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Medicina, Volume 55, Issue 11 (November 2019)

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Open AccessReview
Biomaterials in Gastroenterology: A Critical Overview
Medicina 2019, 55(11), 734; https://doi.org/10.3390/medicina55110734 (registering DOI) - 12 Nov 2019
Abstract
In spite of the large diversity of diagnostic and interventional devices associated with gastrointestinal endoscopic procedures, there is little information on the impact of the biomaterials (metals, polymers) contained in these devices upon body tissues and, indirectly, upon the treatment outcomes. Other biomaterials [...] Read more.
In spite of the large diversity of diagnostic and interventional devices associated with gastrointestinal endoscopic procedures, there is little information on the impact of the biomaterials (metals, polymers) contained in these devices upon body tissues and, indirectly, upon the treatment outcomes. Other biomaterials for gastroenterology, such as adhesives and certain hemostatic agents, have been investigated to a greater extent, but the information is fragmentary. Much of this situation is due to the paucity of details disclosed by the manufacturers of the devices. Moreover, for most of the applications in the gastrointestinal (GI) tract, there are no studies available on the biocompatibility of the device materials when in intimate contact with mucosae and other components of the GI tract. We have summarized the current situation with a focus on aspects of biomaterials and biocompatibility related to the device materials and other agents, with an emphasis on the GI endoscopic procedures. Procedures and devices used for the control of bleeding, for polypectomy, in bariatrics, and for stenting are discussed, particularly dwelling upon the biomaterial-related features of each application. There are indications that research is progressing steadily in this field, and the establishment of the subdiscipline of “gastroenterologic biomaterials” is not merely a remote projection. Upon the completion of this article, the gastroenterologist should be able to understand the nature of biomaterials and to achieve a suitable and beneficial perception of their significance in gastroenterology. Likewise, the biomaterialist should become aware of the specific tasks that the biomaterials must fulfil when placed within the GI tract, and regard such applications as both a challenge and an incentive for progressing the research in this field. Full article
Open AccessArticle
Molecular Characterization of Uropathogenic Escherichia coli Reveals Emergence of Drug Resistant O15, O22 and O25 Serogroups
Medicina 2019, 55(11), 733; https://doi.org/10.3390/medicina55110733 (registering DOI) - 11 Nov 2019
Abstract
Background and Objectives: Uropathogenic Escherichia coli (UPEC) are common pathogens causing urinary tract infections (UTIs). We aimed to investigate the relationship among clinical manifestation, serogroups, phylogenetic groups, and antimicrobial resistance among UPEC. Materials and Methods: One-hundred Escherichia coli isolates recovered from urine [...] Read more.
Background and Objectives: Uropathogenic Escherichia coli (UPEC) are common pathogens causing urinary tract infections (UTIs). We aimed to investigate the relationship among clinical manifestation, serogroups, phylogenetic groups, and antimicrobial resistance among UPEC. Materials and Methods: One-hundred Escherichia coli isolates recovered from urine and ureteral scrapings were used for the study. The prevalence of antimicrobial resistance was determined by using European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations. E. coli serogroups associated with UTI, as well as phylogenetic diversity were analyzed using multiplex PCR reactions. Results: Eighty-seven strains (87%) were isolated from females, while 13 (13%) from males. A high frequency of resistance to cephalosporins (43%) and fluoroquinolones (31%) was observed. Among UTI-associated serogroups O15 (32.8%), O22 (23.4%), and O25 (15.6%) were dominant and demonstrated elevated resistance rates. The E. coli phylogenetic group B2 was most common. These observations extended to pregnant patients with asymptomatic bacteriuria. Conclusions: Due to high rates of resistance, strategies using empirical therapy of second-generation cephalosporins and fluoroquinolones should be reconsidered in this population. Full article
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Open AccessArticle
Effects of Different Light Sources on Neural Activity of the Paraventricular Nucleus in the Hypothalamus
Medicina 2019, 55(11), 732; https://doi.org/10.3390/medicina55110732 (registering DOI) - 09 Nov 2019
Abstract
Background and Objectives: Physical function is influenced by light irradiation, and interest in the influence of light irradiation on health is high. Light signals are transmitted from the retina to the suprachiasmatic nucleus (SCN) via the retinal hypothalamic tract as non-image vision. [...] Read more.
Background and Objectives: Physical function is influenced by light irradiation, and interest in the influence of light irradiation on health is high. Light signals are transmitted from the retina to the suprachiasmatic nucleus (SCN) via the retinal hypothalamic tract as non-image vision. Additionally, the SCN projects a nerve to the paraventricular nucleus (PVN) which acts as a stress center. This study examined the influences of three different light sources on neural activity in the PVN region using two different color temperatures. Materials and Methods: Experiments were conducted using twenty-eight Institute of Cancer Research (ICR) mice (10 week old males). Three light sources were used: (1) organic light-emitting diode (OLED) lighting, (2) LED lighting, and (3) fluorescent lighting. We examined the effects of light irradiation from the three light sources using two different color temperatures (2800 K and 4000 K). Perfusion was done 60 min after light irradiation, and then the brain was removed from the mouse for an immunohistochemistry analysis. c-Fos was immunohistochemically visualized as a marker of neural activity in the PVN region. Results: The number of c-Fos-positive cells was found to be significantly lower under OLED lighting and LED lighting conditions than under fluorescent lighting at a color temperature of 2800 K, and significantly lower under OLED lighting than LED lighting conditions at a color temperature of 4000 K. Conclusions: This study reveals that different light sources and color temperatures alter the neural activity of the PVN region. These results suggest that differences in the light source or color temperature may affect the stress response. Full article
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Open AccessCase Report
A Naso-Orbito-Ethmoid (NOE) Fracture Associated with Bilateral Anterior and Posterior Frontal Sinus Wall Fractures Caused by a Horse Kick—Case Report and Short Literature Review
Medicina 2019, 55(11), 731; https://doi.org/10.3390/medicina55110731 (registering DOI) - 09 Nov 2019
Abstract
Naso-orbito-ethmoid (NOE) fractures associated with anterior and posterior frontal sinus wall fractures are among the most challenging cranio-maxillofacial injuries. These represent a major emergency, having a potentially severe clinical picture, with intracranial hemorrhage, cerebrospinal fluid (CSF) leak, meningeal lesions, pneumocephalus, contusion or laceration [...] Read more.
Naso-orbito-ethmoid (NOE) fractures associated with anterior and posterior frontal sinus wall fractures are among the most challenging cranio-maxillofacial injuries. These represent a major emergency, having a potentially severe clinical picture, with intracranial hemorrhage, cerebrospinal fluid (CSF) leak, meningeal lesions, pneumocephalus, contusion or laceration of the brain matter, coma, and in some cases death. In this article, we present the case of a 30-year-old patient with the diagnosis of NOE fracture associated with bilateral anterior and posterior frontal sinus wall fractures caused by a horse kick, with a fulminant post-traumatic alteration of the neurological status and major impairment of the midface bone architecture. Despite the severity and complexity of the case, early initiation of correct treatment both in terms of intensive care and cranio-maxillofacial surgery led to the successful rehabilitation of the neurological status, as well as to the reconstruction and redimensioning of midface architecture and, not least, to the restoration of the patient’s physiognomy. Full article
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Open AccessArticle
Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional Study
Medicina 2019, 55(11), 730; https://doi.org/10.3390/medicina55110730 - 08 Nov 2019
Abstract
Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical [...] Read more.
Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC- lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects—ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9–5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1–3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3–8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I.1.002–1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002–1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96–0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4–9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24–4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment. Full article
Open AccessArticle
Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization
Medicina 2019, 55(11), 729; https://doi.org/10.3390/medicina55110729 - 07 Nov 2019
Abstract
Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). [...] Read more.
Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). Materials and Methods: Murine CNV was induced by means of total de-epithelization and alkali burn. Mice were divided into five groups according to topical treatment: untreated control, phosphate-buffered saline (PBS), 0.1% and 0.5% rivoceranib, and 0.5% bevacizumab. CNV area and index were measured 7 and 14 days after treatment. After corneal tissues were excised at day 14, the blood and lymphatic vessels were quantified by cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) immunofluorescence, respectively. Results: After 14 days, treatment groups with 0.1% and 0.5% rivoceranib and 0.5% bevacizumab showed a decrease in CNV area and index compared with the untreated and PBS groups (all p < 0.01). Blood and lymphatic vascularization significantly decreased in the 0.5% rivoceranib and 0.5% bevacizumab groups, as measured by CD31 and LYVE1 immunofluorescence. There was no significant difference of vascularization between the 0.5% rivoceranib and bevacizumab groups. Conclusions: Topical application of rivoceranib could effectively decrease CNV equivalent to topical bevacizumab in a murine model. Full article
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Open AccessArticle
Mature miR-99a Upregulation in the Amniotic Fluid Samples from Female Fetus Down Syndrome Pregnancies: A Pilot Study
Medicina 2019, 55(11), 728; https://doi.org/10.3390/medicina55110728 - 07 Nov 2019
Abstract
Background and Objective: Although Down syndrome is the most frequent aneuploidy, its pathogenic molecular mechanisms are not yet fully understood. The aim of our study is to quantify—by qRT-PCR—the expression levels of both the mature forms and the pri-miRNAs of the microRNAs resident [...] Read more.
Background and Objective: Although Down syndrome is the most frequent aneuploidy, its pathogenic molecular mechanisms are not yet fully understood. The aim of our study is to quantify—by qRT-PCR—the expression levels of both the mature forms and the pri-miRNAs of the microRNAs resident on chromosome 21 (miR(21)) in the amniotic fluid samples from Down syndrome singleton pregnancies and to estimate the impact of the differentially expressed microRNAs on Down syndrome fetal heart and amniocytes transcriptomes. Materials and methods: We collected amniotic fluid samples harvested by trained obstetricians as part of the second trimester screening/diagnostic procedure for aneuploidies to assess the trisomy 21 status by QF-PCR and karyotyping. Next, we evaluated—by Taqman qRT-PCR—the expression levels of both the mature forms and the pri-miRNA precursors of the microRNAs resident on chromosome 21 in amniotic fluid samples from singleton Down syndrome and euploid pregnancies. Further, we combined miRWalk 3.0 microRNA target prediction with GEO DataSets analysis to estimate the impact of hsa-miR-99a abnormal expression on Down syndrome heart and amniocytes transcriptome. Results: We found a statistically significant up-regulation of the mature form of miR-99a, but not pri-miR-99a, in the amniotic fluid samples from Down syndrome pregnancies with female fetuses. GATHER functional enrichment analysis of miRWalk3.0-predicted targets from Down syndrome amniocytes and fetal hearts transcriptome GEODataSets outlined both focal adhesion and cytokine–cytokine receptor interaction signaling as novel signaling pathways impacted by miR-99a and associated with cardiac defects in female Down syndrome patients. Conclusions: The significant overexpression of miR-99a, but not pri-miR-99a, points towards an alteration of the post-transcriptional mechanisms of hsa-miR-99a maturation and/or stability in the female trisomic milieu, with a potential impact on signaling pathways important for proper development of the heart. Full article
(This article belongs to the Special Issue Clinical Embryology and Reproductive Medicine)
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Open AccessArticle
The Impact of Pulmonary Vein Anatomy on the Outcomes of Catheter Ablation for Atrial Fibrillation
Medicina 2019, 55(11), 727; https://doi.org/10.3390/medicina55110727 - 04 Nov 2019
Abstract
Background and Objectives: Prior studies have identified a number of predictors for Atrial fibrillation (AF) ablation success, including comorbidities, the type of AF, and left atrial (LA) size. Ectopic foci in the initiation of paroxysmal AF are frequently found in pulmonary veins. Our [...] Read more.
Background and Objectives: Prior studies have identified a number of predictors for Atrial fibrillation (AF) ablation success, including comorbidities, the type of AF, and left atrial (LA) size. Ectopic foci in the initiation of paroxysmal AF are frequently found in pulmonary veins. Our aim was to assess how pulmonary vein anatomy influences the recurrence of atrial fibrillation after radiofrequency catheter ablation. Materials and Methods: Eighty patients diagnosed with paroxysmal or persistent AF underwent radiofrequency catheter ablation (RFCA) between November 2016 and December 2017. All of these patients underwent computed tomography before AF ablation. PV anatomy was classified according to the presence of common PVs or accessory PVs. Several clinical and imagistic parameters were recorded. After hospital discharge, all patients were scheduled for check-up in an outpatient clinic at 3, 6, 9, and 12 months after RFCA to detect AF recurrence. Results: A total of 80 consecutive patients, aged 53.8 ± 9.6 years, 54 (67.5%) men and 26 (32.5%) women were enrolled. The majority of patients had paroxysmal AF 53 (66.3%). Regular PV anatomy (2 left PVs, 2 right PVs) was identified in 59 patients (73.7%), a left common trunk (LCT) was detected in 15 patients (18.7%), an accessory right middle pulmonary vein (RMPV) was found in 5 patients (6.25%) and one patient presented both an LCT and an RMPV. The median follow-up duration was 14 (12; 15) months. Sinus rhythm was maintained in 50 (62.5%) patients. Age, gender, antiarrhythmic drugs, and the presence of cardiac comorbidities were not predictive of AF recurrence. The diagnosis of persistent AF before RFCA was more closely associated with an increase in recurrent AF after RFCA than after paroxysmal AF (p = 0.01). Longer procedure times (>265 minutes) were associated with AF recurrence (p = 0.04). Patients with an LA volume index of over 48.5 (mL/m2) were more likely to present AF recurrence (p = 0.006). Multivariate analysis of recurrence risk showed that only the larger LA volume index and variant PV anatomy were independently associated with AF recurrence. Conclusion: The study demonstrated that an increased volume of the left atrium was the most important predictive factor for the risk of AF recurrence after catheter ablation. Variant anatomy of PV was the only other independent predictive factor associated with a higher rate of AF recurrence. Full article
Open AccessReview
Exercise Interventions for Improving Flexibility in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis
Medicina 2019, 55(11), 726; https://doi.org/10.3390/medicina55110726 - 02 Nov 2019
Abstract
Background and objectives: People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of [...] Read more.
Background and objectives: People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of this study was to conduct a systematic review and a meta-analysis aimed at identifying the characteristics and methodological quality of investigations studying the effects of exercise interventions on the flexibility levels of people with MS. Materials and Methods: Three electronic databases (MEDLINE/PubMed, SPORTDiscus and Scopus) were systematically searched up to May 2019 for intervention studies focused on the effects of exercise on the flexibility levels of people with MS. A meta-analysis, including randomized controlled trials (RCT), which reported information regarding the effects of exercise on flexibility, was also conducted. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database, and the Quality Assessment Tool for Before–After Studies, with no control group. The quality of the information reported, regarding the programs conducted, was assessed by means of the Consensus on Exercise Reporting Template (CERT) scale. Results: Seven studies, four RCTs and three uncontrolled investigations were finally selected. The methodological quality of the RCTs was considered “poor” in one study, and “good” and “excellent” in two studies and one investigation, respectively. The three uncontrolled studies showed a methodological quality between “fair” and “poor”. Following the CERT scale, four studies were graded as “high” and three as “low”. Findings from the meta-analysis indicated no significant effects on hamstring flexibility, or the range of motion in the hips, knees or ankles. Conclusions: There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following participation in physical exercise programs, but the meta-analysis did not confirm these findings. Full article
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Open AccessReview
Comparison between Magnification Techniques and Direct Vision in Thyroid Surgery: A Systematic Review and Meta-Analysis
Medicina 2019, 55(11), 725; https://doi.org/10.3390/medicina55110725 - 01 Nov 2019
Abstract
Background and Objectives: The most common complications after conventional thyroid surgery in adult patients are recurrent laryngeal nerve (RLN) injury and hypocalcemia. Magnification techniques (surgical loupes or surgical microscope) are used for identification of RLN and parathyroid glands to diminish these complications although [...] Read more.
Background and Objectives: The most common complications after conventional thyroid surgery in adult patients are recurrent laryngeal nerve (RLN) injury and hypocalcemia. Magnification techniques (surgical loupes or surgical microscope) are used for identification of RLN and parathyroid glands to diminish these complications although more evidence is necessary to assess their safety and efficacy in comparison with direct vision. Methods and Materials: Electronic databases (Pubmed, Cochrane Library, Scopus) as well as gray literature sources were searched for randomized controlled trials (RCTs) comparing the frequency of transient/permanent RLN injury and hypocalcemia after thyroid surgery by using magnification techniques and direct vision for identification of RLN and parathyroid glands until October 17, 2019. The main outcomes were transient/permanent RLN injury and hypocalcemia. For all outcomes, 95% confidence intervals (95% CI) were used. Statistical analysis was performed with RevMan 5.3. Results: Systematic review and meta-analysis included 3 RCTs with 437 patients overall. Magnification techniques did not significantly affect the risk of occurrence of transient RLN injury (OR = 0.38, 95% CI (0.11–1.35), I2 = 0%) and transient hypocalcemia (OR = 0.31, 95% CI (0.09–1.09), I2 = 23%) compared with direct vision. Included RCTs demonstrated only two patients with permanent hypocalcemia and another one with permanent RLN injury, who belonged to the direct vision group. Conclusion: The use of magnification techniques for identification of RLN and parathyroid glands seems to be as safe as direct vision. However, they do not decrease the risk of RLN injury and transient hypocalcemia after thyroid surgery compared with direct vision. Finally, further prospective research should be conducted as the sample among the studies was small. Full article
Open AccessArticle
Outcome after Interdisciplinary Treatment for Aneurysmal Subarachnoid Hemorrhage—A Single Center Experience
Medicina 2019, 55(11), 724; https://doi.org/10.3390/medicina55110724 - 01 Nov 2019
Abstract
Background and Objectives: To identify predictors of outcome after aneurysmal subarachnoid hemorrhage (aSAH) in our interdisciplinary setting. Materials and Methods: 176 patients who had been treated for aSAH by a team of neurosurgeons and neuroradiologists between 2009 and 2017 were analyzed [...] Read more.
Background and Objectives: To identify predictors of outcome after aneurysmal subarachnoid hemorrhage (aSAH) in our interdisciplinary setting. Materials and Methods: 176 patients who had been treated for aSAH by a team of neurosurgeons and neuroradiologists between 2009 and 2017 were analyzed retrospectively. Age, gender, clinical presentation according to the Hunt and Hess (H&H) grading on admission, overall clot burden, aneurysm localization, modality of aneurysm obliteration, early deterioration (ED), occurrence of vasospasm in transcranial Doppler ultrasonography, delayed cerebral ischemia (DCI), spasmolysis, decompressive craniectomy (DC), cerebrospinal fluid (CSF) shunt placement, deep vein thrombosis (DVT), pulmonary embolism (PE), severe cardiac events (SCE), mortality on Days 14, and 30 after admission, and outcome at one year after the hemorrhage according to the Glasgow Outcome Scale (GOS) were recorded. Chi square, Fisher’s exact, Welch’s t, and Wilcoxon rank sum served as statistical tests. Generalized linear models were fitted, and ordered logistic regression was performed. Results: SCE (p = 0.049) were a significant predictor of mortality at 14 days after aSAH, but not later during the first year after the hemorrhage. Clipping as opposed to coiling (p = 0.049) of ruptured aneurysms was a significant predictor of survival on Day 30 after aSAH, but not later during the first year after the hemorrhage, while coiling as opposed to clipping of ruptured aneurysms was significantly related to a lower frequency of DVT during hospitalization (p = 0.024). Aneurysms of the anterior circulation were significantly more often clipped, while aneurysms of the posterior circulation were significantly more often coiled (p < 0.001). Age over 70 years (p = 0.049), H&H grade on admission (p = 0.022), overall clot burden (p = 0.035), ED (p = 0.009), DCI (p = 0.013), DC (p = 0.0005), and CSF shunt placement (p = 0.038) proved to be predictive of long-term outcome after aSAH. Conclusion: Long-term results after clipping and coiling of ruptured aneurysms appear equal in an interdisciplinary setting that takes aneurysm localization, available staff, and equipment into account. Full article
(This article belongs to the Special Issue Stroke, Dementia and Atrial Fibrillation)
Open AccessArticle
Intratumoral Cytotoxic T-Lymphocyte Density and PD-L1 Expression Are Prognostic Biomarkers for Patients with Colorectal Cancer
Medicina 2019, 55(11), 723; https://doi.org/10.3390/medicina55110723 - 31 Oct 2019
Abstract
Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical [...] Read more.
Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01–4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50–4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28–0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14–0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95–6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC. Full article
Open AccessArticle
The Impact of Socio-Economic and Home Environmental Factors on Oral Health-Related Quality of Life Among Children Aged 11–14
Medicina 2019, 55(11), 722; https://doi.org/10.3390/medicina55110722 - 31 Oct 2019
Abstract
Background and Objectives: Oral diseases are known to negatively impact physical, functional, and emotional well-being, and thus adversely affect quality of life. The aims of the study were (1) to assess the oral health-related quality of life (OHRQoL) and (2) to explore socio-demographic, [...] Read more.
Background and Objectives: Oral diseases are known to negatively impact physical, functional, and emotional well-being, and thus adversely affect quality of life. The aims of the study were (1) to assess the oral health-related quality of life (OHRQoL) and (2) to explore socio-demographic, -economic, and -environmental factors that are associated with OHRQoL among a sample of children aged 11–14 in Saudi Arabia. Materials and Methods: A cross-sectional design was used. The Child Perceptions Questionnaire (CPQ)—a self-administered, validated, and standardized questionnaire was used to collect data on OHRQoL in four domains: oral symptoms, functional limitations, and emotional and social well-being. In addition, data were collected on home environment, socioeconomic/demographic characteristics, and oral hygiene practices of participants and their parents or adult guardians. Univariate descriptive statistics, Spearman’s correlation, and Kruskal–Wallis H and Mann–Whitney tests were used. Data were analyzed using SPSS 23 Software. Significance was set at α = 0.05. Results: In total, 534 children participated in the study (91% response rate), of which 60% were females. Twenty percent of children described their oral health as “poor” and one in every four children reported that their oral health had at least some effect on their overall well-being. Children who were male, attending public schools, and living with both parents were more likely to report poor OHRQoL. Conclusions: A considerable proportion of children aged 11–14 could discern that their oral health had some effect on their overall well-being. The results identified potential predictors of OHRQoL. Disparities in OHRQoL exist among certain sub-populations. Active efforts and local interventions are necessary to improve OHRQoL. Full article
Open AccessReview
Treatment with Statins in Elderly Patients
Medicina 2019, 55(11), 721; https://doi.org/10.3390/medicina55110721 - 30 Oct 2019
Abstract
Elderly patients are a special category of patients, due to the physiological changes induced by age, the great number of comorbidities and drug treatment and last, but not least, to the cognitive dysfunction frequently encountered in this population. Cardiovascular disease is the most [...] Read more.
Elderly patients are a special category of patients, due to the physiological changes induced by age, the great number of comorbidities and drug treatment and last, but not least, to the cognitive dysfunction frequently encountered in this population. Cardiovascular disease is the most important cause of morbidity and mortality in elderly individuals worldwide. The rate of cardiovascular events increases after 65 years in men and after 75 years in women. Myocardial infarction and stroke are the leading disorders caused by atherosclerosis, that lead to death or functional incapacity. Elderly people have a greater risk to develop atherosclerotic cardiovascular disease. The incidence and prevalence of atherosclerosis increase with age and the number of cardiovascular events is higher in elderly patients. The most efficient treatment against atherosclerosis is the treatment with statins, that has been shown to decrease the risk both of stroke and coronary artery disease in all age groups. The advantages of the treatment become evident after at least one year of treatment. Primary prevention is the most important way of preventing cardiovascular disease in elderly individuals, by promoting a healthy lifestyle and reducing the risk factors. Secondary prevention after a stroke or myocardial infarction includes mandatory a statin, to diminish the risk of a recurrent cardiovascular event. The possible side effects of statin therapy are diabetes mellitus, myopathy, and rhabdomyolysis, hepatotoxicity. The side effects of the treatment are more likely to occur in elderly patients, due to their multiple associated comorbidities and drugs that may interact with statins. In elderly people, the benefits and disadvantages of the treatment with statins should be put in balance, especially in those receiving high doses of statins. Full article
Open AccessArticle
Antioxidant Capacity of Preterm Neonates Assessed by Hydrogen Donor Value
Medicina 2019, 55(11), 720; https://doi.org/10.3390/medicina55110720 - 30 Oct 2019
Abstract
Background and objectives: Premature newborns have a number of oxidative stress-inducing disorders. Antioxidant defense is deficient in premature newborns. Hydrogen donors can be used to evaluate the non-enzymatic antioxidant defense. By measuring hydrogen donors, a group of antioxidants can be assessed: tocopherol, ascorbic [...] Read more.
Background and objectives: Premature newborns have a number of oxidative stress-inducing disorders. Antioxidant defense is deficient in premature newborns. Hydrogen donors can be used to evaluate the non-enzymatic antioxidant defense. By measuring hydrogen donors, a group of antioxidants can be assessed: tocopherol, ascorbic acid, and glutathione. These represent the most relevant group of non-enzymatic antioxidants. The main aim of this study was to evaluate the non-enzymatic antioxidant defense capacity of premature newborns by measuring hydrogen donors. Materials and Methods: We evaluated the non-enzymatic antioxidant capacity by hydrogen donor measurement in 24 premature newborns with various oxidative stress-inducing disorders and in 14 premature newborns without oxidative stress-inducing conditions. Statistical analysis was performed using the Statistica program (v. 8, StatSoft, Round Rock, TX, USA). Differences between groups were tested with Wilcoxon matched test for quantitative paired data or Mann–Whitney test for quantitative independent data. The Z test for proportions was used to compare qualitative data among subgroups. Results: Hydrogen donors in the study group had a significantly lower value on the first day of life compared to the value of the control group. Also, the hydrogen donor value in the study group was significantly lower on the first day compared to the third day of life (p < 0.05). Neonates with mild respiratory distress (14 cases) had increased hydrogen donor values on their third day of life compared to the first day of life. Conclusions: The antioxidant capacity is influenced by oxidative stress-inducing disorders. Respiratory distress influenced the hydrogen donor value and antioxidant defense. Antioxidant defense gradually improves after birth according to gestational age. Full article
Open AccessArticle
Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia
Medicina 2019, 55(11), 719; https://doi.org/10.3390/medicina55110719 - 29 Oct 2019
Abstract
Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab [...] Read more.
Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10–12). Median OS was 68 (range 47–89) months. Adverse events (AE) were mainly grade I–II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588). Full article
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Open AccessArticle
Serum Asymmetric Dimethylarginine Levels in Patients with Vasovagal Syncope
Medicina 2019, 55(11), 718; https://doi.org/10.3390/medicina55110718 - 29 Oct 2019
Abstract
Background and Objectives: Vasovagal syncope (VVS) is the most common cause of syncope and has multiple pathophysiological mechanisms. Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide (NO). In this study, we aimed to investigate the relationship between plasma ADMA levels [...] Read more.
Background and Objectives: Vasovagal syncope (VVS) is the most common cause of syncope and has multiple pathophysiological mechanisms. Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide (NO). In this study, we aimed to investigate the relationship between plasma ADMA levels and syncope during the head-up tilt (HUT) test. Materials and Methods: Overall, 97 patients were included in this study. They were above 18 years of age and were admitted to our clinic with the complaint of at least one episode of syncope consistent with VVS. The HUT test was performed in all patients. Patients were divided into the following two groups based on the HUT test results: group 1 included 57 patients with a positive HUT test and group 2 included 35 patients with a negative HUT test. Blood samples were taken before and immediately after the HUT test to measure ADMA levels. Results: No significant intergroup differences were observed concerning gender and age (female gender 68% vs 60%; mean age 24.85 ± 4.01 vs 25.62 ± 3.54 years, respectively, for groups 1 and 2). ADMA values were similar between groups 1 and 2 before the HUT test [ADMA of 958 (544–1418) vs 951 (519–1269); p = 0.794]. In the negative HUT group, no significant differences were observed in ADMA levels before and after the HUT test [ADMA of 951 (519–1269) vs 951 (519–1566); p = 0.764]. However, in the positive HUT group, ADMA levels were significantly decreased following the HUT test [pretest ADMA of 958 (544–1418) vs post-test ADMA of 115 (67–198); p < 0.001]. Conclusion: ADMA levels significantly decreased after the HUT test in patients with VVS. Full article
Open AccessArticle
Usefulness of Protocolized Point-of-Care Ultrasonography for Patients with Acute Renal Colic Who Visited Emergency Department: A Randomized Controlled Study
Medicina 2019, 55(11), 717; https://doi.org/10.3390/medicina55110717 - 28 Oct 2019
Abstract
Background and Objectives: Ultrasonography is useful in evaluating patients with renal colic and it has high sensitivity and specificity for diagnosing ureter stones by revealing hydronephrosis. We evaluated the efficacy of point-of-care ultrasonography protocol in managing patients with acute renal colic who visited [...] Read more.
Background and Objectives: Ultrasonography is useful in evaluating patients with renal colic and it has high sensitivity and specificity for diagnosing ureter stones by revealing hydronephrosis. We evaluated the efficacy of point-of-care ultrasonography protocol in managing patients with acute renal colic who visited the emergency department (ED). Materials and Methods: Between March 2019 and July 2019, patients who visited the ED because of renal colic were randomly assigned by date of visit either to the conventional group (CG), who underwent routine diagnostic work-up without ultrasonography, or to the ultrasonography group (UG), who underwent bedside ultrasonography as an initial diagnostic testing. When hydronephrosis was detected in the UG group, a confirmatory non-contrast abdomen computed tomography scan was promptly performed. The ED length of stay, complications, and missed or delayed high-risk diagnosis were evaluated. Results: In total, 128 of 147 analyzed patients were confirmed to have ureter stones. The ED length of stay was significantly lower in the UG group than in the CG group (mean 172 min; 95% confidence interval (CI): 151–194 min vs. mean 234 min; 95% CI: 216–252 min). The medical cost was also remarkably lower in the UG group than in the CG group (259 USD vs. 319 USD; p < 0.001). The incidence of complications within 30 days after visiting ED and missed or delayed high-risk diagnosis were not significantly different between the two groups. Conclusions: We found that protocolized point-of-care ultrasonography in patients with acute renal colic who visited the ED can more effectively reduce the length of stay and medical cost without 30-day complication than usual clinical practice. Full article
(This article belongs to the Section Emergency Medicine)
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Open AccessArticle
Pleurotus highking Mushroom Induces Apoptosis by Altering the Balance of Proapoptotic and Antiapoptotic Genes in Breast Cancer Cells and Inhibits Tumor Sphere Formation
Medicina 2019, 55(11), 716; https://doi.org/10.3390/medicina55110716 - 28 Oct 2019
Abstract
Background and objectives: Mushrooms that have medicinal properties are part of many traditional diets. The aim of the present study was to use the human breast cancer cell line MCF-7 to investigate the anticancer activity of Pleurotus highking mushroom purified extract fraction-III [...] Read more.
Background and objectives: Mushrooms that have medicinal properties are part of many traditional diets. The aim of the present study was to use the human breast cancer cell line MCF-7 to investigate the anticancer activity of Pleurotus highking mushroom purified extract fraction-III (PEF-III) and to elucidate the possible mechanism of that activity. Materials and Methods: The effects of PEF-III on cell proliferation and viability were evaluated by a colony formation assay and an MTT assay, respectively. Cell morphological changes, annexin-V phycoerythrin and propidium iodide (PI) staining, DNA fragmentation, and caspase 3/7 activity assays were performed to determine the induction of apoptosis by PEF-III. The genes responsible for regulation of apoptosis were analyzed by means of Western blot analysis. In vitro tumor sphere formation assay was performed using a 3D sphere culture system. Results: PEF-III significantly reduced the proliferation and viability of MCF-7 cells. Cell shrinkage and rounding, and annexin-V phycoerythrin and PI staining followed by flow cytometry indicated that the cell death was due to apoptosis. Additionally, a laddering DNA pattern and increased levels of caspase-3/7 enzyme also corroborated the notion of apoptosis-mediated cell death. This incidence was further confirmed by upregulation of proapoptotic genes (p53 and its target gene, Bax) and downregulation of the expression of an antiapoptotic gene (Bcl-2). PEF-III also reduced the size and number of the tumor spheres in 3D culture conditions. Conclusions: The anticancer activity of PEF-III is due to induction of apoptosis by a shift in the balance of proapoptotic and antiapoptotic genes. Therefore, the findings of the present study may open a path to exploring potential drug candidates from the P. highking mushroom for combating breast cancer. Full article
(This article belongs to the Special Issue Complementary and Integrative Medicine)
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Open AccessArticle
Knowledge about Disease, Medication Therapy, and Related Medication Adherence Levels among Patients with Hypertension
Medicina 2019, 55(11), 715; https://doi.org/10.3390/medicina55110715 - 28 Oct 2019
Abstract
Background and Objectives: A particular problem in cardiology is poor adherence to pharmacological treatment among patients with hypertension. It is known that approximately half of these patients do not use their medications as prescribed by their doctor. Patients may choose not to follow [...] Read more.
Background and Objectives: A particular problem in cardiology is poor adherence to pharmacological treatment among patients with hypertension. It is known that approximately half of these patients do not use their medications as prescribed by their doctor. Patients may choose not to follow the doctor’s recommendations and regularly do not control their blood pressure, owing to many factors. A convenient method for measuring the level of adherence is the Morisky Medication Adherence Scale, which also provides insight into possible remedies for low adherence. We investigated their therapy, knowledge about the disease and its control, and demographic differences to assess the adherence of patients with hypertension. Materials and Methods: This was a cross-sectional observational study. Data were collected through a survey of 12 pharmacies in Latvia. The study involved 187 participants with hypertension. Results: The prevalence of non-adherence was 46.20% in Latvia. The oldest patients were the most adherent (p = 0.001, β = 0.27). The higher the self-rated extent from 0 to 10, to which the patient takes their antihypertensives exactly as instructed by their physician, the higher the level of adherence (p < 0.0001, β = 0.38), where at “0”, the patient does not follow physician instructions at all, and at “10”, the patient completely follows the physician’s instructions. Non-adherent patients tend to assess their medication-taking behavior more critically than adherent patients. The longer the patient is known to suffer from hypertension, the more adherent he or she is (p = 0.014, β = 0.19). Conclusions: Medication non-adherence among patients with hypertension is high in Latvia. Further investigations are needed to better understand the reasons for this and to establish interventions for improving patient outcomes. Full article
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Open AccessReview
Current Therapeutic Strategies in Diabetic Foot Ulcers
Medicina 2019, 55(11), 714; https://doi.org/10.3390/medicina55110714 - 25 Oct 2019
Abstract
Diabetic foot ulcers (DFUs) are the fastest growing chronic complication of diabetes mellitus, with more than 400 million people diagnosed globally, and the condition is responsible for lower extremity amputation in 85% of people affected, leading to high-cost hospital care and increased mortality [...] Read more.
Diabetic foot ulcers (DFUs) are the fastest growing chronic complication of diabetes mellitus, with more than 400 million people diagnosed globally, and the condition is responsible for lower extremity amputation in 85% of people affected, leading to high-cost hospital care and increased mortality risk. Neuropathy and peripheral arterial disease trigger deformities or trauma, and aggravating factors such as infection and edema are the etiological factors for the development of DFUs. DFUs require identifying the etiology and assessing the co-morbidities to provide the correct therapeutic approach, essential to reducing lower-extremity amputation risk. This review focuses on the current treatment strategies for DFUs with a special emphasis on tissue engineering techniques and regenerative medicine that collectively target all components of chronic wound pathology. Full article
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Open AccessArticle
Technical Factors Affecting Ultrasound Breast Tumor Size as Correlated with Pathological Type
Medicina 2019, 55(11), 713; https://doi.org/10.3390/medicina55110713 - 25 Oct 2019
Abstract
Background and Objectives: Accurate breast tumor sizing is very important in treatment planning; as a result, ultrasound (US) plays an important role in diagnosing breast masses, due to its non-magnified image and its availability. The continuous change in the disease pathogenesis of breast [...] Read more.
Background and Objectives: Accurate breast tumor sizing is very important in treatment planning; as a result, ultrasound (US) plays an important role in diagnosing breast masses, due to its non-magnified image and its availability. The continuous change in the disease pathogenesis of breast cancer and tremendous advances in US imaging technology require the continuous evaluation of this imaging modality. In this study, our aim was to determine the accuracy of US in measuring the size of breast mass, and if there is an influence of the different pathological types on this accuracy. Materials and Methods: This study contained 66 specimens of breast masses that underwent surgical excision and pathological examination of the resected masses; the mean difference between the size taken by US and the size taken by pathology was calculated to the patients as a whole and for each tumor type in this study. Results: The result was that US underestimates the size of the tumor by 0.5 cm for all pathological types, and the US size is in agreement with the pathology size. Conclusions: US is an accurate method in measuring breast lesions with a degree of underestimation that may be related to many factors such as the tumor type, size, and margins. Complementary MRI is recommended in case of ILC and architectural distortion. Full article
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Open AccessArticle
Characterization of Patients with Allergic Rhinitis to Ragweed Pollen in Two Distinct Regions of Romania
Medicina 2019, 55(11), 712; https://doi.org/10.3390/medicina55110712 - 24 Oct 2019
Abstract
Background and objectives: Ragweed pollen is a major source of allergen, which has rarely been observed in Romania until now. In this study, we evaluated the symptoms and associated factors in patients with allergic rhinitis to ragweed pollen in two distinct regions of [...] Read more.
Background and objectives: Ragweed pollen is a major source of allergen, which has rarely been observed in Romania until now. In this study, we evaluated the symptoms and associated factors in patients with allergic rhinitis to ragweed pollen in two distinct regions of Romania. Materials and Methods: We evaluated the records of patients newly diagnosed with allergic rhinitis induced by ragweed pollen in two allergological centers from North-West (NW) and Central parts of Romania between 2013 and 2015. The patients were clinically evaluated regarding disease length, presence, and severity of the allergic rhinitis symptoms and the association with other allergic manifestations (asthma and conjunctivitis). Results: The sensitization to ragweed was significantly higher in the NW part compared to the Central part (18.27% vs 4.1%, p < 0.001). More patients with monosensitization to ragweed pollen were observed in the NE center (27%) compared to the Central one (20.7%). Patients with monosensitization to ragweed pollen presented more severe forms of rhinitis (70% vs 31.5%, p = 0.02) in the NW part compared to polysensitized patients. The total symptoms score was significantly higher in patients from the Central part compared to the NW part (9.21 ± 2.01 vs 5.76 ±1.96, p < 0.001). Bronchial asthma was associated at a similar frequency to allergic rhinitis in both centers, but it was more frequently observed in monosensitized patients in the NW center. Allergic conjunctivitis was more frequently reported by patients from the Central part (75.86 vs 41.9, p = 0.02), while in the NW region it was noticed more commonly in monosensitized patients (65% vs 33.33, p = 0.02). Conclusions: Allergic rhinitis to ragweed pollen has been more frequently reported in the NW part of Romania. Patients with severe forms of rhinitis were observed in the central part, while in the NW the severe forms of disease were reported by patients with monosensitization. Ragweed pollen is intensely allergogenic and determines association of ocular and asthma symptoms. Co-sensitization increases the risk of asthma association. Full article
(This article belongs to the Special Issue Pollen Allergies)
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