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Medicina, Volume 55, Issue 2 (February 2019)

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Cover Story (view full-size image) Oral mucositis is a side effect of chemotherapy or/and radiotherapy, affecting about 20–80% of [...] Read more.
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Open AccessArticle
Physical Fitness and Body Composition in Women with Systemic Lupus Erythematosus
Received: 29 November 2018 / Revised: 13 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
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Abstract
Background and objectives: Higher physical fitness is associated with a more favorable weight and body composition in the general population, although this association has not been studied in patients with systemic lupus erythematosus (SLE). The aim of the present study was to examine [...] Read more.
Background and objectives: Higher physical fitness is associated with a more favorable weight and body composition in the general population, although this association has not been studied in patients with systemic lupus erythematosus (SLE). The aim of the present study was to examine the association of different components of physical fitness with body composition in women with SLE with mild disease activity. Materials and Methods: This cross-sectional study included 77 women with SLE (43.2 ± 13.8 years old) and clinical stability during the previous 6 months. Body composition (including body mass index (BMI), fat mass index (FMI), waist circumference, waist-to-height ratio and waist-to-hip ratio) was assessed using a stadiometer, an anthropometric tape, and a bioimpedance device. Physical fitness included cardiorespiratory fitness (Siconolfi step test and 6 min walk test), muscular strength (handgrip strength test as upper body measure and 30 s chair stand as lower body measure), and flexibility (back-scratch test). Participants with a fitness level equal or above the median of the study sample were categorized as “fit” and those below the median were categorized as “unfit”. Linear regression assessed the association of physical fitness with body composition parameters. Results: Cardiorespiratory fitness and upper body muscular strength were negatively associated with BMI, FMI, waist circumference, and waist-to-height ratio (all, p < 0.05). Lower body muscular strength and flexibility were negatively related to FMI, waist circumference, waist-to-height ratio, and waist-to-hip ratio (all, p < 0.05). These relationships were still significant after controlling for age, disease duration, accrual damage, and SLE activity. Overall, fit patients presented significantly lower values in all body composition parameters compared to unfit patients (all, p < 0.05). Conclusions: The main findings of the present study suggest that physical fitness is inversely associated with body composition in women with SLE. Given the cross-sectional nature of this study, future clinical trials should study the causal pathways underlying these relationships. Full article
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Open AccessReview
Recently Discovered Interstitial Cell Population of Telocytes: Distinguishing Facts from Fiction Regarding Their Role in the Pathogenesis of Diverse Diseases Called “Telocytopathies”
Received: 4 December 2018 / Revised: 14 January 2019 / Accepted: 11 February 2019 / Published: 18 February 2019
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Abstract
In recent years, the interstitial cells telocytes, formerly known as interstitial Cajal-like cells, have been described in almost all organs of the human body. Although telocytes were previously thought to be localized predominantly in the organs of the digestive system, as of 2018 [...] Read more.
In recent years, the interstitial cells telocytes, formerly known as interstitial Cajal-like cells, have been described in almost all organs of the human body. Although telocytes were previously thought to be localized predominantly in the organs of the digestive system, as of 2018 they have also been described in the lymphoid tissue, skin, respiratory system, urinary system, meninges and the organs of the male and female genital tracts. Since the time of eminent German pathologist Rudolf Virchow, we have known that many pathological processes originate directly from cellular changes. Even though telocytes are not widely accepted by all scientists as an individual and morphologically and functionally distinct cell population, several articles regarding telocytes have already been published in such prestigious journals as Nature and Annals of the New York Academy of Sciences. The telocyte diversity extends beyond their morphology and functions, as they have a potential role in the etiopathogenesis of different diseases. The most commonly described telocyte-associated diseases (which may be best termed “telocytopathies” in the future) are summarized in this critical review. It is difficult to imagine that a single cell population could be involved in the pathogenesis of such a wide spectrum of pathological conditions as extragastrointestinal stromal tumors (“telocytomas”), liver fibrosis, preeclampsia during pregnancy, tubal infertility, heart failure and psoriasis. In any case, future functional studies of telocytes in vivo will help to understand the mechanism by which telocytes contribute to tissue homeostasis in health and disease. Full article
Open AccessReview
Use of Magnetic Resonance Imaging in Evaluating Fetal Brain and Abdomen Malformations during Pregnancy
Received: 15 November 2018 / Revised: 6 January 2019 / Accepted: 11 February 2019 / Published: 17 February 2019
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Abstract
Magnetic resonance imaging (MRI) is used as a clarifying technique after a high-resolution ultrasound examination during pregnancy. Combining ultrasound with MRI, additional diagnostic information is obtained or ultrasound diagnosis is frequently corrected. High spatial resolution provides accurate radiological imaging of internal organs and [...] Read more.
Magnetic resonance imaging (MRI) is used as a clarifying technique after a high-resolution ultrasound examination during pregnancy. Combining ultrasound with MRI, additional diagnostic information is obtained or ultrasound diagnosis is frequently corrected. High spatial resolution provides accurate radiological imaging of internal organs and widens possibilities for detecting perinatal development disorders. The safety of MRI and the use of intravenous contrast agent gadolinium are discussed in this article. There is no currently available evidence that MRI is harmful to the fetus, although not enough research has been carried out to prove enduring safety. MRI should be performed when the benefit outweighs the potential side effects. The narrative review includes several clinical cases of fetal MRI performed in Vilnius University Hospital Santaros Clinics. Full article
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Open AccessArticle
Activation of TF-Dependent Blood Coagulation Pathway and VEGF-A in Patients with Essential Thrombocythemia
Received: 25 November 2018 / Revised: 11 February 2019 / Accepted: 11 February 2019 / Published: 16 February 2019
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Abstract
Background and objectives: Recent studies suggest that a vascular endothelial growth factor (VEGF-A) may be involved in the thrombotic process by stimulating the expression of tissue factor in vascular endothelial cells. Tissue factor (TF) can also stimulate the transcription of the gene encoding [...] Read more.
Background and objectives: Recent studies suggest that a vascular endothelial growth factor (VEGF-A) may be involved in the thrombotic process by stimulating the expression of tissue factor in vascular endothelial cells. Tissue factor (TF) can also stimulate the transcription of the gene encoding VEGF-A. The relationship between coagulation and angiogenesis in myeloproliferative neoplasms is not fully understood. The aim of this study was to evaluate the concentration of TF in relation to VEGF-A in the blood of patients with essential thrombocythemia (ET). Patients and methods: The study group consisted of 130, newly diagnosed patients with ET (mean age 61 years). The control group consisted of 35 healthy volunteers (mean age 51 years). Concentrations of VEGF-A, TF, and tissue factor pathway inhibitor (TFPI) were analysed using immunoenzymatic methods. TF and TFPI activities were performed using chromogenic assays. Results: The median concentration of TF Ag was 3-fold higher and the TF activity was more than 15-fold higher in ET patients than in normal individuals. There were no statistically significant differences in the TFPI concentration and activity between groups. VEGF-A was significantly increased in patients with ET (p < 0.000001). Analysis of correlations revealed a positive correlation between VEGF-A and TF Ag as well as a positive correlation between VEGF-A and TFPI activity. Conclusions: The simultaneous increase of TF concentration and activity, VEGF-A in the blood of patients with ET, as well as a positive correlation between the concentration of TF and VEGF-A demonstrates the coexistence of TF-dependent coagulation and activation of angiogenesis. Full article
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Open AccessArticle
Relationships between Quadriceps Tendon Elasticity and Knee Flexion Angle in Young Healthy Adults
Received: 28 December 2018 / Revised: 8 February 2019 / Accepted: 11 February 2019 / Published: 15 February 2019
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Abstract
Background and objectives: Although tendon elasticity by elastography is useful for diagnosing tendon disorders and planning rehabilitation regimens of the tendon, there are few reports on the quadriceps tendon. Moreover, relationships between the quadriceps tendon elasticity and knee angle have not been investigated. [...] Read more.
Background and objectives: Although tendon elasticity by elastography is useful for diagnosing tendon disorders and planning rehabilitation regimens of the tendon, there are few reports on the quadriceps tendon. Moreover, relationships between the quadriceps tendon elasticity and knee angle have not been investigated. The purpose of this study was to clarify the relationship between quadriceps tendon elasticity and knee flexion angle in young healthy adults using elastography, and to investigate the difference in elasticity by sex and leg dominance. Materials and Methods: A total of 40 knees in 20 young healthy adults were included in this study (age: 25.5 (23.3–27.5) years). At knee flexion of 30°, 60°, and 90°, quadriceps tendon elasticity was measured using ShearWave™ Elastography during the ultrasound examination. Results: There were significant differences in the elasticity between all angles (p < 0.001). Elasticity was increased more at 60° than at 30° and at 90° than at 60°. Elasticity in men was higher than that in women at 60° (p = 0.029). There were no differences (p = 0.798) in elasticity at each angle between the dominant and non-dominant legs. Conclusions: The quadriceps tendon elasticity increased according to the knee flexion angle in young healthy adults. Moreover, elasticity was affected by sex, but not by leg dominance. Clinically, in a rehabilitation regimen, attention should be paid to exercises that could increase stiffness accompanying flexion of the knee to avoid further tendon damage as risk management in the acute phase. Full article
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Open AccessArticle
Is Capacity Building Training Effective for Changing Attitudes toward Health Inequalities? Experience from a Norway Grants Project in Lithuania
Received: 10 August 2018 / Revised: 28 January 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
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Abstract
Background and Objectives: In 2014–2017, the Lithuanian University of Health Sciences and partners implemented the project, ‘Development of the Model for the Strengthening of the Capacities to Identify and Reduce Health Inequalities’, which was financed by The Norwegian Financial Mechanism 2009–2014 Public [...] Read more.
Background and Objectives: In 2014–2017, the Lithuanian University of Health Sciences and partners implemented the project, ‘Development of the Model for the Strengthening of the Capacities to Identify and Reduce Health Inequalities’, which was financed by The Norwegian Financial Mechanism 2009–2014 Public Health Initiatives Program. One of objectives of this project was to increase the awareness about public health and related specialist knowledge and skills in the field of health inequalities. This paper evaluates the effectiveness of capacity-training sessions on capacity building regarding increasing the awareness and knowledge that is needed for addressing health inequalities. Materials and Methods: Participants attending capacity-building seminars were asked to complete the same questionnaires before and after these training sessions. A total of 145 questionnaires were received (response rate 71.8%). The evaluation of changes in the pre-survey and post-survey responses in relation to a nonparametric analysis of two related samples was performed using the Wilcoxon test. Results: Respondents were asked to identify the general importance of health inequalities to the national public health agenda. The pre-training median of the survey was nine (minimum four; maximum 10), and post-training was 10 [minimum five; maximum 10] (p < 0.001). Unemployed, low-paid, and low-educated people were identified as the most vulnerable groups of society in terms of health inequalities. A more effective tobacco and alcohol control was identified as the most important inequality measure needed. An absolute majority of participants emphasized the need for intersectoral collaboration for the effective reduction of health inequalities. Conclusion: The findings from our study suggest that capacity-building sessions can be effective measures for increasing awareness of health inequalities. It is expected that the outcomes of these training opportunities will act as facilitators for further engagement and ongoing approaches to addressing health inequalities. Full article
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Open AccessArticle
Comparison of 30-Day MACE between Immediate versus Staged Complete Revascularization in Acute Myocardial Infarction with Multivessel Disease, and the Effect of Coronary Lesion Complexity
Received: 6 January 2019 / Revised: 8 February 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
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Abstract
Background and objective: In patients with acute myocardial infarction and multivessel disease, the timing of intervention to non-culprit lesions is still a matter of debate, especially in patients without shock. This study aimed to compare the effect of multivessel intervention, performed at index [...] Read more.
Background and objective: In patients with acute myocardial infarction and multivessel disease, the timing of intervention to non-culprit lesions is still a matter of debate, especially in patients without shock. This study aimed to compare the effect of multivessel intervention, performed at index percutaneous coronary intervention (PCI) (MVI-I) or index hospitalization (MVI-S), on the 30-day results of acute myocardial infarction (AMI), and to investigate the effect of coronary lesion complexity assessed by the Syntax (Sx) score on the timing of multivessel intervention. Materials and methods: We enrolled 180 patients with MVI-I, and 425 patients with MVI-S. The major adverse cardiovascular events (MACE) for this study were identified as mortality, nonfatal myocardial infarction, nonfatal stroke, acute heart failure, ischemia driven revascularization, major bleeding, and acute renal failure developed within 30 days. Results: The unadjusted MACE rates at 30 days were 11.2% and 5% among those who underwent MVI-I and MVI-S, respectively (OR 3.02; 95% confidence interval (CI) 1.51–6.02; p = 0.002). Associations were statistically significant after adjusting for covariates in the penalized multivariable model (adjusted OR 2.06; 95%CI 1.02–4.18; p = 0.043), propensity score adjusted multivariable model (adjusted OR 2.46; 95%CI 1.19–5.07; p = 0.015), and IPW (adjusted OR 2.11; 95%CI 1.28–3.47; p = 0.041). We found that the Syntax score of lesions did not affect the results. Conclusion: MVI-S was associated with a lower incidence of major adverse cardiovascular events within 30 days after discharge. Full article
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Open AccessReview
IL33/ST2 Axis in Diabetic Kidney Disease: A Literature Review
Received: 10 December 2018 / Revised: 11 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
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Abstract
Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is [...] Read more.
Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is a receptor for IL-33, expressed selectively on a subset of Th2 cells, mediating some of their functions. The IL-33/ST2 axis plays an important role in several acute and chronic inflammatory diseases, including asthma and rheumatoid arthritis. Different disorders are related to the activity of IL-33, ST2, or their axis, including cardiovascular disease or renal disturbances. Therefore, in the present work, a literature review was conducted, covering the period from 1 January 2000 to 30 November 2018, in PubMed, ScienceDirect, and Google Scholar database, to assess the involvement of the IL-33/ST2 axis in diabetic kidney disease. 6 articles directly dealing with the argument were identified, highlighting a clear link between IL-33/ST2 axis and diabetic kidney disease or related nephropathy. Overall, the involvement of ST2 seems to be more predictive than IL-33, especially in investigating the deterioration of kidney function; however, both compounds are pivotal in the field of renal diseases. Future studies are required to confirm the scientific evidences on larger and more heterogeneous cohorts. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
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Open AccessArticle
Ventilator-Associated Pneumonia due to Drug-Resistant Acinetobacter baumannii: Risk Factors and Mortality Relation with Resistance Profiles, and Independent Predictors of In-Hospital Mortality
Received: 15 December 2018 / Revised: 21 January 2019 / Accepted: 7 February 2019 / Published: 13 February 2019
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Abstract
Background and objectives: High mortality and healthcare costs area associated with ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (A. baumannii). The data concerning the link between multidrug-resistance of A. baumannii strains and outcomes remains controversial. Therefore, we aimed to identify the [...] Read more.
Background and objectives: High mortality and healthcare costs area associated with ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (A. baumannii). The data concerning the link between multidrug-resistance of A. baumannii strains and outcomes remains controversial. Therefore, we aimed to identify the relation of risk factors for ventilator-associated pneumonia (VAP) and mortality with the drug resistance profiles of Acinetobacter baumannii (A. baumannii) and independent predictors of in-hospital mortality. Methods: A retrospective ongoing cohort study of 60 patients that were treated for VAP due to drug-resistant A. baumannii in medical-surgical intensive care units (ICU) over a two-year period was conducted. Results: The proportions of multidrug-resistant (MDR), extensively drug-resistant (XDR), and potentially pandrug-resistant (pPDR) A. baumannii were 13.3%, 68.3%, and 18.3%, respectively. The SAPS II scores on ICU admission were 42.6, 48.7, and 49 (p = 0.048); hospital length of stay (LOS) prior to ICU was 0, one, and two days (p = 0.036), prior to mechanical ventilation (MV)—0, 0, and three days (p = 0.013), and carbapenem use prior to VAP—50%, 29.3%, and 18.2% (p = 0.036), respectively. The overall in-hospital mortality rate was 63.3%. In MDR, XDR, and pPDR A. baumannii VAP groups, it was 62.5%, 61.3%, and 72.7% (p = 0.772), respectively. Binary logistic regression analysis showed that female gender (95% OR 5.26; CI: 1.21–22.83), SOFA score on ICU admission (95% OR 1.28; CI: 1.06–1.53), and RBC transfusion (95% OR 5.98; CI: 1.41–25.27) were all independent predictors of in-hospital mortality. Conclusions: The VAP risk factors: higher SAPS II score, increased hospital LOS prior to ICU, and MV were related to the higher resistance profile of A. baumannii. Carbapenem use was found to be associated with the risk of MDR A. baumannii VAP. Mortality due to drug-resistant A. baumannii VAP was high, but it was not associated with the A. baumannii resistance profile. Female gender, SOFA score, and RBC transfusion were found to be independent predictors of in-hospital mortality. Full article
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Open AccessArticle
Racial and Income Disparities in Health-Related Quality of Life among Smokers with a Quit Attempt in Louisiana
Received: 2 November 2018 / Revised: 27 January 2019 / Accepted: 10 February 2019 / Published: 13 February 2019
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Abstract
Background and objectives: Smoking is associated with a lower health-related quality of life (HRQOL). However, there is little information about the association between HRQOL in relation to race, income, and smoking status. The present study aimed to assess the association between HRQOL and [...] Read more.
Background and objectives: Smoking is associated with a lower health-related quality of life (HRQOL). However, there is little information about the association between HRQOL in relation to race, income, and smoking status. The present study aimed to assess the association between HRQOL and smoking status for those of different races and income levels. Materials and Methods: This study applied a cross-sectional design using data from the 2017 patient survey of the Louisiana Tobacco Control Initiative. We obtained 1108 responses from patients at eight Louisiana public hospitals. The EuroQol (EQ-5D) US index score assessed HRQOL. Smoking status was classified into four groups: never smoked, former smoker, current smoker with a quit attempt, and current smoker without a quit attempt. Multivariate linear regression analyses were used to estimate the HRQOL for black or African Americans and whites. Results: The patients were predominantly black or African American (58.9%) with lower-income (71.2%). Bivariate analyses showed that there were differences in income levels between black or African Americans and whites (p = 0.006). Moreover, black or African Americans (median = 0.80) had a higher mean of HRQOL than whites (median = 0.76). Among lower-income black or African Americans, current smokers with a quit attempt had a lower HRQOL than current smokers (coefficient = −0.12; p < 0.01). Conclusions: Racial and income disparities were evident with regards to HRQOL, with lower-income black or African Americans who were current smokers with a quit attempt having a lower HRQOL. Intervention programs for smoking cessation should target lower-income black or African American smokers who have a prior quit attempt and provide effective cessation services to help them quit smoking and improve their HRQOL. Full article
Open AccessArticle
Common Variations in Prothrombotic Genes and Susceptibility to Ischemic Stroke in Young Patients: A Case-Control Study in Southeast Iran
Received: 28 October 2018 / Revised: 4 February 2019 / Accepted: 4 February 2019 / Published: 13 February 2019
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Abstract
Background and Objective: Evidence indicates that genetic factors may be involved in the risk of ischemic stroke (IS). The aim of this study was to assess the effect of genetic polymorphisms located in exons or untranslated regions of MTHFR as well as FV [...] Read more.
Background and Objective: Evidence indicates that genetic factors may be involved in the risk of ischemic stroke (IS). The aim of this study was to assess the effect of genetic polymorphisms located in exons or untranslated regions of MTHFR as well as FV genes on ischemic stroke. Materials and Methods: In this case-control study, 106 patients with IS and 157 healthy volunteers (age <50 years) were genotyped for MTHFR C677T, A1298C, C2572A and C4869G, FVL, and prothrombin G20210A polymorphisms. Results: The MTHFR 677CT genotype was more frequent in patients and increased risk of IS with Odds Ratio = 1.9. The MTHFR A1298C and C2572A polymorphisms were not associated with IS in dominant and recessive models. Our findings showed a significant decrease in the MTHFR 4869CG genotype in IS patients, and this variant was associated with a decreased risk of IS in the dominant model. The CAAT haplotype was associated with increased risk, and the GAAC haplotype was associated with decreased risk of IS compared to other haplotypes. There was no relation between FVL G1691A polymorphism and IS risk. Conclusions: The present study showed that the MTHFR 677CT genotype was more frequent and the MTHFR 4869CG genotype was less frequent in young IS patients. Full article
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Open AccessArticle
Use of Complementary and Alternative Medicine by Patients with Irritable Bowel Syndrome According to the Roma IV Criteria: A Single-Center Italian Survey
Received: 19 December 2018 / Revised: 25 January 2019 / Accepted: 8 February 2019 / Published: 13 February 2019
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Abstract
Aim: This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. Methods: Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. [...] Read more.
Aim: This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. Methods: Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. Demographic features and characteristics potentially associated with the use of CAM were collected. A validated, self-administered, survey questionnaire dealing with CAM and patients’ level of knowledge, motivation, perception, and information seeking-behavior toward the use of CAM was analyzed. Multivariate logistic regression analysis was performed in order to identify predictors of CAM use among participants. Results: Among 156 patients claiming IBS, 137 (88%) met the Rome IV criteria, and 62 of them (45%) were CAM users. Biologically based therapy was the most chosen CAM (78%). Significant risk factors (adjusted odds ratio, 95% confidence interval) for the use of CAM were female gender (7.22, 2.31–22.51), a higher BMI (1.16, 1.02–1.33), and a good knowledge of CAM (4.46, 1.73–11.45), while having children was a protective factor (0.25, 0.07–0.95). Only 19% of patients used CAM due to medical advice and over half (51%) thought it was a “more natural” approach. Although a minority of patients (16%) had full satisfaction from CAM, 81% of users would repeat the CAM experience for their IBS symptoms. Conclusions: The widespread use of CAM in IBS, the patients’ belief in its safety, and their willingness to re-use it suggest that knowledge of health-care providers and patient education should be improved. Full article
(This article belongs to the Special Issue Complementary and Integrative Medicine)
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Open AccessArticle
Lung Ultrasound B-lines Occurrence in Relation to Left Ventricular Function and Hydration Status in Hemodialysis Patients
Received: 9 January 2019 / Revised: 6 February 2019 / Accepted: 7 February 2019 / Published: 12 February 2019
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Abstract
Background and objective: Reliable assessment of the fluid status in hemodialysis (HD) patients is often difficult. A lung ultrasound with an assessment of the B-lines (“lung comets” (LCs)) number is a novel hydration status measure. However, the occurrence of left ventricular dysfunction may [...] Read more.
Background and objective: Reliable assessment of the fluid status in hemodialysis (HD) patients is often difficult. A lung ultrasound with an assessment of the B-lines (“lung comets” (LCs)) number is a novel hydration status measure. However, the occurrence of left ventricular dysfunction may have a significant effect on pulmonary congestion and further modulate the LC number. The aim of this study was to analyze to what extent left ventricular dysfunction, pulmonary hypertension, and hypervolemia affect the occurrence of LC in a cohort of prevalent HD patients. Material and methods: This cross-sectional study included 108 assessments performed in 54 patients who attended thrice weekly outpatient HD. Each patient’s fluid status was evaluated twice, prior to HD sessions, using echocardiography, LC number assessment, measurement of inferior vena cava (IVC) diameters, and bioelectric impedance analysis (BIA). Patients were stratified into three subgroups according to their LC number. Results: There were 76 separate assessments with mild (<14), 16 with moderate (14–30), and 16 with severe (>30) LC occurrence. There was a negative correlation between the LC number and left ventricular ejection fraction (LVEF), and positive correlations between the LC number and mitral gradient, and the left and right atrium area and volume, but not with the BIA-derived relative fluid overload. Multivariate linear regression analysis revealed that the LC number was proportionally related to the mitral gradient (β = 0.407 (0.247–0.567), p < 0.001) and IVC max diameter (β = 0.219 (0.060–0.378), p < 0.01), and was inversely related to LVEF (β = −0.431 (−0.580 to −0.282), p < 0.001). Conclusions: The number of LCs appears to reflect both overhydration and left ventricular dysfunction in our HD patients cohort. Therefore, heart failure must be considered as an important factor limiting the usefulness of LCs number assessment in this population. Full article
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Open AccessArticle
Antibiotic Prescribing Practices and Errors among Hospitalized Pediatric Patients Suffering from Acute Respiratory Tract Infections: A Multicenter, Cross-Sectional Study in Pakistan
Received: 5 October 2018 / Revised: 29 January 2019 / Accepted: 5 February 2019 / Published: 11 February 2019
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Abstract
Background and objective: The noncompliance of treatment guidelines by healthcare professionals, along with physiological variations, makes the pediatric population more prone to antibiotic prescribing errors. The present study aims to evaluate the prescribing practices and errors of the most frequently prescribed antibiotics among [...] Read more.
Background and objective: The noncompliance of treatment guidelines by healthcare professionals, along with physiological variations, makes the pediatric population more prone to antibiotic prescribing errors. The present study aims to evaluate the prescribing practices and errors of the most frequently prescribed antibiotics among pediatric patients suffering from acute respiratory tract infections who had different lengths of stay (LOS) in public hospitals. Methods: A retrospective, cross-sectional study was conducted in five tertiary-care public hospitals of Lahore, Pakistan, between 1 January 2017 and 30 June 2017. The study population consisted of pediatric inpatients aged 0 to 9 years. Results: Among the 11,892 pediatric inpatients, 82.8% were suffering from lower acute respiratory tract infections and had long LOS (53.1%) in hospital. Penicillins (52.4%), cephalosporins (16.8%), and macrolides (8.9%) were the most frequently prescribed antibiotics. Overall, 40.8% of the cases had antibiotic prescribing errors related to wrong dose (19.9%), wrong frequency (18.9%), and duplicate therapy (18.1%). Most of these errors were found in the records of patients who had long LOS in hospital (53.1%). Logistic regression analysis revealed that the odds of prescribing errors were lower in female patients (OR = 0.6, 95% CI = 0.1–0.9, p-value = 0.012). Patients who were prescribed with ≥3 antibiotics per prescription (OR = 1.724, 95% CI = 1.1–2.1, p-value = 0.020), had long LOS (OR = 12.5, 95% CI = 10.1–17.6, p-value < 0.001), and were suffering from upper respiratory tract infections (URTI) (OR = 2.8, 95% CI = 1.7–3.9, p-value < 0.001) were more likely to experience prescribing errors. Conclusion: Antibiotics were commonly prescribed to patients who had long LOS. Prescribing errors (wrong dose, wrong frequency, and duplicate therapy) were commonly found in cases of lower respiratory tract infections (LRTIs), especially among those who had prolonged stay in hospital. Full article
Open AccessFeature PaperArticle
The Effects of High-Intensity Interval Exercise and Hypoxia on Cognition in Sedentary Young Adults
Received: 4 January 2019 / Revised: 7 February 2019 / Accepted: 8 February 2019 / Published: 10 February 2019
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Abstract
Background and Objectives: Limited research has evaluated the effects of acute exercise on cognition under different conditions of inspired oxygenation. Thus, the purpose of this study was to examine the effects of high-intensity interval exercise (HIE) under normoxia (inspired fraction of oxygen (FIO [...] Read more.
Background and Objectives: Limited research has evaluated the effects of acute exercise on cognition under different conditions of inspired oxygenation. Thus, the purpose of this study was to examine the effects of high-intensity interval exercise (HIE) under normoxia (inspired fraction of oxygen (FIO2): 0.209) and moderate hypoxia (FIO2: 0.154) on cognitive function. Design: A single-blinded cross-over design was used to observe the main effects of exercise and oxygen level, and interaction effects on cognitive task performance. Methods: Twenty inactive adults (10 males and 10 females, 19–27 years old) performed a cognitive task (i.e., the Go/No-Go task) before and immediately after an acute bout of HIE under normoxic and hypoxic conditions. The HIE comprised 10 repetitions of 6 s high-intensity cycling against 7.5% body weight interspersed with 30 s passive recovery. Heart rate, peripheral oxygen saturation (SpO2) and rating of perceived exertion were monitored. Results: The acute bout of HIE did not affect the reaction time (p = 0.204, η2 = 0.083) but the accuracy rate decreased significantly after HIE under both normoxic and hypoxic conditions (p = 0.001, η2 = 0.467). Moreover, moderate hypoxia had no influence either on reaction time (p = 0.782, η2 = 0.004) or response accuracy (p = 0.972, η2 < 0.001). Conclusions: These results indicate that an acute session of HIE may impair response accuracy immediately post-HIE, without sacrificing reaction time. Meanwhile moderate hypoxia was found to have no adverse effect on cognitive function in inactive young adults, at least in the present study. Full article
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Open AccessReview
Targeted Therapies in Cholangiocarcinoma: Emerging Evidence from Clinical Trials
Received: 15 December 2018 / Revised: 28 January 2019 / Accepted: 1 February 2019 / Published: 8 February 2019
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Abstract
Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs [...] Read more.
Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs and symptoms in the early stages. This fact, along with the poor results of the local and systemic therapies currently employed, is responsible for the poor outcome of CCA patients and strongly supports the need for novel therapeutic agents and strategies. In recent years, the introduction of next-generation sequencing technologies has opened new horizons for a better understanding of the genetic pathophysiology of CCA and, consequently, for the identification and evaluation of new treatments tailored to the molecular features or alterations progressively elucidated. In this review article, we describe the potential targets under investigation and the current molecular therapies employed in biliary tract cancers. In addition, we summarize the main drugs against CCA under evaluation in ongoing trials and describe the preliminary data coming from these pioneering studies. Full article
(This article belongs to the Special Issue Liver Cancer: Molecular Mechanisms and Targeted Therapies)
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Open AccessArticle
Correlation of Thyroid Transcription Factor-1 Expression with EGFR Mutations in Non-Small-Cell Lung Cancer: A Meta-Analysis
Received: 30 January 2019 / Accepted: 4 February 2019 / Published: 7 February 2019
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Abstract
Objectives: This meta-analysis investigated the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) to clarify whether TTF-1 can be a potential surrogate marker for EGFR mutation status in advanced NSLCL. [...] Read more.
Objectives: This meta-analysis investigated the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) to clarify whether TTF-1 can be a potential surrogate marker for EGFR mutation status in advanced NSLCL. Methods: A systematic searching of databases, including PubMed, EMBASE, Cochrane Library, and Google Scholar, was performed to identify studies assessing the correlation of TTF-1 expression with EGFR mutations. From 17 studies, 9764 patients were included in the combined analysis of odds ratio (OR) for the correlation between TTF-1 expression and EGFR mutations. Results: Compared with NSCLCs showing negative TTF-1 expression, tumors harboring TTF-1 overexpression showed a significantly higher rate of EGFR mutations (OR = 5.19, 95% confidence interval: 3.60–7.47, p < 0.00001). This correlation was observed in both subgroups of East Asian (OR = 4.33, 95% CI: 3.46–5.41, p < 0.00001) and European patients (OR = 4.64, 95% CI: 1.41–15.28, p < 0.01). In addition, TTF-1 expression was significantly associated with EGFR mutations in exon 19 (OR = 4.63, 95% CI: 2.89–7.41, p < 0.00001) as well as exon 21 (OR = 3.16, 95% CI: 1.04–9.60, p = 0.04). Conclusions: This meta-analysis demonstrates a significant correlation between TTF-1 expression and EGFR mutations in patients with NSCLC. The status of TTF-1 expression may be a biomarker to guide anticancer treatment in patients with NSCLC and unknown EGFR mutation status. Full article
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Open AccessCommunication
Common Polymorphisms Linked to Obesity and Cardiovascular Disease in Europeans and Asians are Associated with Type 2 Diabetes in Mexican Mestizos
Received: 31 December 2018 / Revised: 3 February 2019 / Accepted: 5 February 2019 / Published: 5 February 2019
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Abstract
Background and objectives: Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos. Materials and Methods [...] Read more.
Background and objectives: Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos. Materials and Methods: A total of 1358 subjects from 30 to 85 years old were genotyped for five loci: CXCL12 rs501120; CDNK2A/B rs1333049; HNF-1α rs2259816; FTO rs9939609; and LEP rs7799039. We used logistic regressions to test the effect of each locus on T2D in two case–control groups with obesity and without obesity. Also, linear regression models on glucose and glycated hemoglobin (HbA1c) were carried out on the whole sample, adjusted by age, gender, and body mass index. Results: The CXCL12 rs501120 C allele (OR = 1.96, p = 0.02), the FTO rs9939609 A allele (OR = 2.20, p = 0.04) and the LEP rs7799039 A allele (OR = 0.6, p = 0.03) were significantly associated with T2D in obesity case–control group. No significant association was found in the non-obesity case–control group. The linear regression model showed that CDNK2A/B rs1333049 C allele (β = 0.4, p = 0.03) and FTO rs9939609 A allele (β = 0.5, p = 0.03), were significantly associated with HbA1c, but no association was found among the loci with the glucose levels. Conclusions: Polymorphisms previously linked with obesity and cardiovascular events were also associated with T2D and high levels of HbA1c. Furthermore, we must point at the fact that this is the first report where polymorphisms CXCL12 rs501120 and LEP rs7799039 are associated with T2D in subjects with obesity. Full article
(This article belongs to the Special Issue Type 2 Diabetes and Insulin Resistance)
Open AccessArticle
Guidelines-Driven Educational Intervention Promotes Healthy Lifestyle Among Adolescents and Adults: A Serbian National Longitudinal Study
Received: 11 January 2019 / Revised: 29 January 2019 / Accepted: 29 January 2019 / Published: 4 February 2019
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Abstract
Background and objectives: The effectiveness of short-term focused educational programs to change health behaviors across large populations seems to be poorly described so far. The main aim of the present study was to evaluate an age-specific 45-min educational program, designed in accordance with [...] Read more.
Background and objectives: The effectiveness of short-term focused educational programs to change health behaviors across large populations seems to be poorly described so far. The main aim of the present study was to evaluate an age-specific 45-min educational program, designed in accordance with the current U.S. Department of Health and Human Services and U.S. Department of Agriculture dietary guidelines and physical activity (PA) guidelines, among adolescents and adults. Materials and Methods: We evaluated the health-promoting lifestyle habits by the Health-Promoting Lifestyle Profile (HPLP-II) at baseline and following 6–8 weeks post-education in a nationally representative sample of Serbian adolescents and adults (n = 3822). Results: The percentage of adolescents eating 3–5 servings of vegetables per day increased at follow-up (20.1% versus 23.1%, p = 0.001), with significantly more adolescents regularly reading food labels (from 12.2% at baseline to 14.2% at follow-up; p = 0.02). Taken together, mean HPLP-II scores in adolescents significantly improved for both diet (0.05 points; p < 0.0001) and PA (0.09 points; p < 0.0001), and for PA in adults (0.08 points; p < 0.0001). Hierarchical multiple regression analysis revealed that our model as a whole (including time of testing as a predictor variable, and age and gender as control variables) explained 3.0% of the variance in mean HPLP-II scores for diet (p = 0.942) and 3.0% for PA (p = 0.285) in adolescents, and 1.1% of the variance in HPLP-II scores for diet (p = 0.781) and 1.9% for PA (p = 0.075) in adults, respectively. Conclusions: It appears that a brief focused education can positively tackle unhealthy lifestyles in promoting good health in general population. Different modes of interactive communication used here appeared to strengthen participants’ capacities for lifestyle changes. Full article
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Open AccessArticle
The Relationship between Diffusion-Weighted Magnetic Resonance Imaging Lesions and 24-Hour Rhythm Holter Findings in Patients with Cryptogenic Stroke
Received: 25 December 2018 / Revised: 23 January 2019 / Accepted: 31 January 2019 / Published: 4 February 2019
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Abstract
Background and objectives: Cranial magnetic resonance imaging findings of patients considered to be cryptogenic stroke may be useful in determining the clinical and prognostic significance of arrhythmias, such as atrial premature beats and atrial run attacks, that are frequently encountered in rhythm Holter [...] Read more.
Background and objectives: Cranial magnetic resonance imaging findings of patients considered to be cryptogenic stroke may be useful in determining the clinical and prognostic significance of arrhythmias, such as atrial premature beats and atrial run attacks, that are frequently encountered in rhythm Holter analysis. This study was conducted to investigate the relationship between short atrial runs and frequent premature atrial contractions detected in Holter monitors and infarct distributions in cranial magnetic resonance imaging of patients diagnosed with cryptogenic stroke. Materials and Methods: We enrolled the patients with acute ischemic stroke whose etiology were undetermined. We divided the patients in two groups according to diffusion-weighted magnetic resonance imaging as single or multiple vascular territory acute infarcts. The demographic, clinical, laboratory, echocardiographic, and rhythm Holter analyses were compared. Results: The study investigated 106 patients diagnosed with cryptogenic stroke. Acute cerebral infarctions were detected in 31% of the investigated patients in multiple territories and in 69% in a single territory. In multivariate logistic regression analysis, the total premature atrial contraction count (OR = 1.002, 95% CI: 1.001–1.004, p = 0.001) and short atrial run count (OR = 1.086, 95% CI: 1.021–1.155, p = 0.008) were found as independent variables that could distinguish between infarctions in a single or in multiple vascular territories. Conclusions: Rhythm Holter monitoring of patients with infarcts detected in multiple vascular territories showed significantly higher premature atrial contractions and short atrial run attacks. More effort should be devoted to the identification of cardioembolic etiology in cryptogenic stroke patients with concurrent acute infarcts in the multiple vascular territories of the brain. Full article
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Open AccessArticle
An Innovative, Unobtrusive Approach to Investigate Smartphone Interaction in Nonaddicted Subjects Based on Wearable Sensors: A Pilot Study
Received: 18 December 2018 / Revised: 25 January 2019 / Accepted: 31 January 2019 / Published: 4 February 2019
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Abstract
Background and objectives: Smartphones are playing a pivotal role in everyday life, due to the opportunity they grant in terms of simplifying communication, entertainment, education and many other daily activities. Against such positive characteristics, smartphone interaction can result, in particular cases, in dangerous [...] Read more.
Background and objectives: Smartphones are playing a pivotal role in everyday life, due to the opportunity they grant in terms of simplifying communication, entertainment, education and many other daily activities. Against such positive characteristics, smartphone interaction can result, in particular cases, in dangerous smartphone addiction patterns, possibly leading to several long-term detrimental psychophysiological conditions. Therefore, this pilot aims at assessing the feasibility of using an innovative approach, based on unobtrusive wearable sensors, used for the first time in this specific topic, and psychological questionnaires, to investigate the links between stress and emotions in a group of young, nonaddicted individuals performing smartphone interaction. Materials and methods: 17 volunteers were enrolled for the present study. The study protocol was divided into three phases, with an initial resting state (baseline) of three minutes, a smartphone interaction session (task) of the same length, and a final resting state (recovery), lasting three minutes. In the overall procedure, electrocardiogram (ECG) and galvanic skin response (GSR) measurements, both monitored by wearable sensors, were acquired in order to assess the functioning of the autonomic nervous system (ANS). Results: A significant decrease was seen in pNN50 during the smartphone interaction with respect to the baseline (Z = −2.675, p = 0.007), whereas the Low-to-High Frequency (LF/HF) ratio at task was somewhat correlated with phubbing behaviors (r = 0.655, p = 0.029), assessed through dedicated questionnaires. Conclusions: Taken together with the slight changes in GSR data, such results suggest the feasibility of this approach to characterize the ANS activation during smartphone interaction among young individuals. Further studies should enlarge the study population and involve smartphone-addicted subjects in order to increase the scientific and clinical relevance of such findings. Full article
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Open AccessArticle
Clinical Value of Presepsin in Comparison to hsCRP as a Monitoring and Early Prognostic Marker for Sepsis in Critically Ill Patients
Received: 31 December 2018 / Revised: 24 January 2019 / Accepted: 30 January 2019 / Published: 2 February 2019
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Abstract
Background and objectives: Sepsis carries a poor prognosis for critically ill patients, even withintensive management. We aimed to determined early predictors of sepsis-related in-hospital mortality and to monitor levels of presepsin and high sensitivity C reactive protein (hsCRP) during admission relative to the [...] Read more.
Background and objectives: Sepsis carries a poor prognosis for critically ill patients, even withintensive management. We aimed to determined early predictors of sepsis-related in-hospital mortality and to monitor levels of presepsin and high sensitivity C reactive protein (hsCRP) during admission relative to the applied treatment and the development of complications. Materials and Methods: An observational study was conducted on 68 intensive care unit (ICU) patients with sepsis. Blood samples from each patient were collected at admission (day 0) for measuring presepsin, hsCRP, biochemical examination, complete blood picture and microbiological culture and at the third day (day 3) for measuring presepsin and hsCRP. Predictors of sepsis-related in-hospital mortality were assessed using regression analysis. Predictive abilities of presepsin and hsCRP were compared using the area under a receiver operating characteristic curve. The Kaplan–Meier method was used to estimate the overall survival rate. Results: Results showed that the sepsis-related in-hospital mortality was 64.6%. The day 0 presepsin and SOFA scores were associated with this mortality. Presepsin levels were significantly higher at days 0 and 3 in non-survivors vs. survivors (p = 0.03 and p < 0.001 respectively) and it decreased over the three days in survivors. Presepsin had a higher prognostic accuracy than hsCRP at all the evaluated times. Conclusions: Overall, in comparison with hsCRP, presepsin was an early predictor of sepsis-related in-hospital mortality in ICU patients. Changes in presepsin concentrations over time may be useful for sepsis monitoring, which in turn could be useful for stratifying high-risk patients on ICU admission that benefit from intensive treatment. Full article
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Open AccessArticle
CHA2DS2-VASc Score as an Independent Predictor of Suboptimal Reperfusion and Short-Term Mortality after Primary PCI in Patients with Acute ST Segment Elevation Myocardial Infarction
Received: 9 January 2019 / Revised: 18 January 2019 / Accepted: 22 January 2019 / Published: 1 February 2019
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Abstract
Background and objectives: We aimed to demonstrate the clinical utility of CHA2DS2-VASc score in risk assessment of patients with STEMI regarding adverse clinical outcomes particularly no-reflow phenomenon. Materials and Methods: We designed a retrospective cohort study using the data of Tehran [...] Read more.
Background and objectives: We aimed to demonstrate the clinical utility of CHA2DS2-VASc score in risk assessment of patients with STEMI regarding adverse clinical outcomes particularly no-reflow phenomenon. Materials and Methods: We designed a retrospective cohort study using the data of Tehran Heart Center registry for acute coronary syndrome. The study included 1331 consecutive patients with STEMI who underwent primary angioplasty. Patients were divided into two groups according to low and high CHA2DS2-VASc score. Angiographic results of reperfusion were inspected to evaluate the association of high CHA2DS2-VASc score and the likelihood of suboptimal TIMI flow. The secondary endpoint of the study was short-term in-hospital mortality of all cause. Results: The present study confirmed that CHA2DS2-VASc model enables us to determine the risk of no-reflow and all-cause in-hospital mortality independently. Odds ratios were 1.59 (1.30–2.25) and 1.60 (1.17–2.19), respectively. Moreover, BMI, high thrombus grade, and cardiogenic shock were predictors of failed reperfusion (odds were 1.07 (1.01–1.35), 1.59 (1.28–1.76), and 8.65 (3.76–24.46), respectively). We showed that using a cut off value of ≥ two in CHA2DS2-VASc model provides a sensitivity of 69.7% and specificity of 64.4% for discrimination of increased mortality hazards. Area under the curve: 0.72 with 95% CI (0.62–0.81). Conclusions: Calculation of CHA2DS2-VASc score applied as a simple risk stratification tool before primary PCI affords great predictive power. Furthermore, incremental values are obtained by using both CHA2DS2-VASc and no-reflow regarding mortality risk assessment. Full article
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Open AccessArticle
The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma
Received: 19 January 2019 / Accepted: 29 January 2019 / Published: 1 February 2019
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Abstract
Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic [...] Read more.
Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients’ gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma. Full article
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Open AccessArticle
Colistin Use in Patients with Extreme Renal Function: From Dialysis to Augmented Clearance
Received: 2 January 2019 / Revised: 20 January 2019 / Accepted: 28 January 2019 / Published: 31 January 2019
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Abstract
Background and objectives: Colistin is used for the treatment of multidrug-resistant (MDR) Gram-negative bacteria infection in critically ill patients. It is recommended to adjust the dose in cases of renal impairment but not in cases of augmented renal clearance (ARC). The aim of [...] Read more.
Background and objectives: Colistin is used for the treatment of multidrug-resistant (MDR) Gram-negative bacteria infection in critically ill patients. It is recommended to adjust the dose in cases of renal impairment but not in cases of augmented renal clearance (ARC). The aim of this study was to determine colistin use pattern in patients with different renal functional states. Materials and Methods: Adult patients admitted to intensive care units of single Latvian hospitals in the years 2015–2017 with an MDR Gram-negative bacterial infection and at least 72 h colistin therapy were included in this study. Data were collected retrospectively from medical notes. Colistin use pattern and outcomes were analyzed in patients with different renal function prior to colistin therapy: normal, ARC, impaired, and on renal replacement therapy (RRT). Results: 100 cases of colistin use met the inclusion criteria. The study group was heterogeneous, and patients had different renal function states prior to colistin therapy-from continuous RRT (18 cases) to ARC (16 cases). The standard colistin dose of 9 million units (MU) daily was the most common dose among the patients. In many cases (43%), colistin dose adjustment did not follow the recent recommendations of drug manufacturers-this was mainly in patients with renal impairment prior to colistin therapy. Eighteen cases of colistin acute kidney injury (AKI) were detected, mostly (10 cases) in patients with normal renal function and without ARC prior to colistin therapy. No patients with colistin AKI needed RRT. Conclusions: Colistin doses varied greatly among patients, and in patients with renal function impairment it was commonly not in accordance with the summary of product characteristics (SPC). Patients with ARC mostly received a standard colistin daily dose of 9 MU daily, but the cumulative dose had a tendency to be higher and duration of colistin therapy was longer in comparison with other patient groups. ARC’s role in the development of colistin nephrotoxicity is still unclear. Full article
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Open AccessArticle
Creation and Evaluation of a Preoperative Education Website for Hip and Knee Replacement Patients—A Pilot Study
Received: 13 January 2019 / Revised: 27 January 2019 / Accepted: 28 January 2019 / Published: 30 January 2019
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Abstract
Background and Objectives: There is limited research on the question of whether web-based preoperative education can improve surgical patient outcomes. The purpose of this pilot study was to determine the usability, utility, and feasibility of a website created to increase engagement and [...] Read more.
Background and Objectives: There is limited research on the question of whether web-based preoperative education can improve surgical patient outcomes. The purpose of this pilot study was to determine the usability, utility, and feasibility of a website created to increase engagement and improve the quality of the preoperative education that patients having hip and knee arthroplasty surgery receive. Materials and Methods: A website was created, and its appearance was designed with evidence-based “menu-driven” drop-downs to make the screen options age-appropriate to the patient population; the content was supported with video and PDFs of educational material, the same or similar to the usual education provided to patients. The patient-specific outcomes included qualitative data regarding patient knowledge, satisfaction, utilities, and usability. These objectives were assessed based on the perceived health website usability questionnaire online survey. Eighty patients who met inclusion criteria were recruited, ranging in age from 40 to 65 years old. Among them, 52.5% were female, 71.25% were scheduled for knee arthroplasty, and 28.75% hip arthroplasty. The patients were randomly assigned to the paper only or website education cohorts in a 50:50 ratio. However, only 19 from each cohort participated in the survey questionnaire. Results and Conclusions: We hypothesized that findings would show that patients receiving web-based education would feel more knowledgeable about their procedure, have less anxiety, and greater satisfaction with the addition of the website content; and that nurses would report that a website could conserve nursing time and resources. The study revealed no statistically significant differences between the cohorts, with an Alpha level set at 0.05. However, survey results showed that patients using the website rated self-perceived increase in knowledge, and their satisfaction in the time to find and review the information was higher than that of the paper-only cohort. The nursing survey revealed that website education improved workflow, efficiency, and patient education. Full article
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Open AccessArticle
Timing of Decompressive Craniectomy for Malignant Middle Cerebral Artery Infarction: A Single-Center Analysis
Received: 25 December 2018 / Revised: 27 January 2019 / Accepted: 28 January 2019 / Published: 30 January 2019
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Abstract
Background and aim: Malignant middle cerebral artery infarction (MMCAI) usually leads to brain edema that may result in transtentorial herniation and brainstem compression. The prognosis of MMCAI is generally poor. The aim of this study was to discuss our experience with surgical [...] Read more.
Background and aim: Malignant middle cerebral artery infarction (MMCAI) usually leads to brain edema that may result in transtentorial herniation and brainstem compression. The prognosis of MMCAI is generally poor. The aim of this study was to discuss our experience with surgical decompression for MMCAI, and determine the association between timing of craniectomy and neurological outcomes. Methods: We identified consecutive patients diagnosed with MMCAI who underwent decompressive craniectomy (DC). Clinical and demographic data were obtained from electronic medical records, including: age, sex, preoperative Glasgow Coma Scale (GCS) score, surgery timing, postoperative GCS scores, and modified Rankin Scale (mRS) scores. Results: This study included 27 stroke patients (aged 38–80 years) operated within 72 h of the onset of neurological symptoms. Sixteen, five, and six patients underwent DC within 24 h, between 24 and 48 h, and after 48 h after onset of symptoms, respectively. Five patients died after the surgery. Patients who underwent DC within 24 h and 24–48 h had better mean GCS scores than those who underwent DC after 48 h (p = 0.000, p = 0.015). In addition, patients who underwent DC within 24 h had better mean postoperative mRS scores (p = 0.000) than other patients. Patients older than 60 years had significantly lower GCS scores (p = 0.027) and higher mRS scores (p = 0.033) than younger patients. Conclusion: Our findings support that DC had satisfying outcomes in patients who underwent DC within 24 h. Older age and lower Glasgow Coma Scale scores among DC patients with MMCAI are associated with high morbidity and mortality. Full article
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Open AccessArticle
Cell Cycle Arrest and Cytotoxic Effects of SAHA and RG7388 Mediated through p21WAF1/CIP1 and p27KIP1 in Cancer Cells
Received: 5 October 2018 / Revised: 31 December 2018 / Accepted: 23 January 2019 / Published: 29 January 2019
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Abstract
Background and Objective: Alterations in gene expressions are often due to epigenetic modifications that can have a significant influence on cancer development, growth, and progression. Lately, histone deacetylase inhibitors (HDACi) such as suberoylanilide hydroxamic acid (SAHA, or vorinostat, MK0683) have been emerging [...] Read more.
Background and Objective: Alterations in gene expressions are often due to epigenetic modifications that can have a significant influence on cancer development, growth, and progression. Lately, histone deacetylase inhibitors (HDACi) such as suberoylanilide hydroxamic acid (SAHA, or vorinostat, MK0683) have been emerging as a new class of drugs with promising therapeutic benefits in controlling cancer growth and metastasis. The small molecule RG7388 (idasanutlin, R05503781) is a newly developed inhibitor that is specific for an oncogene-derived protein called MDM2, which is also in clinical trials for the treatment of various types of cancers. These two drugs have shown the ability to induce p21 expression through distinct mechanisms in MCF-7 and LNCaP cells, which are reported to have wild-type TP53. Our understanding of the molecular mechanism whereby SAHA and RG7388 can induce cell cycle arrest and trigger cell death is still evolving. In this study, we performed experiments to measure the cell cycle arrest effects of SAHA and RG7388 using MCF-7 and LNCaP cells. Materials and Methods: The cytotoxicity, cell cycle arrest, and apoptosis/necroptosis effects of the SAHA and RG7388 treatments were assessed using the Trypan Blue dye exclusion (TBDE) method, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence assay with DEVD-amc substrate, and immunoblotting methods. Results: The RG7388 treatment was able to induce cell death by elevating p21WAF1/CIP1 through inhibition of MDM2 in LNCaP, but not in MCF-7 cells, even though there was evidence of p53 elevation. Hence, we suspect that there is some level of uncoupling of p53-mediated transcriptional induction of p21WAF1/CIP1 in MCF-7 cells. Conclusion: Our results from MCF-7 and LNCaP cells confirmed that SAHA and RG7388 treatments were able to induce cell death via a combination of cell cycle arrest and cytotoxic mechanisms. We speculate that our findings could lead to the development of newer treatments for breast and prostate cancers with drug combinations including HDACi. Full article
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Open AccessArticle
Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
Received: 11 December 2018 / Revised: 21 January 2019 / Accepted: 23 January 2019 / Published: 29 January 2019
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Abstract
Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy [...] Read more.
Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy among advanced anaplastic lymphoma kinase (ALK), non-small cell lung cancer (NSCLC) patients. Materials and Methods: Randomized controlled trials comparing the use of ALK inhibitors with chemotherapy were included in this meta-analysis. We estimated the hazard ratios (HRs) and 95% confidence intervals (CI), for progression-free survival (PFS) and overall survival (OS) from a random effects model. Two-sided statistical tests were used to determine the significance of these estimates. Results: In five eligible studies (1404 patients), ALK targeted therapy, in comparison with chemotherapy, had a significantly higher PFS (HR = 0.48; 95% CI, 0.42–0.55), but not significantly higher OS (HR = 0.88; 95% CI, 0.72–1.07). Crossover from chemotherapy to ALK inhibitors was allowed after progression in all trials. The sensitivity analysis of the use of ALK inhibitors as either the first- or second-line treatment, showed improvements in PFS but not in OS. Conclusions: Our results indicate that using targeted therapy first improved PFS, but that the sequence in which the treatments were performed did not cause a significant difference in overall survival. Full article
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Open AccessCase Report
Limited Dorsal Myeloschisis with and without Type I Split Cord Malformation: Report of 3 Cases and Surgical Nuances
Received: 20 November 2018 / Revised: 21 January 2019 / Accepted: 22 January 2019 / Published: 27 January 2019
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Abstract
Limited dorsal myeloschisis (LDM) is a rare form of spina bifida which is characterized by a fibroneural stalk between the inner part of the skin and the spinal cord. It may be associated with split cord malformation (SCM). Diagnosis and management of this [...] Read more.
Limited dorsal myeloschisis (LDM) is a rare form of spina bifida which is characterized by a fibroneural stalk between the inner part of the skin and the spinal cord. It may be associated with split cord malformation (SCM). Diagnosis and management of this complex malformation is challenging. We presented 3 different cases of LDM. Two of them were associated with Type I SCM and the other had no associated malformation. All of them were evaluated radiologically just after the birth and underwent surgical treatment under intraoperative neuromonitoring. They were discharged without any complication. Newborns with spinal cystic lesions should be carefully evaluated for spinal malformations after the birth and treated surgically as soon as possible in order to prevent neurological and urological complications secondary to tethered cord syndrome. Surgical technique in LDM-SCM patients is quite different than the patients with solitary LDM. Full article
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