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J. Clin. Med., Volume 8, Issue 4 (April 2019)

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Cover Story (view full-size image) Cardiomyopathy is a group of heterogeneous cardiac diseases that impair systolic and diastolic [...] Read more.
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Open AccessArticle
Renal Failure Impact on the Outcomes of ST-Segment Elevation Myocardial Infarction Patients Due to a Left Main Coronary Culprit Lesion Treated Using a Primary Percutaneous Coronary Intervention
J. Clin. Med. 2019, 8(4), 565; https://doi.org/10.3390/jcm8040565
Received: 8 April 2019 / Revised: 22 April 2019 / Accepted: 24 April 2019 / Published: 25 April 2019
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Abstract
Background: Patients with ST-segment elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (PPCI) on a left main culprit lesion have very high mortality rates. The interaction of chronic kidney disease (CKD) with such a catastrophic acute event on the background of their [...] Read more.
Background: Patients with ST-segment elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (PPCI) on a left main culprit lesion have very high mortality rates. The interaction of chronic kidney disease (CKD) with such a catastrophic acute event on the background of their highly complex atherosclerotic lesions is not well established. Therefore, we sought to evaluate in these patients the influence of the estimated glomerular filtration rate (eGFR) on short- and long-term mortality. Methods: We retrospectively analyzed renal function in 81 patients with STEMI and PPCI on a left main culprit lesion from two tertiary centers. Results: Patients were divided in two groups according to an eGFR cut-off of 60 mL/min/1.73 m2: 40 patients with CKD and 41 without CKD. Patients with renal failure were older, had more diabetes, and had experienced more frequent myocardial infarction MIs. CKD patients had a higher baseline-SYNTAX score (p = 0.015), higher residual-SYNTAX score (p < 0.001), and lower SYNTAX revascularization index-SRI (p = 0.003). Mortality at 30-day, 1-year, and 3-year follow-ups were not significantly different between the two groups. However, when analyzed as a continuous variable, eGFR emerged as a predictor of 1-year mortality, both in univariate analysis (OR = 0.97, 95% CI: 0.95–0.99, p = 0.005) and in multivariate analysis, after adjusting for cardiogenic shock and Thrombolysis in Myocardial Infarction TIMI 0/1 flow (OR = 0.975, 95% CI: 0.95–0.99, p = 0.021). Conclusions: In STEMI with PPCI on a left main culprit lesion, renal failure was associated with more complex coronary lesions and less complete revascularization, and turned out to be an independent predictor of mortality at 1-year follow-up. Full article
(This article belongs to the Section Cardiology)
Open AccessArticle
A Threshold of Objectively-Assessed Daily Sedentary Time for All-Cause Mortality in Older Adults: A Meta-Regression of Prospective Cohort Studies
J. Clin. Med. 2019, 8(4), 564; https://doi.org/10.3390/jcm8040564
Received: 18 March 2019 / Revised: 18 April 2019 / Accepted: 19 April 2019 / Published: 25 April 2019
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Abstract
Background: This meta-analysis aimed to estimate the shape of the dose-response association between objectively-assessed daily sedentary time (ST) and all-cause mortality, and to explore whether there is a threshold of ST above which there is an increase in mortality risk in older adults. [...] Read more.
Background: This meta-analysis aimed to estimate the shape of the dose-response association between objectively-assessed daily sedentary time (ST) and all-cause mortality, and to explore whether there is a threshold of ST above which there is an increase in mortality risk in older adults. Methods: Searches for prospective cohort studies providing effect estimates of daily ST (exposure) on all-cause mortality (outcome) were undertaken in five databases up to 31 March 2019. A random-effects meta-regression model was conducted to quantify the dose-response relationship between daily ST and all-cause mortality. Sensitivity analyses were also performed to test the stability of the results. Results: Our analysis of pooled data from 11 eligible studies did not reveal a consistent shape of association between ST and mortality. After excluding three studies with potential confounding bias, there was a log-linear dose-response relationship between daily ST and all-cause mortality. Overall, higher amounts of time spent in sedentary behaviors were associated with elevated mortality risks in older adults. Visual assessments of dose-response relationships based on meta-regression analyses indicated that increased mortality risks became significant when total ST exceeded approximately 9 h/day. Conclusions: Based on a limited number of studies, this meta-analysis provides a starting point for considering a cut-off of daily sedentary time, suggesting older adults spend less time in daily sitting. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessReview
Acid-Base Disturbances in Patients with Asthma: A Literature Review and Comments on Their Pathophysiology
J. Clin. Med. 2019, 8(4), 563; https://doi.org/10.3390/jcm8040563
Received: 27 March 2019 / Revised: 19 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
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Abstract
Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the [...] Read more.
Asthma is a common illness throughout the world that affects the respiratory system function, i.e., a system whose operational adequacy determines the respiratory gases exchange. It is therefore expected that acute severe asthma will be associated with respiratory acid-base disorders. In addition, the resulting hypoxemia along with the circulatory compromise due to heart–lung interactions can reduce tissue oxygenation, with a particular impact on respiratory muscles that have increased energy needs due to the increased workload. Thus, anaerobic metabolism may ensue, leading to lactic acidosis. Additionally, chronic hypocapnia in asthma can cause a compensatory drop in plasma bicarbonate concentration, resulting in non-anion gap acidosis. Indeed, studies have shown that in acute severe asthma, metabolic acid-base disorders may occur, i.e., high anion gap or non-anion gap metabolic acidosis. This review briefly presents studies that have investigated acid-base disorders in asthma, with comments on their underlying pathophysiology. Full article
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Open AccessArticle
Maintenance Negative Pressure Ventilation Improves Survival in COPD Patients with Exercise Desaturation
J. Clin. Med. 2019, 8(4), 562; https://doi.org/10.3390/jcm8040562
Received: 16 April 2019 / Revised: 21 April 2019 / Accepted: 22 April 2019 / Published: 25 April 2019
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Abstract
Negative pressure ventilation (NPV), when used as an adjuvant to pulmonary rehabilitation, improves lung function, increases exercise capacity, and reduces exacerbations. The aim of this study was to determine whether maintenance NPV improves long-term clinical outcomes and reduces mortality in patients with chronic [...] Read more.
Negative pressure ventilation (NPV), when used as an adjuvant to pulmonary rehabilitation, improves lung function, increases exercise capacity, and reduces exacerbations. The aim of this study was to determine whether maintenance NPV improves long-term clinical outcomes and reduces mortality in patients with chronic obstructive pulmonary disease (COPD). Between 2003 and 2009, 341 patients were treated for COPD either with or without hospital-based NPV. We measured forced expiratory volume in one second (FEV1), 6-min walking distance (6MWD), and oxygen saturation by pulse oximetry (SpO2) during a 6-min walk test (6MWT) every 3–6 months. Desaturation (D) during the 6MWT was defined as a reduction in SpO2 of ≥10% from baseline. The NPV group had a better survival outcome than the Non-NPV group. The 8-year survival probabilities for the NPV and Non-NPV groups were 60% and 20%, respectively (p < 0.01). Baseline desaturation was a significant risk factor for death, and the risk of death increased with desaturation severity (SpO2 80~89: hazard ratios (HR) 2.7, 95% confidence interval (CI) 1.4–5.3; SpO2 < 80: HR 3.1, 95% CI 1.3–7.4). The NPV group had a slower decline in lung function and 6MWD. The NPV + D and Non-NPV+D had a threefold and fourfold increase in the risks of all-cause mortality compared with the NPV-ND, respectively. Maintenance non-invasive NPV reduced long-term mortality in COPD patients. The desaturating COPD patients had an increased mortality risk compared with non-desaturating COPD patients. Full article
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Open AccessArticle
Environment and Male Fertility: Effects of Benzo-α-Pyrene and Resveratrol on Human Sperm Function In Vitro
J. Clin. Med. 2019, 8(4), 561; https://doi.org/10.3390/jcm8040561
Received: 13 March 2019 / Revised: 12 April 2019 / Accepted: 19 April 2019 / Published: 25 April 2019
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Abstract
Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed [...] Read more.
Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed whether resveratrol (RES), an AHR antagonist and antioxidant molecule, had any protective effect. To accomplish this, 30 normozoospermic, healthy, non-smoker men not exposed to BaP were enrolled. Spermatozoa of 15 men were incubated with increasing concentrations of BaP to evaluate its effect and to establish its dose response. Then, spermatozoa of the 15 other men were incubated with BaP (15 µM/mL), chosen according to the dose-response and/or RES to evaluate its antagonistic effects. The effects of both substances were evaluated after 3 h of incubation on total and progressive sperm motility and on the following bio-functional sperm parameters evaluated by flow cytometry: Degree of chromatin compactness, viability, phosphatidylserine externalization (PS), late apoptosis, mitochondrial membrane potential (MMP), DNA fragmentation, degree of lipoperoxidation (LP), and concentrations of mitochondrial superoxide anion. Benzo-α-pyrene decreased total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipoperoxidation and mitochondrial superoxide anion levels. All these effects were statistically significant at the lowest concentration tested (15 µM/mL) and they were confirmed at the concentration of 45 µM/mL. In turn, RES was able to counteract the detrimental effects of BaP on sperm motility, abnormal chromatin compactness, lipid peroxidation, and mitochondrial superoxide. This study showed that BaP alters sperm motility and bio-functional sperm parameters and that RES exerts a protective effect on BaP-induced sperm damage. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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Open AccessArticle
UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition
J. Clin. Med. 2019, 8(4), 560; https://doi.org/10.3390/jcm8040560
Received: 27 March 2019 / Revised: 11 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
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Abstract
CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been [...] Read more.
CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer. Full article
(This article belongs to the Section Molecular Medicine)
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Open AccessReview
Biomarkers in the Diagnosis, Management, and Prognostication of Perioperative Right Ventricular Failure in Cardiac Surgery—Are We There Yet?
J. Clin. Med. 2019, 8(4), 559; https://doi.org/10.3390/jcm8040559
Received: 23 February 2019 / Revised: 27 March 2019 / Accepted: 22 April 2019 / Published: 25 April 2019
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Abstract
Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few [...] Read more.
Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few studies have examined the use of biomarkers in RVF, and even fewer have examined their utility in the perioperative setting of patients undergoing cardiac surgery. Of the available classes of biomarkers, this review focuses on biomarkers of (1) inflammation and (2) myocyte injury/stress, due to their superior potential in perioperative RV assessment, including Galectin 3, ST2/sST2, CRP, cTN/hs-cTn, and BNP/NT-proBNP. This review was performed to help highlight the importance of perioperative RV function in patients undergoing cardiac surgery, to review the current modalities of RV assessment, and to provide a review of RV specific biomarkers and their potential utilization in the clinical and perioperative setting in cardiac surgery. Based on current evidence, we suggest the potential utility of ST2, sST2, Gal-3, CRP, hs-cTn, and NT-proBNP in predicting and detecting RVF in cardiac surgery patients, as they encompass the multifaceted nature of perioperative RVF and warrant further investigation to establish their clinical utility. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
Open AccessArticle
Mismatch Repair/Microsatellite Instability Testing Practices among US Physicians Treating Patients with Advanced/Metastatic Colorectal Cancer
J. Clin. Med. 2019, 8(4), 558; https://doi.org/10.3390/jcm8040558
Received: 18 March 2019 / Revised: 16 April 2019 / Accepted: 19 April 2019 / Published: 24 April 2019
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Abstract
The study objective was to assess US physicians’ Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. [...] Read more.
The study objective was to assess US physicians’ Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. Eligible physicians were US-based with at least 5 years of experience treating CRC patients, had at least one mCRC patient in their routine care in the past 6 months, and had ordered at least one MMR/MSI test for CRC in the past 6 months. Descriptive and logistic regression analyses were performed. Awareness of specific MMR/MSI testing guidelines was high (n = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of National Comprehensive Cancer Network (NCCN) guidelines. Universal testing for all CRC patients was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively order the test for some CRC patients. Key barriers for testing included insufficient tissue sample (48.3%, 73/151), patient declined to have the test done (35.8%, 54/151) and insurance cost concerns for patients (31.1%, 47/151), while 27.2% (41/151) reported no barriers. The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle
Is Pelvic Plexus Block Superior to Periprostatic Nerve Block for Pain Control during Transrectal Ultrasonography-Guided Prostate Biopsy? A Double-Blind, Randomized Controlled Trial
J. Clin. Med. 2019, 8(4), 557; https://doi.org/10.3390/jcm8040557
Received: 19 April 2019 / Accepted: 23 April 2019 / Published: 24 April 2019
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Abstract
We evaluated whether pelvic plexus block (PPB) is superior to periprostatic nerve block (PNB) for pain control during transrectal ultrasonography (TRUS)-guided prostate biopsy (PBx). A prospective, double-blind, randomized, controlled study was performed at a single center; 46 patients were enrolled and randomly allocated [...] Read more.
We evaluated whether pelvic plexus block (PPB) is superior to periprostatic nerve block (PNB) for pain control during transrectal ultrasonography (TRUS)-guided prostate biopsy (PBx). A prospective, double-blind, randomized, controlled study was performed at a single center; 46 patients were enrolled and randomly allocated into two groups: PPB (n = 23) and PNB (n = 23). The visual analogue scale (VAS) was used; pain scores were measured four times: during local anesthesia, probe insertion, sampling procedures, and at 15 min post procedures. No significant differences were observed in VAS scores during local anesthesia (2.30 for PPB vs. 2.65 for PNB, p = 0.537) or during probe insertion (2.83 for PPB vs. 2.39 for PNB, p = 0.569). Similarly, no differences in VAS scores were detected during the sampling procedures (2.83 for PPB vs. 2.87 for PNB, p = 0.867) and at 15 min post procedures (1.39 for PPB vs. 1.26 for PNB, p = 0.631). No major complications were noted in either group. Both PPB and PNB are comparably effective and safe methods for PBx related pain relief, and PPB is not superior to PNB. Local anesthetic method could be selected based on the preference and skill of the operator. Full article
(This article belongs to the Section Nephrology & Urology)
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Open AccessReview
Prevention of Sudden Death Related to Sport: The Science of Basic Life Support—From Theory to Practice
J. Clin. Med. 2019, 8(4), 556; https://doi.org/10.3390/jcm8040556
Received: 17 March 2019 / Revised: 17 April 2019 / Accepted: 19 April 2019 / Published: 24 April 2019
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Abstract
The sudden cardiac arrest (CA) and death of athletes are dramatic and emotionally impacting events for health professionals, family, and society. Although the practice of sport participation improves general health, physical fitness, and quality of life, intense physical exercise can be a trigger [...] Read more.
The sudden cardiac arrest (CA) and death of athletes are dramatic and emotionally impacting events for health professionals, family, and society. Although the practice of sport participation improves general health, physical fitness, and quality of life, intense physical exercise can be a trigger for CA and sudden death occasionally in the presence of known or unknown cardiac disorders (mainly hypertrophic cardiomyopathy) and risk factors (environment, health style, family, and genetic). The present review found that sudden death associated with CA was not such a common event in competitive athletes, but it might be an underestimated event in recreational athletes. Thus, considering the exponential increase in sport participation, both in a recreational or competitive way, and the rate of sudden CA, knowledge of implementing prevention and treatment strategies is crucial. This includes preparation of health professionals and lay people in basic life support (BLS); screening and pre-participation assessment in sport programs and health education; and promotion for the recognition of CA and early completion of BLS and rapid access to automatic external defibrillator to improve the victim survival/prognosis. Thus, the purpose of this review is to provide for health professionals and lay people the most updated information, based on current guidelines, of how to proceed in an emergency situation associated with sudden CA of young adult athletes. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessReview
Patient Experience in Home Respiratory Therapies: Where We Are and Where to Go
J. Clin. Med. 2019, 8(4), 555; https://doi.org/10.3390/jcm8040555
Received: 5 March 2019 / Revised: 22 April 2019 / Accepted: 23 April 2019 / Published: 24 April 2019
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Abstract
The increasing number of patients receiving home respiratory therapy (HRT) is imposing a major impact on routine clinical care and healthcare system sustainability. The current challenge is to continue to guarantee access to HRT while maintaining the quality of care. The patient experience [...] Read more.
The increasing number of patients receiving home respiratory therapy (HRT) is imposing a major impact on routine clinical care and healthcare system sustainability. The current challenge is to continue to guarantee access to HRT while maintaining the quality of care. The patient experience is a cornerstone of high-quality healthcare and an emergent area of clinical research. This review approaches the assessment of the patient experience in the context of HRT while highlighting the European contribution to this body of knowledge. This review demonstrates that research in this area is still limited, with no example of a prescription model that incorporates the patient experience as an outcome and no specific patient-reported experience measures (PREMs) available. This work also shows that Europe is leading the research on HRT provision. The development of a specific PREM and the integration of PREMs into the assessment of prescription models should be clinical research priorities in the next several years. Full article
(This article belongs to the Special Issue Clinical Medicine for Healthcare and Sustainability)
Open AccessReview
Effectiveness and Safety of Direct Oral Anticoagulants versus Vitamin K Antagonists for People Aged 75 Years and over with Atrial Fibrillation: A Systematic Review and Meta-Analyses of Observational Studies
J. Clin. Med. 2019, 8(4), 554; https://doi.org/10.3390/jcm8040554
Received: 7 March 2019 / Revised: 18 April 2019 / Accepted: 18 April 2019 / Published: 24 April 2019
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Abstract
Older people, are underrepresented in randomised controlled trials of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to combine data from observational studies to provide evidence for the treatment of people aged ≥75 years. [...] Read more.
Older people, are underrepresented in randomised controlled trials of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to combine data from observational studies to provide evidence for the treatment of people aged ≥75 years. Medline, Embase, Scopus and Web of Science were searched. The primary effectiveness outcome was ischaemic stroke. Safety outcomes were major bleeding, intracranial haemorrhage, gastrointestinal bleeding, myocardial infarction, and mortality. Twenty-two studies were eligible for inclusion. Two studies related specifically to people ≥75 years but were excluded from meta-analysis due to low quality; all data in the meta-analyses were from subgroups. The pooled risk estimate of ischaemic stroke was slightly lower for DOACs. There was no significant difference in major bleeding, mortality, or myocardial infarction. Risk of intracranial haemorrhage was 44% lower with DOACs, but risk of GI bleeding was 46% higher. Our results suggest that DOACs may be preferable for the majority of older patients with AF, provided they are not at significant risk of a GI bleed. However, these results are based entirely on data from subgroup analyses so should be interpreted cautiously. There is a need for adequately powered research in this patient group. Full article
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Open AccessArticle
Analgesic Effect of Low Dose Nefopam Hydrochloride after Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial
J. Clin. Med. 2019, 8(4), 553; https://doi.org/10.3390/jcm8040553
Received: 24 March 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 24 April 2019
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Abstract
Arthroscopic rotator cuff repair causes acute postoperative hyperalgesia. Multimodal analgesia is preferable to opioid-based intravenous patient-controlled analgesia (IV-PCA) due to postoperative nausea and vomiting (PONV). We evaluated the effect of nefopam as a postoperative non-opioid analgesic after shoulder surgeries. A total of 180 [...] Read more.
Arthroscopic rotator cuff repair causes acute postoperative hyperalgesia. Multimodal analgesia is preferable to opioid-based intravenous patient-controlled analgesia (IV-PCA) due to postoperative nausea and vomiting (PONV). We evaluated the effect of nefopam as a postoperative non-opioid analgesic after shoulder surgeries. A total of 180 adult patients were enrolled for arthroscopic rotator cuff repair. They were randomly assigned to nefopam (N) or control (C) groups and each group was reclassified according to the interscalene block (B) into NB, CB and NX, CX. Nefopam was applied at a constant dose intravenously during recovery. Pain scores were measured with a Visual Analogue Scale (VAS) before (T0), immediately after (T1), 30 min (T2) and 12 h (T3), 24 h (T4) and 48 h (T5) after surgery. There was no significant difference in demographic data. The overall VAS scores did not differ with regard to nefopam use, except for the NB group at T4 in intention to treat (ITT) analysis (p < 0.05). PONV occurred more frequently in the N group than in the C group (p < 0.05). Neither individual nor all risk factors were associated with PONV occurrence (p > 0.10). In conclusion, nefopam alone did not show a definite decrease in postoperative pain. It instead increased PONV regardless of risk factors. Full article
(This article belongs to the Section Anesthesiology)
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Open AccessArticle
Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis
J. Clin. Med. 2019, 8(4), 552; https://doi.org/10.3390/jcm8040552
Received: 27 March 2019 / Revised: 16 April 2019 / Accepted: 18 April 2019 / Published: 24 April 2019
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Abstract
Aortic valve sclerosis (AVSc) is characterized by non-uniform thickening of the leaflets without hemodynamic changes. Endothelial dysfunction, also caused by dysregulation of glutathione homeostasis expressed as ratio between its reduced (GSH) and its oxidised form (GSSG), could represent one of the pathogenic triggers [...] Read more.
Aortic valve sclerosis (AVSc) is characterized by non-uniform thickening of the leaflets without hemodynamic changes. Endothelial dysfunction, also caused by dysregulation of glutathione homeostasis expressed as ratio between its reduced (GSH) and its oxidised form (GSSG), could represent one of the pathogenic triggers of AVSc. We prospectively enrolled 58 patients with overt atherosclerosis and requiring coronary artery bypass grafting (CABG). The incidence of AVSc in the studied population was 50%. The two groups (No-AVSc and AVSc) had similar clinical characteristics. Pre-operatively, AVSc group showed significantly lower GSH/GSSG ratio than No-AVSc group (p = 0.02). Asymmetric dimethylarginine (ADMA) concentration was significantly higher in AVSc patients compared to No-AVSc patients (p < 0.0001). Explanted sclerotic aortic valves presented a significantly increased protein glutathionylation (Pr-SSG) than No-AVSc ones (p = 0.01). In vitro, inhibition of glutathione reductase caused β-actin glutathionylation, activation of histone 2AX, upregulation of α2 smooth muscle actin (ACTA2), downregulation of platelet and endothelial cell adhesion molecule 1 (PECAM1) and cadherin 5 (CDH5). In this study, we showed for the first time that the dysregulation of glutathione homeostasis is associated with AVSc. We found that Pr-SSG is increased in AVSc leaflets and it could lead to EndMT via DNA damage. Further studies are warranted to elucidate the causal role of Pr-SSG in aortic valve degeneration. Full article
(This article belongs to the Section Vascular Medicine)
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Open AccessReview
Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis
J. Clin. Med. 2019, 8(4), 551; https://doi.org/10.3390/jcm8040551
Received: 23 March 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 23 April 2019
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Abstract
The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic [...] Read more.
The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2–78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0–88.0%), unsteady gait (58%; 48.2–67.8%), and weakness (43%; 33.1–52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9–83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 <150 pmol/L (70.7%; 60.7–80.8%), homocysteine >15 µmol/L (90.3%; 79.3–100%), and methylmalonic acid >0.4 µmol/L (93.8%; 80.4–100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessArticle
Median Arcuate Ligament Compression in Orthotopic Liver Transplantation: Results from a Single-Center Analysis and a European Survey Study
J. Clin. Med. 2019, 8(4), 550; https://doi.org/10.3390/jcm8040550
Received: 21 March 2019 / Revised: 15 April 2019 / Accepted: 22 April 2019 / Published: 23 April 2019
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Abstract
Median arcuate ligament compression (MALC) potentially causes arterial complications in orthotopic liver transplantation (OLT). Here we aimed to investigate the incidence of MALC and its impact on clinical outcome after OLT. In addition, we performed an international survey among 52 European liver transplant [...] Read more.
Median arcuate ligament compression (MALC) potentially causes arterial complications in orthotopic liver transplantation (OLT). Here we aimed to investigate the incidence of MALC and its impact on clinical outcome after OLT. In addition, we performed an international survey among 52 European liver transplant centers to explore local protocols on the management of these patients. Data of 286 consecutive OLT recipients from a prospective database were analyzed retrospectively (05/2010-07/2017). Preoperative computed-tomography images were evaluated. Celiac axis stenosis due to MALC was found in 34 patients (12%). Intrinsic stenosis was present in 16 (6%) patients. Twenty-six patients (77%) with MALC underwent standard arterial revascularization with median arcuate ligament (MAL)-division. Patients treated for MALC had comparable baseline data and no difference was found in early- and long-term outcome compared to the rest of our cohort. Our survey found heterogeneous strategies regarding diagnosis and treatment of MALC. Only 29% of the centers reported the division of MAL in these patients as routine procedure. Even though there is no consensus on diagnosis and management of MALC among European centers, a surgical division of MAL is feasible and safe and should be considered in OLT recipients with MALC. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessArticle
Identifying Knowledge Gaps among LVAD Candidates
J. Clin. Med. 2019, 8(4), 549; https://doi.org/10.3390/jcm8040549
Received: 31 March 2019 / Revised: 18 April 2019 / Accepted: 22 April 2019 / Published: 23 April 2019
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Abstract
Education is an important aspect of evaluation and consent for left ventricular assist device (LVAD) candidates. A better understanding of candidate knowledge during the education process can help identify knowledge gaps and improve informed consent processes. This paper presents the results from a [...] Read more.
Education is an important aspect of evaluation and consent for left ventricular assist device (LVAD) candidates. A better understanding of candidate knowledge during the education process can help identify knowledge gaps and improve informed consent processes. This paper presents the results from a validated, LVAD-specific Knowledge Scale administered to candidates before and after education to identify items most and least frequently answered correctly. At baseline and 1-week, both candidates educated with a standard education and an LVAD-specific decision aid were most likely to answer logistical items relating to support and self-care correctly with ≥90% of candidates answering these items correctly after education. Candidates were least likely to answer questions about risks, transplant eligibility, and expenses correctly with <60% of candidates answering them correctly after education. Items with the greatest improvement in correct answers from baseline to 1-week were primarily related to the logistics of living with an LVAD. Candidates educated with the decision aid showed significant improvements on more knowledge items including those related to the forecasting of recovery and complications when compared to candidates educated with a standard education. The 20-item scale provides a standardized way for clinicians to identify knowledge gaps with LVAD candidates, potentially helping to tailor education. Targeted improvements in LVAD education should focus on the understanding of risk and potential complications to ensure that decision-making and informed consent processes emphasize both the patient and clinicians’ conceptualizations of knowledge needs for informed consent. Full article
(This article belongs to the Special Issue Clinical Use of Left Ventricular Assist Devices)
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Open AccessArticle
The Role of Laparoscopic Investigation in Enabling Natural Conception and Avoiding in vitro Fertilization Overuse for Infertile Patients of Unidentified Aetiology and Recurrent Implantation Failure Following in vitro Fertilization
J. Clin. Med. 2019, 8(4), 548; https://doi.org/10.3390/jcm8040548
Received: 21 March 2019 / Revised: 18 April 2019 / Accepted: 19 April 2019 / Published: 22 April 2019
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Abstract
The present study aims to explore the effectiveness of laparoscopic surgery on women presenting with infertility, of unidentified aetiology according to the standard infertility investigation, and recurrent failed In Vitro Fertilization (IVF) attempts. Identifying and correcting possible underlying pathologies by laparoscopy may subsequently [...] Read more.
The present study aims to explore the effectiveness of laparoscopic surgery on women presenting with infertility, of unidentified aetiology according to the standard infertility investigation, and recurrent failed In Vitro Fertilization (IVF) attempts. Identifying and correcting possible underlying pathologies by laparoscopy may subsequently enable natural conception in an effort to address infertility and avoid IVF overuse. One-hundred and seven (107) women with unidentified aetiology of infertility and recurrent failed IVF attempts met the inclusion criteria. Laparoscopic surgery was performed as the endpoint of the patients’ diagnostic journey, aiming to identify a possible underlying factor as the cause of infertility. Sixty-two (62) out of 107 patients (57.94%) that underwent laparoscopy were diagnosed with endometriosis, 25 out of the 107 patients (23.3%) were diagnosed with periadnixal and pelvic adhesions, and 20 cases (18.69%) presented with no pathology and remained unexplained. Following identification and correction of endometriosis and pelvic adhesions, patients were invited to conceive naturally. For the patients that laparoscopic investigation failed to reveal any pathology they were categorized as unexplained infertility and were subjected to a single IVF cycle. Natural conception success rate within the first postoperative year was the primary outcome. Within the first postoperative year, 30 out of 62 patients (48.38%) diagnosed with endometriosis following laparoscopic investigation achieved a natural conception, and 28 out of them (93.4%) reported live-births. Additionally, 11 out of 25 patients (44%) diagnosed with periadnixal and pelvic adhesions achieved natural conception within the first operative year. Regarding the group of unexplained infertility patients, only four out of the 20 patients (20%) achieved clinical pregnancy in the first post-operative IVF cycle. In conclusion, laparoscopy appears to be a promising approach, addressing infertility, providing significant diagnostic findings, while avoiding IVF overuse regarding patients of unidentified infertility presenting with recurrent failed IVF attempts. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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Open AccessReview
Does Herpes Zoster Increase the Risk of Stroke and Myocardial Infarction? A Comprehensive Review
J. Clin. Med. 2019, 8(4), 547; https://doi.org/10.3390/jcm8040547
Received: 27 March 2019 / Revised: 11 April 2019 / Accepted: 18 April 2019 / Published: 22 April 2019
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Abstract
Herpes zoster (HZ) caused by varicella zoster virus (VZV) reactivation is characterized as a vesicular rash of unilateral distribution that can also cause multiple complications; such as post-herpetic neuralgia; ophthalmic zoster; and other neurological issues. VZV can also increase incident hemorrhagic or ischemic [...] Read more.
Herpes zoster (HZ) caused by varicella zoster virus (VZV) reactivation is characterized as a vesicular rash of unilateral distribution that can also cause multiple complications; such as post-herpetic neuralgia; ophthalmic zoster; and other neurological issues. VZV can also increase incident hemorrhagic or ischemic complications by causing inflammatory vasculopathy. Thus; emerging epidemiological and clinical data recognizes an association between HZ and subsequent acute strokes or myocardial infarction (MI). This study reviewed published articles to elucidate the association between HZ and cerebrovascular and cardiac events. Individuals exposed to HZ or herpes zoster ophthalmicus had 1.3 to 4-fold increased risks of cerebrovascular events. Higher risks were noted among younger patients (age < 40 years) within one year after an HZ episode. The elevated risk of CV events diminished gradually according to age and length of time after an HZ episode. The putative mechanisms of VZV vasculopathy were also discussed. Several studies showed that the development of herpes zoster and herpes zoster ophthalmicus increased the risks of stroke; transient ischemic attack; and acute cardiac events. The association between VZV infection and cardiovascular events requires further studies to establish the optimal antiviral treatment and zoster vaccination to reduce zoster-associated vascular risk Full article
(This article belongs to the Section Microbiology & Parasitology)
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Open AccessCorrection
Correction: Jiun-Nong Lin; Chung-Hsu Lai; Chih-Hui Yang and Yi-Han Huang. Comparison of Clinical Manifestations, Antimicrobial Susceptibility Patterns, and Mutations of Fluoroquinolone Target Genes between Elizabethkingia meningoseptica and Elizabethkingia anophelis Isolated in Taiwan. Journal of Clinical Medicine 2018, 7, 538
J. Clin. Med. 2019, 8(4), 546; https://doi.org/10.3390/jcm8040546
Received: 19 April 2019 / Accepted: 22 April 2019 / Published: 22 April 2019
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Abstract
The authors wish to make the following corrections to this paper [...] Full article
Open AccessArticle
Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?
J. Clin. Med. 2019, 8(4), 545; https://doi.org/10.3390/jcm8040545
Received: 22 March 2019 / Revised: 18 April 2019 / Accepted: 19 April 2019 / Published: 22 April 2019
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Abstract
The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify [...] Read more.
The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify a biomarker that can predict lymph node status. Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. Although the correlation between TILs and response to chemotherapy was established by previous studies, our retrospective study investigated the correlation between TILs and lymph node status. We analyzed data on 172 patients. According to stage, patients were divided in two groups: patients who underwent primary surgical treatment (breast-conserving or mastectomy and sentinel lymph node (SLN) biopsy +/− axillary clearance in conformity with lymph node status) and patients who received chemotherapy prior to surgical treatment (breast-conserving or mastectomy + axillary clearance). We showed a good inverse correlation between TILs and lymph nodes status for both early stage and locally advanced breast cancers. Moreover, TILs are a predictor for positive lymph nodes in the axilla in patients undergoing axillary clearance after SLN biopsy, with no statistical difference between the intrinsic or histological subtype of breast cancers. We also obtained a significant correlation between TILs and response to chemotherapy with no significative difference according to histological subtype. Although further data have still to be gathered before meeting the criteria for clinical utility, this study demonstrates that TILs are one of the most accredited forthcoming biomarkers for breast cancer (BC) patients. Full article
(This article belongs to the Section Hematology)
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Open AccessArticle
Maternal Cardiovascular Risk Assessment 3-to-11 Years Postpartum in Relation to Previous Occurrence of Pregnancy-Related Complications
J. Clin. Med. 2019, 8(4), 544; https://doi.org/10.3390/jcm8040544
Received: 7 March 2019 / Revised: 4 April 2019 / Accepted: 16 April 2019 / Published: 20 April 2019
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Abstract
The aim of the present study was to assess the long-term outcomes of women 3-to-11 years postpartum in relation to the previous occurrence of pregnancy-related complications such as gestational hypertension (GH), preeclampsia (PE) and fetal growth restriction (FGR). Body mass index (BMI), waist [...] Read more.
The aim of the present study was to assess the long-term outcomes of women 3-to-11 years postpartum in relation to the previous occurrence of pregnancy-related complications such as gestational hypertension (GH), preeclampsia (PE) and fetal growth restriction (FGR). Body mass index (BMI), waist circumference values, the average values of systolic (SBP) and diastolic (DBP) blood pressures and heart rate, total serum cholesterol levels, serum HDL (high-density lipoprotein) cholesterol levels, serum LDL (low-density lipoprotein) cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum CRP (C-reactive protein) levels, plasma homocysteine levels, serum uric acid levels, individual and relative risks of having a heart attack or stroke over the next ten years were compared between groups (50 GH, 102 PE, 34 FGR and 90 normal pregnancies) and correlated with the severity of the disease with regard to clinical signs (25 PE without severe features, 77 PE with severe features), and delivery date (36 early PE, 66 late PE). The adjustment for potential covariates was made, where appropriate. At 3–11 years follow-up women with a history of GH, PE regardless of the severity of the disease and the delivery date, PE without severe features, PE with severe features, early PE, and late PE had higher BMI, waist circumferences, SBP, DBP, and predicted 10-year cardiovascular event risk when compared with women with a history of normotensive term pregnancy. In addition, increased serum levels of uric acid were found in patients previously affected with GH, PE regardless of the severity of the disease and the delivery date, PE with severe features, early PE, and late PE. Higher serum levels of lipoprotein A were found in patients previously affected with early PE. The receiver operating characteristic (ROC) curve analyses were able to identify a substantial proportion of women previously affected with GH or PE with a predisposition to later onset of cardiovascular diseases. Women with a history of GH and PE represent a risky group of patients that may benefit from implementation of early primary prevention strategies. Full article
(This article belongs to the Section Cardiology)
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Open AccessArticle
Association between Interleukin-6 Levels and Perioperative Fatigue in Gastric Adenocarcinoma Patients
J. Clin. Med. 2019, 8(4), 543; https://doi.org/10.3390/jcm8040543
Received: 21 March 2019 / Revised: 12 April 2019 / Accepted: 18 April 2019 / Published: 20 April 2019
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Abstract
Background: Gastric adenocarcinoma (GA), one of the most common gastrointestinal cancers worldwide, is often accompanied by cancer cachexia in the advanced stage owing to malnutrition and cancer-related symptoms. Although resection is the most effective curative procedure for GA patients, it may cause perioperative [...] Read more.
Background: Gastric adenocarcinoma (GA), one of the most common gastrointestinal cancers worldwide, is often accompanied by cancer cachexia in the advanced stage owing to malnutrition and cancer-related symptoms. Although resection is the most effective curative procedure for GA patients, it may cause perioperative fatigue, worsening the extent of cancer cachexia. Although the relationship between cytokines and cancer fatigue has been evaluated, it is unclear which cytokines are associated with fatigue in GA patients. Therefore, this study aimed to investigate whether the changes in cytokine levels were associated with the perioperative changes in fatigue amongst GA patients. Methods: We included GA patients undergoing gastric surgery in a single academic medical center between June 2017 and December 2018. Fatigue-related questionnaires, serum cytokine levels (interferon-gamma, interleukin (IL)-1, IL-2, IL-5, IL-6, IL-12 p70, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor), and biochemistry profiles (albumin, prealbumin, C-reactive protein, and white blood cell counts) were assessed at three time points (preoperative day 0 (POD 0), post-operative day 1 (POD 1), and postoperative day 7 (POD 7)). We used the Brief Fatigue Inventory-Taiwan Form to assess the extent of fatigue. The change in fatigue scores among the three time points, as an independent variable, was adjusted for clinicopathologic characteristics, malnutrition risk, and cancer stages. Results: A total of 34 patients were included for analysis, including 12 female and 22 male patients. The mean age was 68.9 years. The mean score for fatigue on POD 0, POD 1, and POD 7 was 1.7, 6.2, and 3.6, respectively, with significant differences among the three time points (P < 0.001). Among the cytokines, only IL-6 was significantly elevated from POD 0 to POD 1. In the regression model, the change in IL-6 levels between POD 0 and POD 1 (coefficients = 0.01 for every 1 pg/mL increment; 95% confidence interval: 0.01–0.02; P = 0.037) and high malnutrition risk (coefficients = 2.80; 95% confidence interval: 1.45–3.52; P = 0.041) were significantly associated with changes in fatigue scores. Conclusions: The perioperative changes in plasma IL-6 levels are positively associated with changes in the fatigue scores of GA patients undergoing gastric surgery. Targeting the IL-6 signaling cascade or new fatigue-targeting medications may attenuate perioperative fatigue, and further clinical studies should be designed to validate this hypothesis. Full article
(This article belongs to the Special Issue Surgical Management of Gastric Cancer)
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Open AccessArticle
Clinical Significance of Multiparametric Magnetic Resonance Imaging as a Preoperative Predictor of Oncologic Outcome in Very Low-Risk Prostate Cancer
J. Clin. Med. 2019, 8(4), 542; https://doi.org/10.3390/jcm8040542
Received: 22 March 2019 / Revised: 10 April 2019 / Accepted: 18 April 2019 / Published: 19 April 2019
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Abstract
Currently, multiparametric magnetic resonance imaging (mpMRI) is not an indication for patients with very low-risk prostate cancer. In this study, we aimed to evaluate the usefulness of mpMRI as a diagnostic tool in these patients. We retrospectively analyzed the clinical and pathological data [...] Read more.
Currently, multiparametric magnetic resonance imaging (mpMRI) is not an indication for patients with very low-risk prostate cancer. In this study, we aimed to evaluate the usefulness of mpMRI as a diagnostic tool in these patients. We retrospectively analyzed the clinical and pathological data of individuals with very low-risk prostate cancer, according to the NCCN guidelines, who underwent mpMRI before radical prostatectomy at our institution between 2010 and 2016. Patients who did not undergo pre-evaluation with mpMRI were excluded. We analyzed the factors associated with biochemical recurrence (BCR) using Cox regression model, logistic regression analysis, and Kaplan–Meier curve. Of 253 very low-risk prostate cancer patients, we observed 26 (10.3%) with BCR during the follow-up period in this study. The median follow-up from radical prostatectomy was 53 months (IQR 33–74). The multivariate Cox regression analyses demonstrated that the only factor associated with BCR in very low-risk patients was increase in the pathologic Gleason score (GS) (HR: 2.185, p-value 0.048). In addition, multivariate logistic analyses identified prostate specific antigen (PSA) (OR: 1.353, p-value 0.010), PSA density (OR: 1.160, p-value 0.013), and suspicious lesion on mpMRI (OR: 1.995, p-value 0.019) as the independent preoperative predictors associated with the pathologic GS upgrade. In our study, the pathologic GS upgrade after radical prostatectomy in very low-risk prostate cancer patients demonstrated a negative impact on BCR and mpMRI is a good prognostic tool to predict the pathologic GS upgrade. We believe that the implementation of mpMRI would be beneficial to determine the treatment strategy for these patients. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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Open AccessArticle
Prevalence and Outcome of Secondary Hemophagocytic Lymphohistiocytosis Among SIRS Patients: Results from a Prospective Cohort Study
J. Clin. Med. 2019, 8(4), 541; https://doi.org/10.3390/jcm8040541
Received: 7 March 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 19 April 2019
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Abstract
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening condition clinically presenting as SIRS (Systemic Inflammatory Response Syndrome). However, there is no comprehensive data concerning diagnostic algorithms, prevalence, outcome and biomarker performance in SIRS patients. We conducted a prospective observational cohort study on 451 consecutive [...] Read more.
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening condition clinically presenting as SIRS (Systemic Inflammatory Response Syndrome). However, there is no comprehensive data concerning diagnostic algorithms, prevalence, outcome and biomarker performance in SIRS patients. We conducted a prospective observational cohort study on 451 consecutive patients fulfilling ≥2 SIRS criteria. The Hscore and the HLH-2004 criteria were used to determine the presence of sHLH, and the correlation of the screening-biomarkers ferritin, sCD25, and sCD163 with both scores was assessed. Out of 451 standard-care SIRS patients, five patients had high Hscores (≥169), suggesting incipient or HLH-like disease, and these patients were in urgent need for intensified therapy. However, none of these patients fulfilled five HLH-2004 criteria required for formal diagnosis. From the studied biomarkers, ferritin correlated strongest to both the HLH-2004 criteria and the Hscore (rs = 0.72, 0.41, respectively), and was the best predictor of 30-day survival (HR:1.012 per 100 μg/L, 95% CI: 1.004–1.021), when adjusted for patient’s age, sex, bacteremia and malignant underlying-disease. Also, the HLH-2004 (HR per point increase: 1.435, 95% CI: 1.1012–2.086) and the Hscore (HR per point increase:1.011, 95% CI: 1.002–1.020) were independent predictors of 30-day-survival. The Hscore detected patients in hyperinflammatory states requiring urgent therapy escalation. Degrees of hyperinflammation, as assessed by ferritin and both HLH scores, are associated with worse outcomes. Full article
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Open AccessArticle
Celiac Disease Prevalence Is Increased in Primary Sjögren’s Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study
J. Clin. Med. 2019, 8(4), 540; https://doi.org/10.3390/jcm8040540
Received: 29 March 2019 / Revised: 9 April 2019 / Accepted: 16 April 2019 / Published: 19 April 2019
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Abstract
Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and systemic [...] Read more.
Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc–CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis. Full article
(This article belongs to the Section Immunology)
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Open AccessArticle
Metastatic Tumors of the Sinonasal Cavity: A 15-Year Review of 17 Cases
J. Clin. Med. 2019, 8(4), 539; https://doi.org/10.3390/jcm8040539
Received: 1 March 2019 / Revised: 22 March 2019 / Accepted: 16 April 2019 / Published: 19 April 2019
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Abstract
Extranasal cancers that metastasize to the sinonasal cavity are very rare. To date, there are only limited reports regarding this rare condition within the literature. Therefore, we retrospectively reviewed all patients diagnosed with metastatic cancer of the sinonasal tract from 2003 to 2018 [...] Read more.
Extranasal cancers that metastasize to the sinonasal cavity are very rare. To date, there are only limited reports regarding this rare condition within the literature. Therefore, we retrospectively reviewed all patients diagnosed with metastatic cancer of the sinonasal tract from 2003 to 2018 at a tertiary academic medical center. Patient demographic data, clinical presentation, treatment modalities, and outcomes were investigated. There were a total of 17 patients (9 males and 8 females) included in the analysis. The mean age was 56.8 years (range 27–80). The most common primary malignancies were hepatocellular carcinoma (n = 3) and gastrointestinal tract adenocarcinoma (n = 3). The most common site of metastasis was the nasal cavity (n = 8). Five patients received radical tumor resection and the others underwent radiotherapy, chemotherapy, or combined chemoradiotherapy. The 2-year survival was 28%. In summary, metastasis to the sinonasal cavity remains extremely rare. A high degree of suspicion regarding the possibility of metastatic spread to the sinonasal region is necessary for patients with a previous history of malignancy who present with new sinonasal symptoms. The treatment strategy of sinonasal metastatic cancer is usually palliative therapy and the prognosis remains poor. However, early detection and diagnosis, coupled with aggressive treatment, may improve patient quality of life. Full article
(This article belongs to the Section Otolaryngology)
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Open AccessArticle
Predictors of Response to a Medial Branch Block: MRI Analysis of the Lumbar Spine
J. Clin. Med. 2019, 8(4), 538; https://doi.org/10.3390/jcm8040538
Received: 10 March 2019 / Revised: 16 April 2019 / Accepted: 17 April 2019 / Published: 19 April 2019
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Abstract
The aim of this study was to determine the association between radiologic spinal pathology and the response to medial branches block (MBB). This retrospective observational study compared 165 patients. A successful response was defined as ≥30% or a 2-point reduction in the numeric [...] Read more.
The aim of this study was to determine the association between radiologic spinal pathology and the response to medial branches block (MBB). This retrospective observational study compared 165 patients. A successful response was defined as ≥30% or a 2-point reduction in the numeric rating scale (NRS) compared with the baseline at the 1-month follow-up. The facet angle, facet angle difference, facet joint degeneration, disc height and spondylolisthesis grade were analyzed from an MRI at the L3 to S1 levels. Univariate and multivariate logistic regression analyses were used to evaluate independent factors associated with a successful response of MBB. In the univariate analysis, the disc height at L5–S1 and facet angle difference at L3–4 were lower in the positive responders (p = 0.022 and p = 0.087, respectively). In the multivariate analysis, the facet angle difference at L3–4 and disc height at L5–S1 were independent factors associated with a successful response (odds ratio = 0.948; p = 0.038 and odds ratio = 0.864; p = 0.038, respectively). In patients with a degenerative disc at L5–S1, MBB can lead to a good response for at least one month. In patients with facet tropism at L3–4 level, the response to MBB after one month is likely to be poor. Full article
(This article belongs to the Section Anesthesiology)
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Open AccessArticle
T-Regulatory Cells Confer Increased Myelination and Stem Cell Activity after Stroke-Induced White Matter Injury
J. Clin. Med. 2019, 8(4), 537; https://doi.org/10.3390/jcm8040537
Received: 13 March 2019 / Revised: 5 April 2019 / Accepted: 17 April 2019 / Published: 19 April 2019
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Abstract
Stroke-induced hypoxia causes oligodendrocyte death due to inflammation, lack of oxygen and exacerbation of cell death. Bone marrow-derived stem cells (BMSCs) possess an endogenous population of T-regulatory cells (Tregs) which reduce secretion of pro-inflammatory cytokines that lead to secondary cell death. [...] Read more.
Stroke-induced hypoxia causes oligodendrocyte death due to inflammation, lack of oxygen and exacerbation of cell death. Bone marrow-derived stem cells (BMSCs) possess an endogenous population of T-regulatory cells (Tregs) which reduce secretion of pro-inflammatory cytokines that lead to secondary cell death. Here, we hypothesize that oligodendrocyte progenitor cells (OPCs) cultured with BMSCs containing their native Treg population show greater cell viability, less pro-inflammatory cytokine secretion and greater myelin production after exposure to oxygen-glucose deprivation and reoxygenation (OGD/R) than OPCs cultured without Tregs. OPCs were cultured and then exposed to OGD/R. BMSCs with or without Tregs were added to the co-culture immediately after ischemia. The Tregs were depleted by running the BMSCs through a column containing a magnetic substrate. Fibroblast growth factor beta (FGF-β) and interleukin 6 (IL-6) ELISAs determined BMSC activity levels. Immunohistochemistry assessed OPC differentiation. OPCs cultured with BMSCs containing their endogenous Tregs showed increased myelin production compared to the BMSCs with depleted Tregs. IL-6 and FGF-β were increased in the group cultured with Tregs. Collectively, these results suggest that BMSCs containing Tregs are more therapeutically active, and that Tregs have beneficial effects on OPCs subjected to ischemia. Tregs play an important role in stem cell therapy and can potentially treat white matter injury post-stroke. Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cells in Immunity and Disease)
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Open AccessReview
Short-Term Effects of Anodal Transcranial Direct Current Stimulation on Endurance and Maximal Force Production: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(4), 536; https://doi.org/10.3390/jcm8040536
Received: 22 March 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 18 April 2019
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Abstract
The purpose of the present systematic review and meta-analysis was to explore the effects of transcranial direct current stimulation (tDCS) on endurance (i.e., time to task failure (TTF)) and maximal voluntary contraction (MVC). Furthermore, we aimed to analyze whether the duration of stimulation, [...] Read more.
The purpose of the present systematic review and meta-analysis was to explore the effects of transcranial direct current stimulation (tDCS) on endurance (i.e., time to task failure (TTF)) and maximal voluntary contraction (MVC). Furthermore, we aimed to analyze whether the duration of stimulation, the brain region targeted for stimulation, and the task performed could also influence motor performance. We performed a systematic literature review in the databases MEDLINE and Web of Science. The short-term effects of anodal tDCS and sham stimulation (placebo) were considered as experimental and control conditions, respectively. A total of 31 interventions were included (MVC = 13; TTF = 18). Analysis of the strength-related tDCS studies showed small improvements in the MVC (SMD = 0.19; 95% CI = −0.02, 0.41; p = 0.08). However, the results of the endurance-related interventions indicated a moderate effect on TTF performance (SMD = 0.26; 95% CI = 0.07, 0.45; p = 0.008). Furthermore, the sub-analysis showed that anodal tDCS over M1 and stimulation durations longer than 10 min produced the best results in terms of TTF performance enhancement. Additionally, the effects of anodal tDCS were larger during full body exercises (i.e., cycling) when compared to uniarticular tasks. In conclusion, the current meta-analysis indicated that anodal tDCS leads to small and moderate effects on MVC and TTF, respectively. Full article
(This article belongs to the Section Neuroscience)
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