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J. Clin. Med., Volume 7, Issue 12 (December 2018)

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Cover Story (view full-size image) Neutrophils are the most abundant immune cell population in the blood, however their role in the [...] Read more.
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Open AccessReview Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer
J. Clin. Med. 2018, 7(12), 567; https://doi.org/10.3390/jcm7120567
Received: 2 November 2018 / Revised: 5 December 2018 / Accepted: 10 December 2018 / Published: 19 December 2018
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Abstract
Background: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data
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Background: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data sources and study eligibility criteria: A systematic literature search was performed in PubMed, with keywords “HIPEC” and “colorectal cancer”, according to established guidelines. Articles were systematically screened, selecting 87 publications complemented by 48 publications identified through extended search for subsequent synthesis and evaluation, extracting inter alia details on used drugs, dosage, temperature, exposure times, and carrier solutions. Results: Compiled publications contained 171 reports on HIPEC conduct foremost with mitomycin C and oxaliplatin, but also other drugs and drug combinations, comprising at least 60 different procedures. We hence provide an overview of interconnections between HIPEC protocols, used drugs and carrier solutions as well as their volumes. In addition, HIPEC temperatures and dosing benchmarks, as well as an estimate of in vivo resulting drug concentrations are demonstrated. Conclusions and implications: Owing to recent developments, HIPEC conduct and practices need to be reassessed. Unfortunately, imprecise and lacking reporting is frequent, which is why minimal information requirements should be established for HIPEC and the introduction of final drug concentrations for comparability reasons seems sensible. Full article
(This article belongs to the Section Pharmacology)
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Open AccessArticle Comparison of Intra-Operative Vital Sign Changes during Total Thyroidectomy in Patients with Controlled and Uncontrolled Graves’ Disease
J. Clin. Med. 2018, 7(12), 566; https://doi.org/10.3390/jcm7120566
Received: 20 November 2018 / Revised: 11 December 2018 / Accepted: 18 December 2018 / Published: 19 December 2018
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Abstract
Thyroid storm (TS) is a life-threatening emergency endocrine condition. Thyroid hormones should be normalized before thyroidectomy is performed in patients with Graves’ disease. However, thyroid hormone levels are inevitably high in patients undergoing surgery. This study analyzed differences in vital sign changes during
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Thyroid storm (TS) is a life-threatening emergency endocrine condition. Thyroid hormones should be normalized before thyroidectomy is performed in patients with Graves’ disease. However, thyroid hormone levels are inevitably high in patients undergoing surgery. This study analyzed differences in vital sign changes during thyroidectomy between patients with controlled and uncontrolled Graves’ disease and assessed thyroid hormone cutoffs for TS. Preoperative levels of the thyroid hormones free T4 (FT4), T3, and thyroid stimulating hormone (TSH) were retrospectively analyzed in patients who underwent total thyroidectomy for Graves’ disease. Patients were divided into those with uncontrolled Graves’ (UG) disease, defined as preoperative TSH <0.3 µIU/mL and FT4 >1.7 ng/dL, those with controlled Graves’ (CG) disease, those with extremely uncontrolled Graves’ (EUG) disease, defined as TSH <0.3 µIU/mL and FT4 >3.4 ng/dL, and finally, those without EUG (non-EUG). The 29 patients with Graves’ disease included 12 with CG group and 17 with UG. FT4 and T3 concentrations were significantly higher in the UG group. There were no differences in vital sign and anesthetic agent. These 29 patients could also be divided into those with (n = 4) and without EUG (n = 25). The mean age was lower (21.5 vs. 40.9 years, p < 0.001) and the mean operation time was shorter (121.4 vs. 208.8 min, p = 0.003) in the EUG group. Requirements for anesthetic agents were greater in the EUG group. Mean FT4 concentration in the EUG group was 3.8 ng/dL, and there were no changes in vital signs during surgery. Vital sign change during thyroid surgery was not observed in patients with uncontrolled Graves’ disease up to the twice upper normal limit of T4 level. Full article
(This article belongs to the Section Immunology)
Open AccessReview The Importance of Time to Prostate-Specific Antigen (PSA) Nadir after Primary Androgen Deprivation Therapy in Hormone-Naïve Prostate Cancer Patients
J. Clin. Med. 2018, 7(12), 565; https://doi.org/10.3390/jcm7120565
Received: 26 November 2018 / Revised: 8 December 2018 / Accepted: 18 December 2018 / Published: 18 December 2018
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Abstract
Prostate-specific antigen (PSA) is currently the most useful biomarker for detection of prostate cancer (PCa). The ability to measure serum PSA levels has affected all aspects of PCa management over the past two decades. The standard initial systemic therapy for advanced PCa is
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Prostate-specific antigen (PSA) is currently the most useful biomarker for detection of prostate cancer (PCa). The ability to measure serum PSA levels has affected all aspects of PCa management over the past two decades. The standard initial systemic therapy for advanced PCa is androgen-deprivation therapy (ADT). Although PCa patients with metastatic disease initially respond well to ADT, they often progress to castration-resistant prostate cancer (CRPC), which has a high mortality rate. We have demonstrated that time to PSA nadir (TTN) after primary ADT is an important early predictor of overall survival and progression-free survival for advanced PCa patients. In in vivo experiments, we demonstrated that the presence of fibroblasts in the PCa tumor microenvironment can prolong the period for serum PSA decline after ADT, and enhance the efficacy of ADT. Clarification of the mechanisms that affect TTN after ADT could be useful to guide selection of optimal PCa treatment strategies. In this review, we discuss recent in vitro and in vivo findings concerning the involvement of stromal–epithelial interactions in the biological mechanism of TTN after ADT to support the novel concept of “tumor regulating fibroblasts”. Full article
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Open AccessArticle Hospitalization Length after Myocardial Infarction: Risk-Assessment-Based Time of Hospital Discharge vs. Real Life Practice
J. Clin. Med. 2018, 7(12), 564; https://doi.org/10.3390/jcm7120564
Received: 7 December 2018 / Accepted: 15 December 2018 / Published: 18 December 2018
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Abstract
According to guidelines, it is safe for low-risk patients with myocardial infarction (MI) to be discharged within 72 h of hospitalization. However, results coming from registries show that the hospital stay is often much longer in a real-life situation. Data on the length
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According to guidelines, it is safe for low-risk patients with myocardial infarction (MI) to be discharged within 72 h of hospitalization. However, results coming from registries show that the hospital stay is often much longer in a real-life situation. Data on the length of the hospital stay (LOS) of MI patients in Polish centers are lacking. We enrolled 212 consecutive patients with acute MI. Low-risk patients were defined according to PAMI II criteria: age <70 years, left ventricular ejection fraction (LVEF) >45%, no persistent ventricular arrhythmia, and no multi-vessel disease (MVD). The median of the hospitalization length was eight days (Q1: 6; Q3: 9). In low-risk patients (25%), the median of LOS was six days (Q1: 5; Q3: 7) (p < 0.001). In a logistic regression analysis patients age, LVEF, ST-segment-elevation MI and the presence of MVD were independent predictors of longer hospitals stay (≥8 days). During follow up, there were no significant differences in the rates of clinical events between patients with shorter (<8 days) and longer (≥8 days) hospitalization. In a real-life situation, the LOS, even in low-risk patients is much longer than recommended in the guidelines. Full article
(This article belongs to the Special Issue Cardiovascular and Neurological Emergency)
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Open AccessArticle Discovery of Potential Plant-Derived Peptide Deformylase (PDF) Inhibitors for Multidrug-Resistant Bacteria Using Computational Studies
J. Clin. Med. 2018, 7(12), 563; https://doi.org/10.3390/jcm7120563
Received: 3 December 2018 / Revised: 11 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
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Abstract
Bacterial peptide deformylase (PDF) is an attractive target for developing novel inhibitors against several types of multidrug-resistant bacteria. The objective of the current study is to retrieve potential phytochemicals as prospective drugs against Staphylococcus aureus peptide deformylase (SaPDF). The current study focuses on
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Bacterial peptide deformylase (PDF) is an attractive target for developing novel inhibitors against several types of multidrug-resistant bacteria. The objective of the current study is to retrieve potential phytochemicals as prospective drugs against Staphylococcus aureus peptide deformylase (SaPDF). The current study focuses on applying ligand-based pharmacophore model (PharmL) and receptor-based pharmacophore (PharmR) approaches. Utilizing 20 known active compounds, pharmL was built and validated using Fischer’s randomization, test set method and the decoy set method. PharmR was generated from the knowledge imparted by the Interaction Generation protocol implemented on the Discovery Studio (DS) v4.5 and was validated using the decoy set that was employed for pharmL. The selection of pharmR was performed based upon the selectivity score and further utilizing the Pharmacophore Comparison module available on the DS. Subsequently, the validated pharmacophore models were escalated for Taiwan Indigenous Plants (TIP) database screening and furthermore, a drug-like evaluation was performed. Molecular docking was initiated for the resultant compounds, employing CDOCKER (available on the DS) and GOLD. Eventually, the stability of the final PDF–hit complexes was affirmed using molecular dynamics (MD) simulation conducted by GROMACS v5.0.6. The redeemed hits demonstrated a similar binding mode and stable intermolecular interactions with the key residues, as determined by no aberrant behaviour for 30 ns. Taken together, it can be stated that the hits can act as putative scaffolds against SaPDF, with a higher therapeutic value. Furthermore, they can act as fundamental structures for designing new drug candidates. Full article
(This article belongs to the Special Issue Advances in Antibacterial Drug Discovery and Therapy)
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Open AccessArticle Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients
J. Clin. Med. 2018, 7(12), 562; https://doi.org/10.3390/jcm7120562
Received: 27 November 2018 / Revised: 12 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
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Abstract
A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to
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A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI ≤ 25.0 kg/m², n confirmed to be appropriate = 74), overweight (BMI > 25.0 ≤ 30.0 kg/m², n = 242) and obese (BMI > 30.0 kg/m², n = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; p = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; p = 0.014) and obese patients (38/150; 25.3%; p = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; p = 0.019) and obese patients (37/150; 24.7%; p = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; p = 0.010) and obese patients (3/150; 2.0% p = 0.027). In total, 60/466; 12.9% patients were diagnosed with non-alcoholic steatohepatitis (NASH). The rate of NASH was higher in lean (14/74; 18.9% p = 0.01) and obese (26/150; 17.3%; p = 0.007) compared to overweight patients (20/242; 8.3%)). Among lean patients, fasting glucose, INR and use of thyroid hormone replacement therapy were independent predictors of NASH in a multivariate model. Lean NAFLD patients were characterized by a severe histological picture similar to obese patients but are more progressed compared to overweight patients. Fasting glucose, international normalized ratio (INR) and the use of thyroid hormone replacement may serve as indicators for NASH in lean patients. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessArticle Effect of High-Intensity Interval Training Combined with L-Citrulline Supplementation on Functional Capacities and Muscle Function in Dynapenic-Obese Older Adults
J. Clin. Med. 2018, 7(12), 561; https://doi.org/10.3390/jcm7120561
Received: 5 November 2018 / Revised: 11 December 2018 / Accepted: 12 December 2018 / Published: 17 December 2018
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Abstract
Background: To compare the effects of high-intensity interval training (HIIT) alone vs. HIIT combined with L-citrulline (CIT) supplementation on functional capacity and muscle function in dynapenic-obese elderly. Methods: A total of 56 obese (fat mass: men > 25%, women > 35%) and dynapenic
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Background: To compare the effects of high-intensity interval training (HIIT) alone vs. HIIT combined with L-citrulline (CIT) supplementation on functional capacity and muscle function in dynapenic-obese elderly. Methods: A total of 56 obese (fat mass: men > 25%, women > 35%) and dynapenic (grip strength/body weight: women < 0.44, men < 0.61) subjects were recruited and divided in two groups: HIIT+CIT (n = 26; age: 6 5 ± four years) vs. HIIT+Placebo (PLA, n = 30; age: 68 ± four years). Participants followed a 12-week HIIT using an elliptical trainer. Participants took a single and isocaloric 10 g-dose of CIT or PLA every day. Body composition; functional and aerobic capacities; absolute or relative upper and lower limbs muscle strength, muscle power; and energy balance were measured pre and post intervention. Results: Both groups significantly improved functional capacity and muscle function. However, HIIT+CIT demonstrated greater improvements in fast-paced Timed Up & Go (p = 0.04) and upper limbs muscle strength (absolute and relative) (p = 0.05) than HIIT+Placebo. Conclusion: CIT supplementation when combined with HIIT seems to induce greater improvements in upper limbs muscle strength and walking speed in dynapenic-obese elderly. Further studies are needed to confirm our results, to elucidate the mechanisms underlying the beneficial effects of CIT and to define the long-term impact of CIT/HIIT. Full article
(This article belongs to the Special Issue Sarcopenia in Older Adults)
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Open AccessArticle Pre-Operative Frailty Status Is Associated with Cardiac Rehabilitation Completion: A Retrospective Cohort Study
J. Clin. Med. 2018, 7(12), 560; https://doi.org/10.3390/jcm7120560
Received: 9 November 2018 / Revised: 12 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
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Abstract
While previous investigations have demonstrated the benefit of cardiac rehabilitation (CR) on outcomes after cardiac surgery, the association between pre-operative frailty and post-operative CR completion is unclear. The purpose of this retrospective cohort study was to determine if pre-operative frailty scores impacted CR
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While previous investigations have demonstrated the benefit of cardiac rehabilitation (CR) on outcomes after cardiac surgery, the association between pre-operative frailty and post-operative CR completion is unclear. The purpose of this retrospective cohort study was to determine if pre-operative frailty scores impacted CR completion post-operatively and if CR completion influenced frailty scores in 114 cardiac surgery patients. Frailty was assessed with the use of the Clinical Frailty Scale (CFS), the Modified Fried Criteria (MFC), the Short Physical Performance Battery (SPPB), and the Functional Frailty Index (FFI). A Mann-Whitney test was used to compare frailty scores between CR completers and non-completers and changes in frailty scores from baseline to 1-year post-operation. CR non-completers were more frail than CR completers at pre-operative baseline based on the CFS (p = 0.01), MFC (p < 0.001), SPPB (p = 0.007), and the FFI (p < 0.001). A change in frailty scores from baseline to 1-year post-operation was not detected in either group using any of the four frailty assessments. However, greater improvements from baseline to 1-year post-operation in two MFC domains (cognitive impairment and low physical activity) and the physical domain of the FFI were found in CR completers as compared to CR non-completers. These data suggest that pre-operative frailty assessments have the potential to identify participants who are less likely to attend and complete CR. The data also suggest that frailty assessment tools need further refinement, as physical domains of frailty function appear to be more sensitive to change following CR than other domains of frailty. Full article
(This article belongs to the Special Issue Cardiac Rehabilitation)
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Open AccessArticle 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis
J. Clin. Med. 2018, 7(12), 559; https://doi.org/10.3390/jcm7120559
Received: 13 November 2018 / Revised: 10 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
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Abstract
Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with
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Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial 18F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUVmax), average SUVmean (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient. Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results. Conclusions: Pretreatment volume-based 18F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study. Full article
(This article belongs to the Section Pulmonology)
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Open AccessArticle Fibroblast Growth Factor 23 to Alpha-Klotho Index Correlates with Systemic Sclerosis Activity: A Proposal for Novel Disease Activity Marker
J. Clin. Med. 2018, 7(12), 558; https://doi.org/10.3390/jcm7120558
Received: 2 November 2018 / Revised: 10 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
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Abstract
Systemic sclerosis, a connective tissue disease, is characterized by thickening of the skin, massive fibrosis of internal organs, vasculopathy, and immune system functioning aberration. Recently, vitamin D (VD) deficit, seen almost universally in patients with systemic sclerosis (SSc), has gained much attention. VD
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Systemic sclerosis, a connective tissue disease, is characterized by thickening of the skin, massive fibrosis of internal organs, vasculopathy, and immune system functioning aberration. Recently, vitamin D (VD) deficit, seen almost universally in patients with systemic sclerosis (SSc), has gained much attention. VD metabolism is precisely orchestrated at the level of the kidney by regulators: parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) and their receptors with a FGF23 co-receptor—α-Klotho. The aim of this study was to assess the levels of VD, α-Klotho, FGF23 in SSc patients and to find the relationship between those parameters and disease activity. We enrolled 48 SSc patients with a diffuse variant of SSc and 23 sex- and age-matched healthy volunteers that served as the control group (CG). Patients were characterized by lower level of VD in comparison to CG (19.8 (12.6–28.9) vs. 24.5 (21.3–31.5) ng/mL; p < 0.01), significantly reduced levels of iFGF23 (19.3 (12.1–30.5) vs. 73.9 (59.7–110.2) pg/mL p < 0.001), and similar α-Klotho concentrations (1415 ± 557 vs. 1526 ± 397 pg/mL), respective. None of these parameters correlated with the extent of skin involvement (modified Rodnan Skin Score) and disease activity according to Eustar 2017 guidelines. The FGF23/α-Klotho index was significantly reduced in SSc patients (0.013 (0.0081–0.025) vs. 0.055 (0.038–0.095); p < 0.001), and its log10 correlated (r = 0.35; p < 0.001) with disease activity score (Eular2017). Our data showed that the FGF23/α-Klotho index may be considered as a novel, potential marker of systemic sclerosis activity. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessArticle N-Terminal Pro-Brain Natriuretic Peptide Predicts Long-Term Technique Failure in Patients Undergoing Peritoneal Dialysis
J. Clin. Med. 2018, 7(12), 557; https://doi.org/10.3390/jcm7120557
Received: 24 November 2018 / Revised: 6 December 2018 / Accepted: 13 December 2018 / Published: 16 December 2018
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It is unclear whether N-terminal pro-brain type natriuretic peptide (NT-proBNP) level can be a biomarker for technique failure among long-term peritoneal dialysis (PD) patients. We prospectively included end-stage renal disease patients undergoing PD from a single center between December 2011 and December 2017.
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It is unclear whether N-terminal pro-brain type natriuretic peptide (NT-proBNP) level can be a biomarker for technique failure among long-term peritoneal dialysis (PD) patients. We prospectively included end-stage renal disease patients undergoing PD from a single center between December 2011 and December 2017. We divided the cohort into high or low NT-proBNP groups and analyzed the risk factors associated with the incidence of technique failure using Cox proportional hazard regression analysis. A total of 258 chronic PD patients (serum NT-proBNP, 582 ± 1216 ng/mL) were included. After a mean follow-up of 3.6 years, 49.6% of PD patients developed technique failure and switched to hemodialysis, while 15.5% died. Cox proportional hazard regression analyses accounting for age, gender, diabetes, renal clearance, C-reactive protein, and hydration status, showed that higher natural log transformed NT-proBNP levels (hazard ratio [HR] 1.13, p < 0.01) were predictive of an increased risk of technique failure, and were also predictive of an increased risk of mortality (HR 1.56, p < 0.01). Consequently, NT-proBNP might be an under-recognized biomarker for estimating the risk of technique failure, and regular monitoring NT-proBNP levels among PD patients may assist in their care. Full article
(This article belongs to the Section Nephrology & Urology)
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Open AccessArticle A Systematic Review, Meta-Analysis, and Meta-Regression Evaluating the Efficacy and Mechanisms of Action of Probiotics and Synbiotics in the Prevention of Surgical Site Infections and Surgery-Related Complications
J. Clin. Med. 2018, 7(12), 556; https://doi.org/10.3390/jcm7120556
Received: 10 November 2018 / Revised: 5 December 2018 / Accepted: 13 December 2018 / Published: 16 December 2018
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Intestinal microbiota play an important role in the pathogenesis of surgical site infections (SSIs) and other surgery-related complications (SRCs). Probiotics and synbiotics were found to lower the risk of surgical infections and other surgery-related adverse events. We systematically reviewed the approach based on
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Intestinal microbiota play an important role in the pathogenesis of surgical site infections (SSIs) and other surgery-related complications (SRCs). Probiotics and synbiotics were found to lower the risk of surgical infections and other surgery-related adverse events. We systematically reviewed the approach based on the administration of probiotics and synbiotics to diminish SSIs/SRCs rates in patients undergoing various surgical treatments and to determine the mechanisms responsible for their effectiveness. A systematic literature search in PubMed/MEDLINE/Cochrane Central Register of Controlled Trials from the inception of databases to June 2018 for trials in patients undergoing surgery supplemented with pre/pro/synbiotics and randomized to the intervention versus placebo/no treatment and reporting on primarily: (i) putative mechanisms of probiotic/symbiotic action, and secondarily (ii) SSIs and SRCs outcomes. Random-effect model meta-analysis and meta-regression analysis of outcomes was done. Thirty-five trials comprising 3028 adult patients were included; interventions were probiotics (n = 16) and synbiotics (n = 19 trials). We found that C-reactive protein (CRP) and Interleukin-6 (IL-6) were significantly decreased (SMD: −0.40, 95% CI [−0.79, −0.02], p = 0.041; SMD: −0.41, 95% CI [−0.70, −0.02], p = 0.006, respectively) while concentration of acetic, butyric, and propionic acids were elevated in patients supplemented with probiotics (SMD: 1.78, 95% CI [0.80, 2.76], p = 0.0004; SMD: 0.67, 95% CI [0.37, −0.97], p = 0.00001; SMD: 0.46, 95% CI [0.18, 0.73], p = 0.001, respectively). Meta-analysis confirmed that pro- and synbiotics supplementation was associated with significant reduction in the incidence of SRCs including abdominal distention, diarrhea, pneumonia, sepsis, surgery site infection (including superficial incisional), and urinary tract infection, as well as the duration of antibiotic therapy, duration of postoperative pyrexia, time of fluid introduction, solid diet, and duration of hospital stay (p < 0.05). Probiotics and synbiotics administration counteract SSIs/SRCs via modulating gut-immune response and production of short chain fatty acids. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Small Bowel Disorders)
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Open AccessReview Biobanking Organoids or Ground-State Stem Cells?
J. Clin. Med. 2018, 7(12), 555; https://doi.org/10.3390/jcm7120555
Received: 12 November 2018 / Revised: 5 December 2018 / Accepted: 13 December 2018 / Published: 16 December 2018
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Abstract
Autologous transplantation of human epidermal stem cells cultured in Green’s method is one of the first examples of utilizing adult stem cells in regenerative medicine. Using the same method, we cloned p63-expressing distal airway stem cells and showed their essential role in lung
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Autologous transplantation of human epidermal stem cells cultured in Green’s method is one of the first examples of utilizing adult stem cells in regenerative medicine. Using the same method, we cloned p63-expressing distal airway stem cells and showed their essential role in lung regeneration in a mouse model of acute respiratory distress syndrome. However, adult stem cells of columnar epithelial tissues had until recently evaded all attempts at cloning. To address this issue, we developed a novel technology that enabled cloning ground-state stem cells of the columnar epithelium. The adaption of this technology to clone stem cells of cancer precursors furthered our understanding of the dynamics of processes such as clonal evolution and dominance in Barrett’s esophagus, as well as for testing platforms for chemical screening. Taken together, the properties of these ground-state stem cells, including unlimited propagation, genomic stability, and regio-specificity, make them ideal for regenerative medicine, disease modeling and drug discovery. Full article
(This article belongs to the Special Issue Biobanking and Regenerative Medicine)
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Open AccessArticle One-Year Progression and Risk Factors for the Development of Chronic Kidney Disease in Septic Shock Patients with Acute Kidney Injury: A Single-Centre Retrospective Cohort Study
J. Clin. Med. 2018, 7(12), 554; https://doi.org/10.3390/jcm7120554
Received: 16 November 2018 / Revised: 12 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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Abstract
(1) Background: Sepsis-associated acute kidney injury (AKI) can lead to permanent kidney damage, although the long-term prognosis in patients with septic shock remains unclear. This study aimed to identify risk factors for the development of chronic kidney disease (CKD) in septic shock patients
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(1) Background: Sepsis-associated acute kidney injury (AKI) can lead to permanent kidney damage, although the long-term prognosis in patients with septic shock remains unclear. This study aimed to identify risk factors for the development of chronic kidney disease (CKD) in septic shock patients with AKI. (2) Methods: A single-site, retrospective cohort study was conducted using a registry of adult septic shock patients. Data from patients who had developed AKI between January 2011 and April 2017 were extracted, and 1-year follow-up data were analysed to identify patients who developed CKD. (3) Results: Among 2208 patients with septic shock, 839 (38%) had AKI on admission (stage 1: 163 (19%), stage 2: 339 (40%), stage 3: 337 (40%)). After one year, kidney function had recovered in 27% of patients, and 6% had progressed to CKD. In patients with stage 1 AKI, 10% developed CKD, and mortality was 13% at one year; in patients with stage 2 and 3 AKI, the CKD rate was 6%, and the mortality rate was 42% and 47%, respectively. Old age, female, diabetes, low haemoglobin levels and a high creatinine level at discharge were seen to be risk factors for the development of CKD. (4) Conclusions: AKI severity correlated with mortality, but it did not correlate with the development of CKD, and patients progressed to CKD, even when initial AKI stage was not severe. Physicians should focus on the recovery of renal function, and ensure the careful follow-up of patients with risk factors for the development of CKD. Full article
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Open AccessArticle Health-Related Quality of Life in Chronic Liver Diseases: A Strong Impact of Hand Grip Strength
J. Clin. Med. 2018, 7(12), 553; https://doi.org/10.3390/jcm7120553
Received: 8 November 2018 / Revised: 12 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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We sought to examine the influence of hand grip strength (HGS) and skeletal muscle mass (SMM) on the health-related quality of life (H-QOL) as evaluated by the 36-Item Short-Form Health Survey (SF-36) questionnaire in chronic liver diseases (CLDs, 198 men and 191 women).
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We sought to examine the influence of hand grip strength (HGS) and skeletal muscle mass (SMM) on the health-related quality of life (H-QOL) as evaluated by the 36-Item Short-Form Health Survey (SF-36) questionnaire in chronic liver diseases (CLDs, 198 men and 191 women). Decreased HGS was defined as HGS <26 kg for men and <18 kg for women. Decreased SMM was defined as SMM index <7.0 kg/m2 for men and <5.7 kg/m2 for women, using bioimpedance analysis. SF-36 scores were compared between groups stratified by HGS or SMM. Between-group differences (decreased HGS vs. non-decreased HGS) in the items of physical functioning (PF), role physical (RP), bodily pain, vitality (VT), social functioning (SF), role emotional (RE), and physical component summary score (PCS) reached significance, while between-group differences (decreased SMM vs. non-decreased SMM) in the items of PF, SF and RE were significant. Multivariate analyses revealed that HGS was significantly linked to PF (p = 0.0031), RP (p = 0.0185), and PCS (p = 0.0421) in males, and PF (p = 0.0034), VT (p = 0.0150), RE (p = 0.0422), and PCS (p = 0.0191) in females. HGS had a strong influence especially in the physiological domains in SF-36 in CLDs. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessReview Fetal Toxicity of Immunosuppressive Drugs in Pregnancy
J. Clin. Med. 2018, 7(12), 552; https://doi.org/10.3390/jcm7120552
Received: 30 October 2018 / Revised: 5 December 2018 / Accepted: 11 December 2018 / Published: 15 December 2018
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Abstract
Women affected by autoimmune diseases, organ transplantation, or neoplasia need to continue immunosuppressive treatment during pregnancy. In this setting, not only a careful planning of pregnancy, but also the choice of drugs is critical to preventing maternal complications and minimizing the fetal risks.
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Women affected by autoimmune diseases, organ transplantation, or neoplasia need to continue immunosuppressive treatment during pregnancy. In this setting, not only a careful planning of pregnancy, but also the choice of drugs is critical to preventing maternal complications and minimizing the fetal risks. Some immunosuppressive drugs are teratogenic and should be replaced even before the pregnancy, while other drugs need to be managed with caution to prevent fetal risks, including miscarriage, intrauterine growth restriction, prematurity, and low birth weight. In particular, the increasing use of biologic agents raises the question of their compatibility with reproduction. In this review we present data on the indication and safety in pregnancy of the most frequently used immunosuppressive drugs. Full article
Open AccessArticle Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches
J. Clin. Med. 2018, 7(12), 551; https://doi.org/10.3390/jcm7120551
Received: 26 November 2018 / Revised: 11 December 2018 / Accepted: 11 December 2018 / Published: 15 December 2018
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Abstract
Cervical cancer is regarded as one of the major burdens noticed in women next to breast cancer. Although, human papilloma viruses (HPVs) are regarded as the principal causative agents, they require certain other factors such as oestrogen hormone to induce cervical cancer. Aromatase
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Cervical cancer is regarded as one of the major burdens noticed in women next to breast cancer. Although, human papilloma viruses (HPVs) are regarded as the principal causative agents, they require certain other factors such as oestrogen hormone to induce cervical cancer. Aromatase is an enzyme that converts androgens into oestrogens and hindering this enzyme could subsequently hamper the formation of oestrogen thereby alleviating the disease. Accordingly, in the current investigation, a structure based pharmacophore was generated considering two proteins bearing the Protein Data Bank (PDB) codes 3EQM (pharm 1) and 3S7S (pharm 2), respectively. The two models were employed as the 3D query to screen the in-house built natural compounds database. The obtained 51 compounds were escalated to molecular docking studies to decipher on the binding affinities and to predict the quintessential binding modes which were affirmed by molecular dynamics (MD) simulations. The compound has induced dose-dependent down regulation of PP2B, Nitric oxide synthase-2 (NOS2), and Interleukin 6 (IL-6) genes in the HeLa cells and has modulated the expression of apoptotic genes such as Bax, Bcl2, and caspases-3 at different concentrations. These results guide us to comprehend that the identified aromatase inhibitor was effective against the cervical cancer cells and additionally could server as scaffolds in designing new drugs. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessArticle Effect of New-Onset Diabetes Mellitus on Renal Outcomes and Mortality in Patients with Chronic Kidney Disease
J. Clin. Med. 2018, 7(12), 550; https://doi.org/10.3390/jcm7120550
Received: 23 November 2018 / Revised: 12 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Background: The incidence rates of diabetes mellitus (DM) and chronic kidney disease (CKD) are increasing worldwide and their coexistence can have a large negative impact on clinical outcomes. However, it is unclear how incident DM affects CKD patients. Methods: Incident CKD patients between
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Background: The incidence rates of diabetes mellitus (DM) and chronic kidney disease (CKD) are increasing worldwide and their coexistence can have a large negative impact on clinical outcomes. However, it is unclear how incident DM affects CKD patients. Methods: Incident CKD patients between 2000 and 2013 were identified from the National Health Insurance Research Database of Taiwan; they were classified as non-DM (n = 10,356), pre-existing DM (n = 6982), and incident DM (n = 1103). Non-DM cases were patients who did not develop DM before the end of the observation period. The outcomes of interest were end-stage renal disease (ESRD), mortality, and composite outcome (ESRD or death). The association between the DM groups and clinical outcomes was estimated using the inverse probability of group-weighted (IPW) multivariate-adjusted time-dependent Cox regression models. Results: During the study period of 14 years, 1735 (16.6%) patients in the non-DM group reached ESRD compared with 2168 (31.05%) in the pre-existing DM group and 111 (11.03%) in the incident DM group (p < 0.001). Moreover, 2219 (21.43%) patients in the non-DM group died compared with 1895 (27.14%) in the pre-existing DM group and 303 (27.47%) in the incident DM group (p < 0.001). Compared with the non-DM group, the pre-existing DM group was associated with a higher risk of ESRD [hazard ratio (HR) 2.54; 95% confidence interval (CI 2.43–2.65), death (HR 2.23; 95% CI 2.14–2.33), and a composite outcome (HR 2.29; 95% CI 2.21–2.36). Similarly, incident DM was also associated with a higher risk of ESRD (HR 1.12; 95% CI 1.06–1.19), death (HR 2.48; 95% CI 2.37–2.60), and a composite outcome (HR 1.77; 95% CI 1.70–1.84) compared with the non-DM group. Factors contributing to incident DM included old age, low monthly income, and having hypertension, hyperlipidemia, and ischemic heart disease, while pentoxifylline reduced the risk of incident DM. Conclusion: Similarly to pre-existing DM, CKD patients with incident DM carried a higher risk of ESRD, mortality, and a composite outcome compared with those with non-DM. For those at risk of incident DM, strict monitoring and intervention strategies must be adopted to help improve their clinical outcomes. Full article
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Open AccessReview Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence
J. Clin. Med. 2018, 7(12), 549; https://doi.org/10.3390/jcm7120549
Received: 16 November 2018 / Revised: 9 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed,
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The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, including the following key words: “testosterone”, “androgens”, “inflammatory cytokines”, “inflammatory biomarkers” with focus on clinical studies as well as basic scientific studies in human and animal models. Significant benefits of testosterone therapy in ameliorating or attenuating the symptoms of several chronic inflammatory diseases were reported. Because anti–tumor necrosis factor therapy is the mainstay for the treatment of moderate-to-severe inflammatory bowel disease; including Crohn’s disease and ulcerative colitis, and because testosterone therapy in hypogonadal men with chronic inflammatory conditions reduce tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6, we suggest that testosterone therapy attenuates the inflammatory process and reduces the burden of disease by mechanisms inhibiting inflammatory cytokine expression and function. Mechanistically, androgens regulate the expression and function of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and CRP (C-reactive protein). Here, we suggest that testosterone regulates multiple and overlapping cellular and molecular pathways involving a host of immune cells and biochemical factors that converge to contribute to attenuation of the inflammatory process. Full article
(This article belongs to the Special Issue Testosterone and Men’s Health: From Evidence to Clinical Practice)
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Open AccessArticle Hyperbaric Oxygen Therapy Enhanced Circulating Levels of Endothelial Progenitor Cells and Angiogenesis Biomarkers, Blood Flow, in Ischemic Areas in Patients with Peripheral Arterial Occlusive Disease
J. Clin. Med. 2018, 7(12), 548; https://doi.org/10.3390/jcm7120548
Received: 14 November 2018 / Revised: 6 December 2018 / Accepted: 10 December 2018 / Published: 14 December 2018
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Background: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Methods: In total, 57 consecutive patients
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Background: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Methods: In total, 57 consecutive patients with PAOD undergoing the HBO therapy (3 atmospheres (atm) for 2 h each time) were prospectively enrolled into the present study. Venous blood sampling was performed to assess the circulating levels of EPCs and soluble angiogenesis factors prior to and during five sessions of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow in ischemic areas, was measured by moorVMS-PRES. Results: The results demonstrated that the circulating levels of EPCs (cluster of differentiation (CD)34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors—vascular endothelial growth factor/stromal cell-derived factor 1/hepatocyte growth factor/fibroblast growth factor (VEGF/SDF-1α/HGF/FGF) were significantly increased post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Additionally, Matrigel assay showed that the angiogenesis was significantly increased in post-HBO therapy as compared to prior to therapy (p < 0.001). Furthermore, SPP was significantly increased in the ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Importantly, the HBO therapy did appear to result in complications, and all the patients were uneventfully discharged without amputation. Conclusions: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area. Full article
(This article belongs to the Section Vascular Medicine)
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Open AccessArticle Prediction of Technical Difficulties in Laparoscopic Splenectomy and Analysis of Risk Factors for Postoperative Complications in 468 Cases
J. Clin. Med. 2018, 7(12), 547; https://doi.org/10.3390/jcm7120547
Received: 21 November 2018 / Revised: 9 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Prediction of intraoperative difficulties may be helpful in planning surgery; however, few studies explored this issue in laparoscopic splenectomy (LS). We performed retrospective analysis of consecutive 468 patients undergoing LS from 1998 to 2017 (295 women; median age 47 years). The patients were
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Prediction of intraoperative difficulties may be helpful in planning surgery; however, few studies explored this issue in laparoscopic splenectomy (LS). We performed retrospective analysis of consecutive 468 patients undergoing LS from 1998 to 2017 (295 women; median age 47 years). The patients were divided into difficult LS and control groups. The inclusion criteria for difficult LS were operative time ≥mean + 2SD; intraoperative blood loss ≥500 mL, intraoperative adverse events (IAE), conversion. Primary outcomes were risk factors for difficult splenectomy and secondary outcomes for perioperative morbidity. Fifty-six patients were included in the difficult LS group (12%). Spleens ≥19 cm and higher participation of younger surgeons in consecutive years were predictive for difficult splenectomy. Age ≥53 years and diagnosis other than idiopathic thrombocytopenic purpura (ITP) were independent risk factors of spleen ≥19 cm. The perioperative morbidity was 8.33%; its OR was increased only by blood loss and IAEs. Only blood loss significantly increased serious morbidity. Male sex, spleens ≥19 cm, and IAEs were independent risk factors for intraoperative hemorrhage. Spleen length ≥19 cm was a risk factor for difficult LS and intraoperative hemorrhage. Diagnoses other than ITP in patients aged ≥53 years with ≥19 cm spleens are predictive for intraoperative difficulties and perioperative complications. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
Open AccessArticle Effect of Methotrexate in the Treatment of Distal Interphalangeal Joint Extensor Tendon Enthesopathy in Patients with Nail Psoriasis
J. Clin. Med. 2018, 7(12), 546; https://doi.org/10.3390/jcm7120546
Received: 12 November 2018 / Revised: 6 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
To assess the effect of methotrexate on the development of distal interphalangeal joint extensor tendon enthesopathy in psoriasis, thirty-two people aged 34 to 57 years with nail psoriasis and distal interphalangeal joint extensor tendon enthesopathy (19 patients with Ps (psoriasis) and 13 with
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To assess the effect of methotrexate on the development of distal interphalangeal joint extensor tendon enthesopathy in psoriasis, thirty-two people aged 34 to 57 years with nail psoriasis and distal interphalangeal joint extensor tendon enthesopathy (19 patients with Ps (psoriasis) and 13 with PsA (psoriatic arthritis) were started on methotrexate at 15 to 25 mg/week and the treatment was continued for 6 months). A total of 319 nails were examined. After six months of treatment, the thicknesses of the nail plate, nail bed and nail matrix were found to decrease in both groups of patients. Methotrexate treatment resulted in a decrease in the joint extensor tendon thickness only in patients with Ps (0.94 ± 0.05 vs. 0.96 ± 0.04, p < 0.001), where the tendon thickness after treatment correlated with the matrix thickness (r = 0.337, p = 0.018) and with the bed thickness (r = 0.299, p = 0.039). Methotrexate treatment resulted in a decrease in the extensor tendon thickness only in patients with Ps but not in PsA. The findings of this study may suggest the effectiveness of systemic treatment of nail psoriasis in patients without arthritis and the use of US nail examinations in Ps and PsA patients in morphological change assessment and response to treatment. Full article
(This article belongs to the Section Dermatology)
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Open AccessArticle Driving Cessation and Cognitive Dysfunction in Patients with Mild Cognitive Impairment
J. Clin. Med. 2018, 7(12), 545; https://doi.org/10.3390/jcm7120545
Received: 21 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
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Abstract
Although driving by adults with cognitive impairment is an important public health concern, little is known about the indicators of driving cessation in patients with mild cognitive impairment (MCI). We aimed to investigate the prevalence of driving cessation in patients with MCI and
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Although driving by adults with cognitive impairment is an important public health concern, little is known about the indicators of driving cessation in patients with mild cognitive impairment (MCI). We aimed to investigate the prevalence of driving cessation in patients with MCI and the predictive value of cognitive performances for driving cessation. Patients with MCI were recruited in the Seoul National University Bundang Hospital; they met following inclusion criteria. Age range of 51–80 years, Clinical Dementia Rating scale score of 0.5, and ever car drivers including former and current drivers. All participants underwent comprehensive standardized cognitive assessments and information on driving status was obtained via an interview using a systematic questionnaire. The median age of the 135 participants was 72 years, and 54 participants (40%) were women; 93 patients (68.9%) were current drivers and 42 (31.1%) were former drivers. In univariate analysis, former drivers showed poorer performances in digit span backward and categorical fluency tests than current drivers. In multivariate logistic regression analysis, a poor digit span backward test score was significantly related with driving cessation (odds ratio: 0.493, 95% confidence interval: 0.258–0.939). In patients with MCI, poor performance in the digit span backward test, which represents impaired working memory capacity, was associated with a higher probability of driving cessation. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
Open AccessReview Current Research and New Perspectives of Telemedicine in Chronic Heart Failure: Narrative Review and Points of Interest for the Clinician
J. Clin. Med. 2018, 7(12), 544; https://doi.org/10.3390/jcm7120544
Received: 20 November 2018 / Revised: 7 December 2018 / Accepted: 10 December 2018 / Published: 13 December 2018
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Background: This is a narrative review of both the literature and Internet pertaining to telemedicine projects within the field of heart failure, with special attention placed on remote monitoring of second-generation projects and trials, particularly in France. Results: Since the beginning of the
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Background: This is a narrative review of both the literature and Internet pertaining to telemedicine projects within the field of heart failure, with special attention placed on remote monitoring of second-generation projects and trials, particularly in France. Results: Since the beginning of the 2000’s, several telemedicine projects and trials focused on chronic heart failure have been developed. The first telemedicine projects (e.g., TEN-HMS, BEAT-HF, Tele-HF, and TIM-HF) primarily investigated telemonitoring or for the older ones, telephone follow-up. Numerous second-generation telemedicine projects have emerged in Europe over the last ten years or are still under development for computer science heart failure, especially in Europe, such as SCAD, OSICAT, E-care, PRADO-INCADO, and TIM-HF2. The E-care telemonitoring project fits within the telemedicine 2.0 framework, based on connected objects, new information and communication technologies (ICT) and Web 2.0 technologies. E-care is the first telemedicine project including artificial intelligence (AI). TIM-HF2 is the first positive prospective randomized study with regards to EBM with positive significant clinical benefit, in terms of unplanned cardiovascular hospital admissions and all-cause deaths. The potential contribution of second-generation telemedicine projects in terms of mortality, morbidity, and number of hospitalizations avoided is currently under study. Their impact in terms of health economics is likewise being investigated, taking into account that the economic and social benefits brought up by telemedicine solutions were previously validated by the original telemedicine projects. Full article
(This article belongs to the Special Issue The Future of Artificial Intelligence in Clinical Medicine)
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Open AccessReview Examining the Association and Directionality between Mental Health Disorders and Substance Use among Adolescents and Young Adults in the U.S. and Canada—A Systematic Review and Meta-Analysis
J. Clin. Med. 2018, 7(12), 543; https://doi.org/10.3390/jcm7120543
Received: 17 November 2018 / Revised: 5 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
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Abstract
Background: The purpose of this systematic review was to examine the association and directionality between mental health disorders and substance use among adolescents and young adults in the U.S. and Canada. Methods: The following databases were used: Medline, PubMed, Embase, PsycINFO, and Cochrane
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Background: The purpose of this systematic review was to examine the association and directionality between mental health disorders and substance use among adolescents and young adults in the U.S. and Canada. Methods: The following databases were used: Medline, PubMed, Embase, PsycINFO, and Cochrane Library. Meta-analysis used odds ratios as the pooled measure of effect. Results: A total of 3656 studies were screened and 36 were selected. Pooled results showed a positive association between depression and use of alcohol (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.24–1.83), cannabis (OR = 1.29, 95% CI: 1.10–1.51), and tobacco (OR = 1.65, 95% CI: 1.43–1.92). Significant associations were also found between anxiety and use of alcohol (OR = 1.54, 95% CI: 1.19–2.00), cannabis (OR = 1.36, 95% CI: 1.02–1.81), and tobacco (OR = 2.21, 95% CI: 1.54–3.17). A bidirectional relationship was observed with tobacco use at baseline leading to depression at follow-up (OR = 1.87, CI = 1.23–2.85) and depression at baseline leading to tobacco use at follow-up (OR = 1.22, CI = 1.09–1.37). A unidirectional relationship was also observed with cannabis use leading to depression (OR = 1.33, CI = 1.19–1.49). Conclusion: This study offers insights into the association and directionality between mental health disorders and substance use among adolescents and young adults. Our findings can help guide key stakeholders in making recommendations for interventions, policy and programming. Full article
(This article belongs to the Section Pathergasiology & Psychology)
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Open AccessArticle Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials
J. Clin. Med. 2018, 7(12), 542; https://doi.org/10.3390/jcm7120542
Received: 15 November 2018 / Revised: 30 November 2018 / Accepted: 8 December 2018 / Published: 12 December 2018
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Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint
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Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p < 0.001 and HR 0.77, p < 0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p < 0.012), with the exception of melanoma (in women, HR 0.80, p = 0.006). PFS was longer in men than in women (HR 0.67, p < 0.001 and HR 0.77, p = 0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle Tarsal Tunnel Mechanosensitivity Is Increased in Patients with Asthma: A Case-Control Study
J. Clin. Med. 2018, 7(12), 541; https://doi.org/10.3390/jcm7120541
Received: 11 November 2018 / Revised: 23 November 2018 / Accepted: 10 December 2018 / Published: 12 December 2018
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Background: Based on changes in lung function and musculoskeletal disorders in patients with asthma, this study aimed to compare the tarsal tunnel and fibular bone pressure pain thresholds (PPTs) of patients with asthma and healthy matched-paired controls. Methods: A case-control study was performed.
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Background: Based on changes in lung function and musculoskeletal disorders in patients with asthma, this study aimed to compare the tarsal tunnel and fibular bone pressure pain thresholds (PPTs) of patients with asthma and healthy matched-paired controls. Methods: A case-control study was performed. One hundred participants were recruited: 50 asthma patients and 50 healthy matched-paired controls. Bilaterally, tarsal tunnel and fibula bone PPTs were registered. Results: Statistically significant differences (p < 0.01) were shown bilaterally for tarsal tunnel PPT. With the exception of fibula PPT (p > 0.05), asthma patients presented less tarsal tunnel PPT than healthy participants. Statistically significant differences (p < 0.05) were shown for two linear regression prediction models of the right (R2 = 0.279) and left (R2 = 0.249) tarsal tunnels PPTs as dependent variables, and based on sex, group, contralateral tarsal tunnel PPT and ipsilateral fibula PPT as independent variables. Conclusions: The study findings showed that a bilateral tarsal tunnel mechanosensitivity increase is exhibited in patients diagnosed with asthma. The presence of asthma may bilaterally predict the PPT of tarsal tunnel. These findings may suggest the presence of central sensitization in asthma patients, which could clinically predispose them to musculoskeletal disorders, such as tarsal tunnel syndrome. Full article
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Open AccessArticle Utility of Novel Cardiorenal Biomarkers in the Prediction and Early Detection of Congestive Kidney Injury Following Cardiac Surgery
J. Clin. Med. 2018, 7(12), 540; https://doi.org/10.3390/jcm7120540
Received: 12 November 2018 / Revised: 7 December 2018 / Accepted: 10 December 2018 / Published: 12 December 2018
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Abstract
Acute Kidney Injury (AKI) in the context of right ventricular failure (RVF) is thought to be largely congestive in nature. This study assessed the utility of biomarkers high sensitivity cardiac troponin T (hs-cTnT), N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL)
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Acute Kidney Injury (AKI) in the context of right ventricular failure (RVF) is thought to be largely congestive in nature. This study assessed the utility of biomarkers high sensitivity cardiac troponin T (hs-cTnT), N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL) for prediction and early detection of congestive AKI (c-AKI) following cardiac surgery. This prospective nested case-control study recruited 350 consecutive patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. Cases were patients who developed (1) AKI (2) new or worsening RVF, or (3) c-AKI. Controls were patients free of these complications. Biomarker levels were measured at baseline after anesthesia induction and immediately postoperatively. Patients with c-AKI had increased mean duration of mechanical ventilation and length of stay in hospital and in the intensive care unit (p < 0.01). For prediction of c-AKI, baseline NT-proBNP yielded an area under the curve (AUC) of 0.74 (95% CI, 0.60–0.89). For early detection of c-AKI, postoperative NT-proBNP yielded an AUC of 0.78 (0.66–0.91), postoperative hs-cTnT yielded an AUC of 0.75 (0.58–0.92), and ∆hs-cTnT yielded an AUC of 0.80 (0.64–0.96). The addition of baseline creatinine to ∆hs-cTnT improved the AUC to 0.87 (0.76–0.99), and addition of diabetes improved the AUC to 0.93 (0.88–0.99). Δhs-cTnT alone, or in combination with baseline creatinine or diabetes, detects c-AKI with high accuracy following cardiac surgery. Full article
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Open AccessArticle Association between Hemoglobin and Hemoglobin A1c: A Data-Driven Analysis of Health Checkup Data in Japan
J. Clin. Med. 2018, 7(12), 539; https://doi.org/10.3390/jcm7120539
Received: 14 November 2018 / Revised: 5 December 2018 / Accepted: 11 December 2018 / Published: 12 December 2018
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Background: Interpretation of hemoglobin A1c (HbA1c) levels may be confounded by spurious results in anemic persons, but its degree is not well-established. Methods: We used an employer-based health insurance database, containing health checkup data and medical claims data; both were
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Background: Interpretation of hemoglobin A1c (HbA1c) levels may be confounded by spurious results in anemic persons, but its degree is not well-established. Methods: We used an employer-based health insurance database, containing health checkup data and medical claims data; both were linked via a unique identifier of each beneficiary. This study included persons aged 18–75 years who participated in health checkups, with a confirmed or suspected diagnosis of diabetes. The relationship between hemoglobin (Hb) and HbA1c is shown in a spline curve using a machine learning technique accounting for patient factors and within-person correlations. Spline curves were also shown in several sub-populations. Results: Overall, a decreased Hb value was associated with a lower HbA1c value, but the extent differed among populations. In the whole cohort of the type-2 diabetes group (55,420 persons), the curve was generally a plateau in the persons with a Hb value <120–130 g/L. Among the 18,478 persons with HbA1c around 48 mmol/mol, we observed a liner trend. Among the current glucose-lowering medication users (6253 persons), we found a right upward curve. Conclusions: The relationship between Hb and HbA1c may not be straightforward, varying among populations of different clinical interest. Our results indicate that a simple formulation between the Hb and HbA1c values is unlikely. Full article
(This article belongs to the Section Hematology)
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Open AccessArticle Comparison of Clinical Manifestations, Antimicrobial Susceptibility Patterns, and Mutations of Fluoroquinolone Target Genes between Elizabethkingia meningoseptica and Elizabethkingia anophelis Isolated in Taiwan
J. Clin. Med. 2018, 7(12), 538; https://doi.org/10.3390/jcm7120538
Received: 19 November 2018 / Revised: 8 December 2018 / Accepted: 10 December 2018 / Published: 11 December 2018
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Elizabethkingia meningoseptica and Elizabethkingia anophelis are two major pathogens in the genus Elizabethkingia. Studies have revealed that Elizabethkingia anophelis is frequently misidentified as E. meningoseptica. Therefore, our aim was to explore the clinical and molecular differences between these two species. The
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Elizabethkingia meningoseptica and Elizabethkingia anophelis are two major pathogens in the genus Elizabethkingia. Studies have revealed that Elizabethkingia anophelis is frequently misidentified as E. meningoseptica. Therefore, our aim was to explore the clinical and molecular differences between these two species. The database of a clinical microbiology laboratory in a university-affiliated hospital of Taiwan was searched to identify patients with Elizabethkingia infections between January 2005 and June 2018. Species were reidentified using 16S ribosomal RNA gene sequencing. Twenty E. meningoseptica and 72 E. anophelis samples were collected from consecutive patients. E. meningoseptica was significantly more frequently isolated from the cerebrospinal fluid than was E. anophelis. The most susceptible antibiotic for all Elizabethkingia isolates was minocycline (91.3%), followed by levofloxacin (52.2%), tigecycline (23.9%), and piperacillin tazobactam (23.9%). Compared with E. anophelis, E. meningoseptica was significantly less susceptible to piperacillin tazobactam, minocycline, and levofloxacin. Regarding nonsynonymous substitutions in the quinolone-resistance determining regions of DNA gyrase, six sites were recognized in E. meningoseptica and one site was recognized in E. anophelis. E. meningoseptica had a significantly higher rate of fluoroquinolone target gene mutations than did E. anophelis. Because of less susceptibility to multiple antibiotics than E. anophelis, empirical antimicrobial therapy of E. meningoseptica should be more rigorous. Full article
(This article belongs to the Section Microbiology & Parasitology)
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J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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