularly the complex haemodynamic changes at sites of TAVI, that underpin the development of post-TAVI thrombosis. These new insights regarding the drivers of TAVI-associated thrombosis, coupled with the ongoing development of novel antithrombotics which do not cause bleeding, hold the potential to deliver newer, safer therapeutic paradigms to prevent post-TAVI thrombotic and bleeding complications. This review highlights the major challenge of post-TAVI thrombosis and bleeding, and the significant issues surrounding current antithrombotic approaches. Moreover, a detailed discussion regarding the mechanisms of post-TAVI thrombosis is provided, in addition to an appraisal of current antithrombotic guidelines, past and ongoing clinical trials, and how novel therapeutics offer the hope of optimizing antithrombotic strategies and ultimately improving patient outcomes. Full article
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Open AccessFeature PaperReview Understanding Peri-Implantitis as a Plaque-Associated and Site-Specific Entity: On the Local Predisposing Factors
J. Clin. Med. 2019, 8(2), 279; https://doi.org/10.3390/jcm8020279
Received: 31 January 2019 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
The prevalence of implant biological complications has grown enormously over the last decade, in concordance with the impact of biofilm and its byproducts upon disease development. Deleterious habits and systemic conditions have been regarded as risk factors for peri-implantitis. However, little is known [...] Read more.
The prevalence of implant biological complications has grown enormously over the last decade, in concordance with the impact of biofilm and its byproducts upon disease development. Deleterious habits and systemic conditions have been regarded as risk factors for peri-implantitis. However, little is known about the influence of local confounders upon the onset and progression of the disease. The present narrative review therefore describes the emerging local predisposing factors that place dental implants/patients at risk of developing peri-implantitis. A review is also made of the triggering factors capable of inducing peri-implantitis and of the accelerating factors capable of interfering with the progression of the disease. Full article
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Open AccessReview Medication in AN: A Multidisciplinary Overview of Meta-Analyses and Systematic Reviews
J. Clin. Med. 2019, 8(2), 278; https://doi.org/10.3390/jcm8020278
Received: 15 January 2019 / Revised: 19 February 2019 / Accepted: 20 February 2019 / Published: 25 February 2019
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Abstract
Drugs are widely prescribed for anorexia nervosa in the nutritional, somatic, and psychiatric fields. There is no systematic overview in the literature, which simultaneously covers all these types of medication. The main aims of this paper are (1) to offer clinicians an overview [...] Read more.
Drugs are widely prescribed for anorexia nervosa in the nutritional, somatic, and psychiatric fields. There is no systematic overview in the literature, which simultaneously covers all these types of medication. The main aims of this paper are (1) to offer clinicians an overview of the evidence-based data in the literature concerning the medication (psychotropic drugs and medication for somatic and nutritional complications) in the field of anorexia nervosa since the 1960s, (2) to draw practical conclusions for everyday practise and future research. Searches were performed on three online databases, namely MEDLINE, Epistemonikos and Web of Science. Papers published between September 2011 and January 2019 were considered. Evidence-based data were identified from meta-analyses, if there were none, from systematic reviews, and otherwise from trials (randomized or if not open-label studies). Evidence-based results are scarce. No psychotropic medication has proved efficacious in terms of weight gain, and there is only weak data suggesting it can alleviate certain psychiatric symptoms. Concerning nutritional and somatic conditions, while there is no specific, approved medication, it seems essential not to neglect the interest of innovative therapeutic strategies to treat multi-organic comorbidities. In the final section we discuss how to use these medications in the overall approach to the treatment of anorexia nervosa. Full article
(This article belongs to the Special Issue Anorexia Nervosa)
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Open AccessArticle Differences in Sexually Transmitted Infections between the Precrisis Period (2000–2007) and the Crisis Period (2008–2014) in Granada, Spain
J. Clin. Med. 2019, 8(2), 277; https://doi.org/10.3390/jcm8020277
Received: 24 January 2019 / Revised: 9 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
Objective: To analyze the difference in the prevalence of sexually transmitted infections (STIs) between two time periods (2000–2007 and 2008–2014, with the latter period characterized by the economic crisis), as well as determine differences in sociodemographic factors, clinical care, and risk indicators. Methods: [...] Read more.
Objective: To analyze the difference in the prevalence of sexually transmitted infections (STIs) between two time periods (2000–2007 and 2008–2014, with the latter period characterized by the economic crisis), as well as determine differences in sociodemographic factors, clinical care, and risk indicators. Methods: This was a retrospective, observational, and analytical study, reviewing 1437 medical records of subjects attending a specialized center in the province of Granada (Spain) for consultation associated with the presence or suspicion of an STI between 2000–2014. Data were collected on variables relating to the research objective. A descriptive and bivariate statistical analysis was performed by multiple logistic regression. Results: In the analysis comparing the presence of STIs between the crisis and non-crisis periods, the percentage of positive diagnoses reached 56.6% compared to 43.4% negative diagnoses during the non-crisis period, while the percentages were 75.2% and 24.8%, respectively, during the crisis period. This difference was statistically significant (p < 0.001) with an odds ratio (OR) of 2.21 after adjusting for age, sex, days since last unprotected sexual intercourse, and partners in the last year. Conclusions: There are significant differences in the prevalence of STIs between the study periods, which is consistent with the reports of some authors regarding the effect of the financial crisis on these conditions; however, it is worth considering other aspects that might explain the differences. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessConcept Paper Dialysis Reimbursement: What Impact Do Different Models Have on Clinical Choices?
J. Clin. Med. 2019, 8(2), 276; https://doi.org/10.3390/jcm8020276
Received: 12 January 2019 / Revised: 14 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
Allowing patients to live for decades without the function of a vital organ is a medical miracle, but one that is not without cost both in terms of morbidity and quality of life and in economic terms. Renal replacement therapy (RRT) consumes between [...] Read more.
Allowing patients to live for decades without the function of a vital organ is a medical miracle, but one that is not without cost both in terms of morbidity and quality of life and in economic terms. Renal replacement therapy (RRT) consumes between 2% and 5% of the overall health care expenditure in countries where dialysis is available without restrictions. While transplantation is the preferred treatment in patients without contraindications, old age and comorbidity limit its indications, and low organ availability may result in long waiting times. As a consequence, 30–70% of the patients depend on dialysis, which remains the main determinant of the cost of RRT. Costs of dialysis are differently defined, and its reimbursement follows different rules. There are three main ways of establishing dialysis reimbursement. The first involves dividing dialysis into a series of elements and reimbursing each one separately (dialysis itself, medications, drugs, transportation, hospitalisation, etc.). The second, known as the capitation system, consists of merging these elements in a per capita reimbursement, while the third, usually called the bundle system, entails identifying a core of procedures intrinsically linked to treatment (e.g., dialysis sessions, tests, intradialyitc drugs). Each one has advantages and drawbacks, and impacts differently on the organization and delivery of care: payment per session may favour fragmentation and make a global appraisal difficult; a correct capitation system needs a careful correction for comorbidity, and may exacerbate competition between public and private settings, the latter aiming at selecting the least complex cases; a bundle system, in which the main elements linked to the dialysis sessions are considered together, may be a good compromise but risks penalising complex patients, and requires a rapid adaptation to treatment changes. Retarding dialysis is a clinical and economical goal, but the incentives for predialysis care are not established and its development may be unfavourable for the provider. A closer cooperation between policymakers, economists and nephrologists is needed to ensure a high quality of dialysis care. Full article
(This article belongs to the Section Nephrology & Urology)
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Open AccessArticle Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population
J. Clin. Med. 2019, 8(2), 275; https://doi.org/10.3390/jcm8020275
Received: 18 January 2019 / Revised: 16 February 2019 / Accepted: 21 February 2019 / Published: 25 February 2019
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Abstract
Genome-wide association studies found genetic variations with modulatory effects for intracranial aneurysm (IA) formations in European and Japanese populations. We aimed to identify the susceptibility of single nucleotide polymorphisms (SNPs) to IA in a Korean population consisting of 250 patients, and 294 controls [...] Read more.
Genome-wide association studies found genetic variations with modulatory effects for intracranial aneurysm (IA) formations in European and Japanese populations. We aimed to identify the susceptibility of single nucleotide polymorphisms (SNPs) to IA in a Korean population consisting of 250 patients, and 294 controls using the Asian-specific Axiom Precision Medicine Research Array. Twenty-nine SNPs reached a genome-wide significance threshold (5 × 10−8). The rs371331393 SNP, with a stop-gain function of ARHGAP32 (11q24.3), showed the most significant association with the risk of IA (OR = 43.57, 95% CI: 21.84–86.95; p = 9.3 × 10−27). Eight out of 29 SNPs—GBA (rs75822236), TCF24 (rs112859779), OLFML2A (rs79134766), ARHGAP32 (rs371331393), CD163L1 (rs138525217), CUL4A (rs74115822), LOC102724084 (rs75861150), and LRRC3 (rs116969723)—demonstrated sufficient statistical power greater than or equal to 0.8. Two previously reported SNPs, rs700651 (BOLL, 2q33.1) and rs6841581 (EDNRA, 4q31.22), were validated in our GWAS (Genome-wide association study). In a subsequent analysis, three SNPs showed a significant difference in expressions: the rs6741819 (RNF144A, 2p25.1) was down-regulated in the adrenal gland tissue (p = 1.5 × 10−6), the rs1052270 (TMOD1. 9q22.33) was up-regulated in the testis tissue (p = 8.6 × 10−10), and rs6841581 (EDNRA, 4q31.22) was up-regulated in both the esophagus (p = 5.2 × 10−12) and skin tissues (1.2 × 10−6). Our GWAS showed novel candidate genes with Korean-specific variations in IA formations. Large population based studies are thus warranted. Full article
(This article belongs to the Section Neuroscience)
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Open AccessReview A Systematic Review of the Short-Term Health Effects of Air Pollution in Persons Living with Coronary Heart Disease
J. Clin. Med. 2019, 8(2), 274; https://doi.org/10.3390/jcm8020274
Received: 30 January 2019 / Revised: 13 February 2019 / Accepted: 21 February 2019 / Published: 24 February 2019
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Abstract
Persons living with chronic medical conditions (such as coronary artery disease (CAD)) are thought to be at increased risk when exposed to air pollution. This systematic review critically evaluated the short-term health effects of air pollution in persons living with CAD. Original research [...] Read more.
Persons living with chronic medical conditions (such as coronary artery disease (CAD)) are thought to be at increased risk when exposed to air pollution. This systematic review critically evaluated the short-term health effects of air pollution in persons living with CAD. Original research articles were retrieved systematically through searching electronic databases (e.g., Medical Literature Analysis and Retrieval System Online (MEDLINE)), cross-referencing, and the authors’ knowledge. From 2884 individual citations, 26 eligible articles were identified. The majority of the investigations (18 of 22 (82%)) revealed a negative relationship between air pollutants and cardiac function or overall health. Heart rate variability (HRV) was the primary cardiovascular outcome measure, with 10 out of 13 studies reporting at least one index of HRV being significantly affected by air pollutants. However, there was some inconsistency in the relationship between HRV and air pollutants, mediated (at least in part) by the confounding effects of beta-blocker medications. In conclusion, there is strong evidence that air pollution can have adverse effects on cardiovascular function in persons living with CAD. All persons living with CAD should be educated on how to monitor air quality, should recognize the potential risks of excessive exposure to air pollution, and be aware of strategies to mitigate these risks. Persons living with CAD should minimize their exposure to air pollution by limiting outdoor physical activity participation when the forecast air quality health index indicates increased air pollution (i.e., an increased risk). Full article
(This article belongs to the Special Issue Cardiac Rehabilitation)
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Open AccessArticle The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma
J. Clin. Med. 2019, 8(2), 273; https://doi.org/10.3390/jcm8020273
Received: 28 January 2019 / Revised: 19 February 2019 / Accepted: 21 February 2019 / Published: 24 February 2019
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Abstract
Background: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. Methods: We investigated the expression of [...] Read more.
Background: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. Methods: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. Results: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. Conclusions: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessArticle The Morphology, Structure, Mechanical Properties and Biocompatibility of Nanotubular Titania Coatings before and after Autoclaving Process
J. Clin. Med. 2019, 8(2), 272; https://doi.org/10.3390/jcm8020272
Received: 29 January 2019 / Revised: 20 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
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Abstract
The autoclaving process is one of the sterilization procedures of implantable devices. Therefore, it is important to assess the impact of hot steam at high pressure on the morphology, structure, and properties of implants modified by nanocomposite coatings. In our works, we focused [...] Read more.
The autoclaving process is one of the sterilization procedures of implantable devices. Therefore, it is important to assess the impact of hot steam at high pressure on the morphology, structure, and properties of implants modified by nanocomposite coatings. In our works, we focused on studies on amorphous titania nanotubes produced by titanium alloy (Ti6Al4V) electrochemical oxidation in the potential range 5–60 V. Half of the samples were drying in argon stream at room temperature, and the second ones were drying additionally with the use of immersion in acetone and drying at 396 K. Samples were subjected to autoclaving and after sterilization they were structurally and morphologically characterized using Raman spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) and scanning electron microscopy (SEM). They were characterized in terms of wettability, mechanical properties, and biocompatibility. Obtained results proved that the autoclaving of amorphous titania nanotube coatings produced at lower potentials (5–15 V) does not affect their morphology and structure regardless of the drying method before autoclaving. Nanotubular coatings produced using higher potentials (20–60 V) require removal of adsorbed water particles from their surface. Otherwise, autoclaving leads to the destruction of the architecture of nanotubular coatings, which is associated with the changing of their mechanical and biointegration properties. Full article
(This article belongs to the Special Issue Biomaterial-Related Infections)
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Open AccessArticle Nicotinamide Improves Functional Recovery via Regulation of the RAGE/JNK/NF-κB Signaling Pathway after Brain Injury
J. Clin. Med. 2019, 8(2), 271; https://doi.org/10.3390/jcm8020271
Received: 31 December 2018 / Revised: 20 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
Brain injuries are a serious global health issue and are the leading cause of neurodegeneration. To date, there is no proper cure and treatment for brain-injury-induced neuropathological conditions because of a lack of sufficient knowledge and the failure to develop a drug due [...] Read more.
Brain injuries are a serious global health issue and are the leading cause of neurodegeneration. To date, there is no proper cure and treatment for brain-injury-induced neuropathological conditions because of a lack of sufficient knowledge and the failure to develop a drug due to the multi-pathological conditions in the brain. Herein, we explored the neurotherapeutic effects of Nicotinamide (NAM), against brain injury-induced neurodegeneration and behavioral problems. Treating injured mouse brains with NAM, for 7 days, significantly ameliorated several pathological events. Interestingly, NAM treatment significantly inhibited the injury-induced activation of receptor for advanced glycation end-products (RAGE), c-Jun N-terminal kinases (JNK), and neuroinflammatory mediators, such as NF-κB, TNF-α, IL-1β, and NOS2 in the brain, and it also regulated the levels of apoptotic markers, including Bax, caspase-3, and Bcl-2. Furthermore, treatment using NAM in TBI mice, significantly reversed synaptic protein loss and improved memory impairments and behavioral outcomes. Our findings suggested that NAM treatment reduced injury-induced secondary neurodegenerative pathology by modulating RAGE/JNK/NF-κB signaling in mice. Therefore, we recommend that NAM would be a safe and efficient therapeutic agent against brain-injury-induced neurodegeneration. Full article
(This article belongs to the Section Neuroscience)
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Open AccessReview Cardiac Biomarkers in the Emergency Department: The Role of Soluble ST2 (sST2) in Acute Heart Failure and Acute Coronary Syndrome—There is Meat on the Bone
J. Clin. Med. 2019, 8(2), 270; https://doi.org/10.3390/jcm8020270
Received: 30 January 2019 / Revised: 18 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
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Abstract
Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated [...] Read more.
Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated with an increased risk of adverse left ventricular remodeling. Therefore, sST2 could represent a useful tool that could help the risk stratification and diagnostic and therapeutic work-up of patients admitted to an emergency department. With this review, based on recent literature, we have built sST2-assisted flowcharts applicable to three very common clinical scenarios of the emergency department: Acute heart failure, type 1, and type 2 acute myocardial infarction. In particular, we combined sST2 levels together with clinical and instrumental evaluation in order to offer a practical tool for emergency medicine physicians. Full article
(This article belongs to the Special Issue Cardiovascular and Neurological Emergency)
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Open AccessArticle Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants
J. Clin. Med. 2019, 8(2), 269; https://doi.org/10.3390/jcm8020269
Received: 23 January 2019 / Revised: 14 February 2019 / Accepted: 18 February 2019 / Published: 22 February 2019
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Abstract
Background: African-Americans (AAs) have a 3.5% carrier prevalence of Transthyretin (TTR) Val122Ile mutation (rs76992529), which is the genetic cause of a hereditary form of amyloidosis. Methods: We investigated the medical history of Val122Ile carriers and assessed the role of a [...] Read more.
Background: African-Americans (AAs) have a 3.5% carrier prevalence of Transthyretin (TTR) Val122Ile mutation (rs76992529), which is the genetic cause of a hereditary form of amyloidosis. Methods: We investigated the medical history of Val122Ile carriers and assessed the role of a non-coding variation in 4361 unrelated AAs. Results: We observed that the Ile122 allele was associated with a 6.8-fold increase in the odds of having 10 or more outpatient surgeries (p = 7.81 × 10−5). Stratifying the analysis by sex, the Ile122 allele was associated with a 15.2-fold increase in the odds of having 10 or more outpatient surgeries in men (p = 6.49 × 10−7). A similar sex difference was observed with respect to the association of Val122Ile with musculoskeletal and connective-tissue disorders in an independent cohort of British subjects (n = 361,194, p = 2.47 × 10−13; nmale = 167,020, pmale = 4.02 × 10−24). In Val122Ile African-American carriers, we observed that haplotypes in the upstream region regulating TTR hepatic expression are associated with having 10 or more outpatient surgeries (p = 2.56 × 10−9). Conclusions: TTR Val122Ile showed a large effect with respect to an extreme phenotype identified in medical history that may be related to osteoarthritis, an early sign of the disease. Additionally, the non-coding variation appears to accelerate the negative consequences associated with Val122Ile mutation via TTR expression regulation. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessReview Central Nervous System Effects of Oral Propranolol for Infantile Hemangioma: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(2), 268; https://doi.org/10.3390/jcm8020268
Received: 5 February 2019 / Revised: 16 February 2019 / Accepted: 20 February 2019 / Published: 22 February 2019
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Abstract
Concerns about the effects of propranolol on the central nervous system (CNS) in the infantile hemangioma (IH) population have been raised. We conducted a meta-analysis of the CNS and sleep-related effects of oral propranolol in IH patients. PubMed, Embase, Cochrance, Web of Science, [...] Read more.
Concerns about the effects of propranolol on the central nervous system (CNS) in the infantile hemangioma (IH) population have been raised. We conducted a meta-analysis of the CNS and sleep-related effects of oral propranolol in IH patients. PubMed, Embase, Cochrance, Web of Science, and Clinicaltrials.gov were searched for relevant studies. We included clinical trials that compared oral propranolol with other treatments among IH patients under 6 years old and monitored and reported any adverse events. Study characteristics, types and number of adverse events were abstracted. Cochrane Collaboration Risk of Bias Tool was used to assess risk of bias. Our main outcomes were CNS and sleep-related effects. Random-effects models were used to estimate the pooled risk ratio. We did not observe statistically significant associations between oral propranolol and CNS or sleep-related effects. Oral propranolol appeared to have a safer profile of CNS effects than corticosteroids (RR = 0.27, 95% CI 0.02–3.00), but had an increased risk versus non-corticosteroids (for CNS effect, RR = 1.40, 95% CI 0.86–2.27; for sleep-related effects, RR = 1.63, 95% CI 0.88–3.03). Despite no statistically significant associations, there were suggestive findings of increased CNS effects and sleep-related risk of propranolol versus non-corticosteroids. In practice, CNS and sleep-related events should be monitored more closely among IH patients treated with oral propranolol. Full article
(This article belongs to the Section Dermatology)
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Open AccessPerspective Why Have Detection, Understanding and Management of Kidney Hypoxic Injury Lagged behind Those for the Heart?
J. Clin. Med. 2019, 8(2), 267; https://doi.org/10.3390/jcm8020267
Received: 6 February 2019 / Revised: 17 February 2019 / Accepted: 19 February 2019 / Published: 21 February 2019
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Abstract
The outcome of patients with acute myocardial infarction (AMI) has dramatically improved over recent decades, thanks to early detection and prompt interventions to restore coronary blood flow. In contrast, the prognosis of patients with hypoxic acute kidney injury (AKI) remained unchanged over the [...] Read more.
The outcome of patients with acute myocardial infarction (AMI) has dramatically improved over recent decades, thanks to early detection and prompt interventions to restore coronary blood flow. In contrast, the prognosis of patients with hypoxic acute kidney injury (AKI) remained unchanged over the years. Delayed diagnosis of AKI is a major reason for this discrepancy, reflecting the lack of symptoms and diagnostic tools indicating at real time altered renal microcirculation, oxygenation, functional derangement and tissue injury. New tools addressing these deficiencies, such as biomarkers of tissue damage are yet far less distinctive than myocardial biomarkers and advanced functional renal imaging technologies are non-available in the clinical practice. Moreover, our understanding of pathogenic mechanisms likely suffers from conceptual errors, generated by the extensive use of the wrong animal model, namely warm ischemia and reperfusion. This model parallels mechanistically type I AMI, which properly represents the rare conditions leading to renal infarcts, whereas common scenarios leading to hypoxic AKI parallel physiologically type II AMI, with tissue hypoxic damage generated by altered oxygen supply/demand equilibrium. Better understanding the pathogenesis of hypoxic AKI and its management requires a more extensive use of models of type II-rather than type I hypoxic AKI. Full article
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Open AccessArticle Genetic Variants in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Bayesian Approach and Systematic Review
J. Clin. Med. 2019, 8(2), 266; https://doi.org/10.3390/jcm8020266
Received: 31 January 2019 / Revised: 13 February 2019 / Accepted: 19 February 2019 / Published: 21 February 2019
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Abstract
A number of genome-wide association studies (GWASs) and meta-analyses of genetic variants have been performed in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We reinterpreted previous studies using false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP). This study searched publications in PubMed and [...] Read more.
A number of genome-wide association studies (GWASs) and meta-analyses of genetic variants have been performed in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We reinterpreted previous studies using false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP). This study searched publications in PubMed and Excerpta Medica Database (EMBASE) up to February 2018. Identification of noteworthy associations were analyzed using FPRP and BFDP, and data (i.e., odds ratio (OR), 95% confidence interval (CI), p-value) related to significant associations were separately extracted. Using filtered gene variants, gene ontology (GO) enrichment analysis and protein–protein interaction (PPI) networks were performed. Overall, 241 articles were identified, and 7 were selected for analysis. Single nucleotide polymorphisms (SNPs) discovered by GWASs were shown to be noteworthy, whereas only 27% of significant results from meta-analyses of observational studies were noteworthy. Eighty-five percent of SNPs with borderline p-values (5.0 × 10−8 < p < 0.05) in GWASs were found to be noteworthy. No overlapping SNPs were found between PR3-ANCA and MPO-ANCA vasculitis. GO analysis revealed immune-related GO terms, including “antigen processing and presentation of peptide or polysaccharide antigen via major histocompatibility complex (MHC) class II”, “interferon-gamma-mediated (IFN-γ) signaling pathway”. By using FPRP and BFDP, network analysis of noteworthy genetic variants discovered genetic risk factors associated with the IFN-γ pathway as novel mechanisms potentially implicated in the complex pathogenesis of ANCA-associated vasculitis. Full article
(This article belongs to the Section Immunology)
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Open AccessArticle Blood-Flow Restriction Resistance Exercise for Older Adults with Knee Osteoarthritis: A Pilot Randomized Clinical Trial
J. Clin. Med. 2019, 8(2), 265; https://doi.org/10.3390/jcm8020265
Received: 31 January 2019 / Revised: 15 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
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Abstract
In a pilot randomized clinical trial, participants aged ≥60 years (n = 35) with physical limitations and symptomatic knee osteoarthritis (OA) were randomized to 12 weeks of lower-body low-load resistance training with blood-flow restriction (BFR) or moderate-intensity resistance training (MIRT) to evaluate [...] Read more.
In a pilot randomized clinical trial, participants aged ≥60 years (n = 35) with physical limitations and symptomatic knee osteoarthritis (OA) were randomized to 12 weeks of lower-body low-load resistance training with blood-flow restriction (BFR) or moderate-intensity resistance training (MIRT) to evaluate changes in muscle strength, pain, and physical function. Four exercises were performed three times per week to volitional fatigue using 20% and 60% of one repetition maximum (1RM). Study outcomes included knee extensor strength, gait speed, Short Physical Performance Battery (SPPB) performance, and pain via the Western Ontario and McMaster Universities OA Index (WOMAC). Per established guidance for pilot studies, primary analyses for the trial focused on safety, feasibility, and effect sizes/95% confidence intervals of dependent outcomes to inform a fully-powered trial. Across three speeds of movement, the pre- to post-training change in maximal isokinetic peak torque was 9.96 (5.76, 14.16) Nm while the mean difference between groups (BFR relative to MIRT) was −1.87 (−10.96, 7.23) Nm. Most other directionally favored MIRT, though more spontaneous reports of knee pain were observed (n = 14) compared to BFR (n = 3). BFR may have lower efficacy than MIRT in this context—though a fully-powered trial is needed to definitively address this hypothesis. Full article
(This article belongs to the Special Issue Sarcopenia in Older Adults)
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Open AccessArticle Aspirin Use among Adults with Cardiovascular Disease in the United States: Implications for an Intervention Approach
J. Clin. Med. 2019, 8(2), 264; https://doi.org/10.3390/jcm8020264
Received: 30 January 2019 / Revised: 13 February 2019 / Accepted: 18 February 2019 / Published: 20 February 2019
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Abstract
Cardiovascular disease (CVD) is a major underlying cause of death, with high economic burden in most countries, including the United States. Lifestyle modifications and the use of antiplatelet therapy, such as aspirin, can contribute significantly to secondary prevention of CVD in adults. This [...] Read more.
Cardiovascular disease (CVD) is a major underlying cause of death, with high economic burden in most countries, including the United States. Lifestyle modifications and the use of antiplatelet therapy, such as aspirin, can contribute significantly to secondary prevention of CVD in adults. This study examined the prevalence and associated factors of aspirin use for the secondary prevention of angina pectoris, myocardial infarction (MI), and cerebrovascular disease (stroke) in a sample of American adults. The 2015 Behavioral Risk Factor Surveillance System (BRFSS) dataset was analyzed for this cross-sectional study. Almost 16% of the study population (N = 441,456) had angina, MI, or stroke. Weighted percentages of respondents with angina, MI, and stroke were 4%, 4.3%, and 3%, respectively. Overall, weighted prevalence of daily (or every other day) aspirin use was about 65%, 71%, and 57% among respondents with angina, MI, and stroke, respectively. Factors that were significantly associated with aspirin use included male sex, more than high school education, high blood pressure, diabetes, and less than excellent general health. There were existing differences among individuals with CVD based on diagnosis, demographic and socioeconomic status in the use of aspirin for secondary prevention. Resources for promoting aspirin use should be directed toward groups with lower utilization. Full article
(This article belongs to the Section Cardiology)
Open AccessArticle A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
J. Clin. Med. 2019, 8(2), 263; https://doi.org/10.3390/jcm8020263
Received: 11 January 2019 / Revised: 13 February 2019 / Accepted: 14 February 2019 / Published: 20 February 2019
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Abstract
High-grade gliomas (HGGs) carry a dismal prognosis despite current treatments. We previously confirmed the safety and immunogenicity of a vaccine treatment targeting tumor angiogenesis with synthetic peptides, for vascular endothelial growth factor receptor (VEGFR) epitopes in recurrent HGG patients. In this study, we [...] Read more.
High-grade gliomas (HGGs) carry a dismal prognosis despite current treatments. We previously confirmed the safety and immunogenicity of a vaccine treatment targeting tumor angiogenesis with synthetic peptides, for vascular endothelial growth factor receptor (VEGFR) epitopes in recurrent HGG patients. In this study, we evaluated a novel vaccine therapy targeting not only tumor vasculature but also tumor cells, using multiple glioma oncoantigen (GOA)/glioma angiogenesis-associated antigen (GAAA) peptides in HLA-A2402+ recurrent/progressive HGG patients. The vaccine included peptide epitopes from four GOAs (LY6K, DEPDC1, KIF20A, and FOXM1) and two GAAAs (VEGFR1 and VEGFR2). Ten patients received subcutaneous vaccinations. The primary endpoint was the safety of the treatment. T-lymphocyte responses against GOA/GAAA epitopes and treatment response were evaluated secondarily. The treatment was well tolerated without any severe systemic adverse events. The vaccinations induced immunoreactivity to at least three vaccine-targeted GOA/GAAA in all six evaluable patients. The median overall survival time in all patients was 9.2 months. Five achieved progression-free status lasting at least six months. Two recurrent glioblastoma patients demonstrated stable disease. One patient with anaplastic oligoastrocytoma achieved complete response nine months after the vaccination. Taken together, this regimen was well tolerated and induced robust GOA/GAAA-specific T-lymphocyte responses in recurrent/progressive HGG patients. Full article
(This article belongs to the Special Issue The Immunology and Biology of Brain Tumors)
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Open AccessArticle Early Effects of Sacubitril/Valsartan on Exercise Tolerance in Patients with Heart Failure with Reduced Ejection Fraction
J. Clin. Med. 2019, 8(2), 262; https://doi.org/10.3390/jcm8020262
Received: 22 January 2019 / Revised: 17 February 2019 / Accepted: 18 February 2019 / Published: 20 February 2019
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Abstract
Background. Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF. Methods. [...] Read more.
Background. Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF. Methods. We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy. Results. At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3–14.9 months) systolic blood pressure decreased from 117 ± 14 to 101 ± 12 mmHg (p < 0.0001), left ventricular ejection fraction (LVEF) increased from 27 ± 6 to 29.7 ± 7% (p < 0.0001), peak oxygen consumption (VO2) improved from 14.6 ± 3.3 (% of predicted = 53.8 ± 14.1) to 17.2 ± 4.7 mL/kg/min (% of predicted = 64.7 ± 17.8) (p < 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO2 Slope) decreased from 34.1 ± 6.3 to 31.7 ± 6.1 (p = 0.006), VO2 at anaerobic threshold increased from 11.3 ± 2.6 to 12.6 ± 3.5 mL/kg/min (p = 0.007), oxygen pulse increased from 11.5 ± 3.0 to 13.4 ± 4.3 mL/kg/min (p < 0.0001), and ∆VO2/∆Work increased from 9.2 ± 1.5 to 10.1 ± 1.8 mL/min/watt (p = 0.0002). Conclusion. Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO2, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement. Full article
(This article belongs to the Special Issue Cardiac Rehabilitation)
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Open AccessArticle The Microbiological Characteristics of Carbapenem-Resistant Enterobacteriaceae Carrying the mcr-1 Gene
J. Clin. Med. 2019, 8(2), 261; https://doi.org/10.3390/jcm8020261
Received: 6 January 2019 / Revised: 15 February 2019 / Accepted: 18 February 2019 / Published: 19 February 2019
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Abstract
Objectives: This study aims to assess the prevalence of the mcr-1 gene among carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical specimens and to further investigate the clinical significance and microbiological characteristics of CRE carrying the mcr-1 gene. Methods: Four hundred and twenty-three CRE isolates [...] Read more.
Objectives: This study aims to assess the prevalence of the mcr-1 gene among carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical specimens and to further investigate the clinical significance and microbiological characteristics of CRE carrying the mcr-1 gene. Methods: Four hundred and twenty-three CRE isolates were screened for the presence of the mcr-1 gene. After identification, their clinical significance, antibiotic susceptibility, and antibiotic resistance mechanisms including the ESBL gene, carbapenemase gene, outer membrane protein (OMP), and plasmid sequencing were assessed. Results: Only four (0.9%) isolates of carbapenem-resistant Escherichia coli (E. coli) were found to carry the mcr-1 gene and demonstrated different pulsed-field gel electrophoresis (PFGE) patterns and sequence types (ST). While one patient was considered as having mcr-1-positive carbapenem-resistant E. coli (CREC) colonization, the other three mcr-1-positive CREC-related infections were classified as nosocomial infections. Only amikacin and tigecycline showed good in vitro activity against these four isolates, and three of them had a minimum inhibitory concentration with colistin of ≥4 mg/L. In the colistin-susceptible isolate, mcr-1 was nonfunctional due to the insertion of another gene. In addition, all of the mcr-1-positive CREC contained various resistant genes, such as AmpCCMY, blaNDM, blaTEM, blaSHV, and blaCTX. In addition, one strain (EC1037) had loss of the OMP. Conclusions: The emergence of the mcr-1 gene among CRE, especially E. coli, remains worth our attention due to its resistance to most antibiotics, and a further national survey is warranted. Full article
(This article belongs to the Section Microbiology & Parasitology)
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Open AccessArticle A Pilot Study of Infrared Thermography Based Assessment of Local Skin Temperature Response in Overweight and Lean Women during Oral Glucose Tolerance Test
J. Clin. Med. 2019, 8(2), 260; https://doi.org/10.3390/jcm8020260
Received: 9 January 2019 / Revised: 6 February 2019 / Accepted: 14 February 2019 / Published: 19 February 2019
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Abstract
Obesity is recognized as a major public health issue, as it is linked to the increased risk of severe pathological conditions. The aim of this pilot study is to evaluate the relations between adiposity (and biophysical characteristics) and temperature profiles under thermoneutral conditions [...] Read more.
Obesity is recognized as a major public health issue, as it is linked to the increased risk of severe pathological conditions. The aim of this pilot study is to evaluate the relations between adiposity (and biophysical characteristics) and temperature profiles under thermoneutral conditions in normal and overweight females, investigating the potential role of heat production/dissipation alteration in obesity. We used Infrared Thermography (IRT) to evaluate the thermogenic response to a metabolic stimulus performed with an oral glucose tolerance test (OGTT). Thermographic images of the right hand and of the central abdomen (regions of interests) were obtained basally and during the oral glucose tolerance test (3 h OGTT with the ingestion of 75 g of oral glucose) in normal and overweight females. Regional temperature vs BMI, % of body fat and abdominal skinfold were statistically compared between two groups. The study showed that mean abdominal temperature was significantly greater in lean than overweight participants (34.11 ± 0.70 °C compared with 32.92 ± 1.24 °C, p < 0.05). Mean hand temperature was significantly greater in overweight than lean subjects (31.87 ± 3.06 °C compared with 28.22 ± 3.11 °C, p < 0.05). We observed differences in temperature profiles during OGTT between lean and overweight subjects: The overweight individuals depict a flat response as compared to the physiological rise observed in lean individuals. This observed difference in thermal pattern suggests an energy rate imbalance towards nutrients storage of the overweight subjects. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessBrief Report Somatosensory Electrical Stimulation Does Not Improve Motor Coordination in Patients with Unilateral Knee Osteoarthritis
J. Clin. Med. 2019, 8(2), 259; https://doi.org/10.3390/jcm8020259
Received: 25 January 2019 / Revised: 12 February 2019 / Accepted: 18 February 2019 / Published: 19 February 2019
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Abstract
Non-surgical treatment of knee osteoarthritis (KOA) is often focused on the motor component of KOA even though there is evidence that sensory dysfunctions play an important role in the impaired control of the affected joint. Excitation of sensory afferents can increase motor function [...] Read more.
Non-surgical treatment of knee osteoarthritis (KOA) is often focused on the motor component of KOA even though there is evidence that sensory dysfunctions play an important role in the impaired control of the affected joint. Excitation of sensory afferents can increase motor function by exploiting the nervous system’s ability to adapt to changing environments (i.e., neuronal plasticity). Therefore, the aim of this study was to explore the acute effects of a single session (30 min) of sensory intervention targeting neuronal plasticity using low-frequency (10 Hz) somatosensory electrical stimulation (SES) of the femoral nerve. We evaluated the effects of SES on the position and force control of the affected knee and self-reported pain in KOA patients (n = 14) in a sham-controlled randomized trial. The results showed that SES did not improve measures of lower-limb motor coordination compared to sham stimulation in KOA patients, nor did it improve self-reported knee function and pain (all p > 0.05). In conclusion, despite sensory involvement in KOA, the sensory intervention used in the present explorative study did not relieve self-reported pain, which may underlie the absence of an effect on measures of motor coordination. In sum, the present explorative study showed that SES alone does not improve motor coordination in KOA patients. Full article
(This article belongs to the Section Orthopedics)
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Open AccessArticle Kidney Involvement in Patients with Type 1 Autoimmune Pancreatitis
J. Clin. Med. 2019, 8(2), 258; https://doi.org/10.3390/jcm8020258
Received: 20 January 2019 / Revised: 7 February 2019 / Accepted: 14 February 2019 / Published: 18 February 2019
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Abstract
Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with a strong lymphocytic infiltration as the pathological hallmark and other organ involvement (OOI). IgG4-related kidney disease (IgG4-RKD) was first reported as an extrapancreatic manifestation of AIP in 2004. The [...] Read more.
Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with a strong lymphocytic infiltration as the pathological hallmark and other organ involvement (OOI). IgG4-related kidney disease (IgG4-RKD) was first reported as an extrapancreatic manifestation of AIP in 2004. The aim of the present study was to determine the frequency and clinical impact of kidney lesions observed in patients with AIP type 1. Methods: We performed a single-centre retrospective study on a prospectively collected cohort of patients with a histologically proven or highly probable diagnosis of AIP according to the International Consensus Diagnostic Criteria (ICDC) classification. Results: Seventy-one patients with AIP were evaluated. AIP type 1 was diagnosed in 62 (87%) patients. Kidney involvement was present in 17 (27.4%) patients with AIP type 1: 15 (88.2%) males and 2 (11.8%) females. Laboratory and/or imaging signs of kidney involvement were presented at the time of AIP diagnosis in eight (47.1%) patients. In other patients, the onset of kidney involvement occurred between four months and eight years following diagnosis. At the time of the diagnosis of kidney involvement, eight (47.1%) patients showed elevated creatinine, and nine (52.9%) patients showed normal serum creatinine. None of the patients were treated with dialysis. Conclusions: IgG4-RKD was present in 27.4% of patients with AIP type 1, with male gender predominance. In cases of early diagnosis and cortisone treatment, the clinical course was mild in most cases. Regular laboratory control of renal function should be a part of the follow-up of patients with AIP type 1. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessArticle Expression of SLC5A5 in Circulating Tumor Cells May Distinguish Follicular Thyroid Carcinomas from Adenomas: Implications for Blood-Based Preoperative Diagnosis
J. Clin. Med. 2019, 8(2), 257; https://doi.org/10.3390/jcm8020257
Received: 29 January 2019 / Revised: 13 February 2019 / Accepted: 13 February 2019 / Published: 18 February 2019
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Abstract
Preoperative diagnosis of thyroid nodules reduces unnecessary surgery. Circulating tumor cells (CTCs) may contain information of primary tumor(s). We asked whether the peripheral blood expression of genes specific for circulating tumor cells (CTCs) differentiates benign thyroid nodules from malignant nodules. Peripheral blood mononuclear [...] Read more.
Preoperative diagnosis of thyroid nodules reduces unnecessary surgery. Circulating tumor cells (CTCs) may contain information of primary tumor(s). We asked whether the peripheral blood expression of genes specific for circulating tumor cells (CTCs) differentiates benign thyroid nodules from malignant nodules. Peripheral blood mononuclear cells from thyroid nodule patients (n = 20) were isolated preoperatively and the expression of seven CTC-associated genes was measured in patients with thyroid nodule(s) (n = 20). Among the tested genes, the expression of SLC5A5 and LGALS3 were validated in a larger number of patients (n = 64) and our results show that SLC5A5 expression differentiated follicular adenomas from follicular carcinomas (area under the curve (AUC) = 0.831). The expression of SLC5A5 in CTCs may preoperatively distinguish thyroid follicular adenomas from follicular carcinomas. Full article
(This article belongs to the Section Cell Biology)
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Open AccessReview The Emerging Role of Robotic Surgery among Minimally Invasive Surgical Approaches in the Treatment of Hypopharyngeal Carcinoma: Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(2), 256; https://doi.org/10.3390/jcm8020256
Received: 26 January 2019 / Revised: 11 February 2019 / Accepted: 12 February 2019 / Published: 18 February 2019
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Abstract
The aim of this systematic review with meta-analysis was to investigate the available literature on transoral approaches in the treatment of hypopharyngeal squamous cell carcinoma, with a special focus on transoral robotic surgery (TORS). A systematic review was conducted according to the PRISMA [...] Read more.
The aim of this systematic review with meta-analysis was to investigate the available literature on transoral approaches in the treatment of hypopharyngeal squamous cell carcinoma, with a special focus on transoral robotic surgery (TORS). A systematic review was conducted according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) check-list, and 15 studies were included. Five of the included studies evaluated TORS, while ten studies focused on transoral laser microsurgery (TLM) for the treatment of early or advanced stage hypopharyngeal cancer. Overall, survival rates of TLM and TORS studies, analyzed together in the cumulative meta-analysis, were 66.4% (95% confidence interval (CI) 54.3%–76.7%) at 36+ months of follow up. The TORS subgroup showed a higher cumulative survival rate (85.5%, 95% CI 55.8%–96.5%) compared to TLM (58.5%, 95% CI 46.6%–69.6%). Cumulative data showed that 29.3% (95% CI 24.0%–35.3%) of deaths were attributable to cancer. The results were similar between TLM and TORS studies. The larynx function preservation cumulative rate was 94.3% (95% CI 91.8%–96.1%). The results were similar among the two subgroups. The present review supports the use of transoral approaches in the treatment of hypopharyngeal cancer. TORS is oncologically sound and provides excellent functional results with low complication rates. Full article
(This article belongs to the Special Issue Robotic Surgery)
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Open AccessReview Coronary Physiology in the Cardiac Catheterization Laboratory
J. Clin. Med. 2019, 8(2), 255; https://doi.org/10.3390/jcm8020255
Received: 10 December 2018 / Revised: 9 February 2019 / Accepted: 14 February 2019 / Published: 18 February 2019
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Abstract
Coronary angiography has been the principle modality for assessing the severity of atherosclerotic coronary artery disease for several decades. However, there is a complex relationship between angiographic coronary stenosis and the presence or absence of myocardial ischemia. Recent technological advances now allow for [...] Read more.
Coronary angiography has been the principle modality for assessing the severity of atherosclerotic coronary artery disease for several decades. However, there is a complex relationship between angiographic coronary stenosis and the presence or absence of myocardial ischemia. Recent technological advances now allow for the assessment of coronary physiology in the catheterization laboratory at the time of diagnostic coronary angiography. Early studies focused on coronary flow reserve (CFR) but more recent work has demonstrated the physiologic accuracy and prognostic value of the fractional flow reserve (FFR) and instantaneous wave free ratio (iFR) for the assessment of coronary artery disease. These measurements have been validated in large multi-center clinical trials and have become indispensable tools for guiding revascularization in the cardiac catheterization laboratory. The physiological assessment of chest pain in the absence of epicardial coronary artery disease involves coronary thermodilution to obtain the index of microcirculatory resistance (IMR) or Doppler velocity measurement to determine the coronary flow velocity reserve (CFVR). Physiology-based coronary artery assessment brings “personalized medicine” to the catheterization laboratory and allows cardiologists and referring providers to make decisions based on objective findings and evidence-based treatment algorithms. The purpose of this review is to describe the theory, technical aspects, and relevant clinical trials related to coronary physiology assessment for an intended audience of general medical practitioners. Full article
(This article belongs to the Special Issue Advances in Interventional Cardiology and Vascular Medicine)
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Open AccessReview Long-Term Safety and Real-World Effectiveness of Trastuzumab in Breast Cancer
J. Clin. Med. 2019, 8(2), 254; https://doi.org/10.3390/jcm8020254
Received: 22 January 2019 / Revised: 14 February 2019 / Accepted: 15 February 2019 / Published: 18 February 2019
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Abstract
Trastuzumab is a milestone in the treatment of human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), in both the early and metastatic settings. Over the last two decades, clinical trials have established the good safety profile of trastuzumab. Cardiotoxicity remains [...] Read more.
Trastuzumab is a milestone in the treatment of human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), in both the early and metastatic settings. Over the last two decades, clinical trials have established the good safety profile of trastuzumab. Cardiotoxicity remains the most frequent adverse event, more commonly exemplified by an asymptomatic decline in the left ventricular ejection fraction rather than congestive heart failure. Results from several long-term (>5 years) safety analyses have been recently published, with the inherent evidence substantially confirming the findings from previous trials. The clinical experience gained over the years in the use of trastuzumab has also fueled a number of observational studies focused on the effectiveness of this drug in the real-world settings. We herein reviewed the evidence available from tree major databases, namely, PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), to explore and critically discuss key issues related to the long-term safety and effectiveness of trastuzumab in clinical practice. Full article
(This article belongs to the Section Oncology)
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Open AccessReview Cardiovascular Health Benefits of Exercise Training in Persons Living with Type 1 Diabetes: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(2), 253; https://doi.org/10.3390/jcm8020253
Received: 24 January 2019 / Revised: 7 February 2019 / Accepted: 13 February 2019 / Published: 17 February 2019
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Abstract
Exercise is advocated in the management of type 1 diabetes (T1D), but the effects of different forms of exercise training on cardiovascular risk factors in T1D still remain unclear. The aim of this study was to conduct a systematic review and meta-analysis on [...] Read more.
Exercise is advocated in the management of type 1 diabetes (T1D), but the effects of different forms of exercise training on cardiovascular risk factors in T1D still remain unclear. The aim of this study was to conduct a systematic review and meta-analysis on exercise training for cardiovascular risk factors in T1D. Six electronic databases were systematically searched for randomized or non-randomized controlled studies reporting associations between exercise training and cardiovascular risk factors in T1D. Weighted mean differences (WMD) of each cardiovascular risk factor between exercise groups and control groups were calculated using a random effects model. A total of 24 studies reported the effects of exercise training on cardiovascular risk factors. Exercise training increased maximal aerobic power (3.01 mL·kg−1·min−1, 95% confidence interval, CI, 0.94 to 6.38) and reduced glycated hemoglobin (HbA1c; −0.45%, 95% CI −0.73 to −0.17), daily insulin dosage (−0.88 U·kg−1, 95% CI −1.27 to −0.48), and total cholesterol (−0.38 mmol·L−1, 95% CI −0.71 to −0.04). Exercise training did not lead to consistent changes in body mass index (BMI), blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). In persons living with T1D, exercise training is associated with a beneficial cardiovascular profile, including improvements in lipid profile, glycemic control (decreased daily insulin dosage and HbA1c), and aerobic fitness. Full article
(This article belongs to the Special Issue Cardiac Rehabilitation)
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Open AccessArticle A Peri-Implant Disease Risk Score for Patients with Dental Implants: Validation and the Influence of the Interval between Maintenance Appointments
J. Clin. Med. 2019, 8(2), 252; https://doi.org/10.3390/jcm8020252
Received: 21 January 2019 / Revised: 10 February 2019 / Accepted: 13 February 2019 / Published: 17 February 2019
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Abstract
Background: There is a need for tools that provide prediction of peri-implant disease. The purpose of this study was to validate a risk score for peri-implant disease and to assess the influence of the recall regimen in disease incidence based on a five-year [...] Read more.
Background: There is a need for tools that provide prediction of peri-implant disease. The purpose of this study was to validate a risk score for peri-implant disease and to assess the influence of the recall regimen in disease incidence based on a five-year retrospective cohort. Methods: Three hundred and fifty-three patients with 1238 implants were observed. A risk score was calculated from eight predictors and risk groups were established. Relative risk (RR) was estimated using logistic regression, and the c-statistic was calculated. The effect/impact of the recall regimen (≤ six months; > six months) on the incidence of peri-implant disease was evaluated for a subset of cases and matched controls. The RR and the proportional attributable risk (PAR) were estimated. Results: At baseline, patients fell into the following risk profiles: low-risk (n = 102, 28.9%), moderate-risk (n = 68, 19.3%), high-risk (n = 77, 21.8%), and very high-risk (n = 106, 30%). The incidence of peri-implant disease over five years was 24.1% (n = 85 patients). The RR for the risk groups was 5.52 (c-statistic = 0.858). The RR for a longer recall regimen was 1.06, corresponding to a PAR of 5.87%. Conclusions: The risk score for estimating peri-implant disease was validated and showed very good performance. Maintenance appointments of < six months or > six months did not influence the incidence of peri-implant disease when considering the matching of cases and controls by risk profile. Full article
(This article belongs to the Special Issue Implant Dentistry—Trends, Challenges and Innovations)
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Open AccessArticle Biobanking: Objectives, Requirements, and Future Challenges—Experiences from the Munich Vascular Biobank
J. Clin. Med. 2019, 8(2), 251; https://doi.org/10.3390/jcm8020251
Received: 9 January 2019 / Revised: 1 February 2019 / Accepted: 12 February 2019 / Published: 16 February 2019
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Abstract
Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the [...] Read more.
Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine. Full article
(This article belongs to the Special Issue Biobanking and Regenerative Medicine)
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