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J. Clin. Med., Volume 8, Issue 9 (September 2019)

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Open AccessArticle
Trajectories of Biological Values and Vital Parameters: An Observational Cohort Study of Adult Patients with Sickle Cell Disease Hospitalized for a Non-Complicated Vaso-Occlusive Crisis
J. Clin. Med. 2019, 8(9), 1502; https://doi.org/10.3390/jcm8091502 (registering DOI) - 19 Sep 2019
Abstract
Hospital admission of patients with sickle-cell disease (SCD) presenting with a vaso-occlusive crisis (VOC) can be justified by pain refractory to usual outpatient care and/or the occurrence of a complication. Yet, the trajectories of vital parameters and standard biomarkers throughout a non-complicated VOC [...] Read more.
Hospital admission of patients with sickle-cell disease (SCD) presenting with a vaso-occlusive crisis (VOC) can be justified by pain refractory to usual outpatient care and/or the occurrence of a complication. Yet, the trajectories of vital parameters and standard biomarkers throughout a non-complicated VOC has not been established. In this observational cohort study, we describe the course of routine parameters throughout 329 hospital stays for non-complicated VOC. We used a new spline-based approach to study and visualize non-specific time-dependent variables extracted from the hospital clinical data warehouse. We identified distinct trends during the VOC for hemoglobin level, leukocytes count, C-Reactive Protein (CRP) level and temperature. Hemoglobin decreased after admission and rarely returned to steady state levels before discharge. White blood cell counts were elevated at admission before immediately decreasing, whereas eosinophils increased slowly throughout the first five days of the stay. In over 95% of non-complicated VOC-related stays, the CRP value was below 100 mg/L within the first day following admission and above normal after 48 hours, and the temperature was below 38 °C throughout the entire stay. Knowing the typical trajectories of these routine parameters during non-complicated VOC may urge the clinicians to be more vigilant in case of deviation from these patterns. Full article
Open AccessEditorial
Are Oral Implants the Same As Teeth?
J. Clin. Med. 2019, 8(9), 1501; https://doi.org/10.3390/jcm8091501 (registering DOI) - 19 Sep 2019
Abstract
Osseointegration of oral implants was initially discovered by Brånemark [...] Full article
Open AccessArticle
Subtyping Lung Cancer Using DNA Methylation in Liquid Biopsies
J. Clin. Med. 2019, 8(9), 1500; https://doi.org/10.3390/jcm8091500 (registering DOI) - 19 Sep 2019
Abstract
Background: Lung cancer (LCa) is the most frequently diagnosed and lethal cancer worldwide. Histopathological subtyping, which has important therapeutic and prognostic implications, requires material collection through invasive procedures, which might be insufficient to enable definitive diagnosis. Aberrant DNA methylation is an early event [...] Read more.
Background: Lung cancer (LCa) is the most frequently diagnosed and lethal cancer worldwide. Histopathological subtyping, which has important therapeutic and prognostic implications, requires material collection through invasive procedures, which might be insufficient to enable definitive diagnosis. Aberrant DNA methylation is an early event in carcinogenesis, detectable in circulating cell-free DNA (ccfDNA). Herein, we aimed to assess methylation of selected genes in ccfDNA from LCa patients and determine its accuracy for tumor subtyping. Methods: Methylation levels of APC, HOXA9, RARβ2, and RASSF1A were assessed in three independent study groups (study group #1: 152 tissue samples; study group #2: 129 plasma samples; study group #3: 28 benign lesions of lung) using quantitative methylation-specific PCR. Associations between gene promoter methylation levels and LCa subtypes were evaluated using non-parametric tests. Receiver operating characteristic (ROC) curve analysis was performed. Results: In study group #2, HOXA9 and RASSF1A displayed higher methylation levels in small-cell lung cancer (SCLC) than in non-small-cell lung cancer (NSCLC). HOXA9 displayed high sensitivity (63.8%), whereas RASSF1A disclosed high specificity (96.2%) for SCLC detection in ccfDNA. Furthermore, HOXA9 methylation levels showed to be higher in squamous cell carcinoma in comparison with adenocarcinoma in study group #1. Conclusions: Methylation level assessments in ccfDNA may provide a minimally invasive procedure for LCa subtyping, complementing standard diagnostic procedures. Full article
(This article belongs to the Special Issue Liquid Biopsies in Lung Cancer)
Open AccessArticle
An Early, Universal Mediterranean Diet-Based Intervention in Pregnancy Reduces Cardiovascular Risk Factors in the “Fourth Trimester”
J. Clin. Med. 2019, 8(9), 1499; https://doi.org/10.3390/jcm8091499 (registering DOI) - 19 Sep 2019
Abstract
An early antenatal dietary intervention could play an important role in the prevention of metabolic diseases postpartum. The aim of this study is to evaluate whether an early, specific dietary intervention reduces women’s cardiovascular risk in the “fourth trimester”. This prospective cohort study [...] Read more.
An early antenatal dietary intervention could play an important role in the prevention of metabolic diseases postpartum. The aim of this study is to evaluate whether an early, specific dietary intervention reduces women’s cardiovascular risk in the “fourth trimester”. This prospective cohort study compares 1675 women from the standard-care group (ScG/n = 676), who received standard-care dietary guidelines, with the intervention group (IG/n = 999), who received Mediterranean diet (MedDiet)-based dietary guidelines, supplemented with extra-virgin olive oil and nuts. Cardiovascular risk was determined by the presence of metabolic syndrome (MetS) and insulin resistance syndrome (IrS) (HOMA-IR 3.5) at 12–14 weeks postpartum. MetS was less frequent in the IG (11.3 vs. 19.3%, p < 0.05). The intervention was associated with a reduction in the relative risk of having MetS: 0.74 (95% CI, 0.60–0.90), but not in the risk of IrS. When analyzing the presence of having one or more components of the MetS, the IG had significantly higher rates of having 0 components and lower rates of having ≥1 (p-trend = 0.029). An early MedDiet-based nutritional intervention in pregnancy is associated with reductions in postpartum rates of MetS. Full article
(This article belongs to the Section Epidemiology & Public Health)
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Open AccessArticle
Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies
J. Clin. Med. 2019, 8(9), 1498; https://doi.org/10.3390/jcm8091498 (registering DOI) - 19 Sep 2019
Abstract
Background: There has been a negative trend in the effectiveness of classic eradication therapy regimens for Helicobacter pylori (H. pylori), which has largely been determined from the emergence and spread of antibiotic resistance. Several studies have shown that adding rebamipide to [...] Read more.
Background: There has been a negative trend in the effectiveness of classic eradication therapy regimens for Helicobacter pylori (H. pylori), which has largely been determined from the emergence and spread of antibiotic resistance. Several studies have shown that adding rebamipide to eradication regimens leads to an increase in the effectiveness of treatment. Aim: To evaluate the efficacy and safety of including rebamipide in the eradication regimens for H. pylori infection. Methods: The literature search was conducted in the MEDLINE/PubMed, EMBASE, Cochrane Central Register, Korean Medical Citation Index, and Russian Science Citation Index databases. All identified randomized controlled trials comparing rebamipide supplementation with non-rebamipide-containing eradication regimens for the treatment of H. pylori infection were included in the final analysis. Results: We identified 11 randomized controlled trials (RCTs) involving 1227 patients (631 in groups with rebamipide and 596 in groups without rebamipide). The meta-analysis showed that the addition of rebamipide to eradication regimens significantly increased the effectiveness of treatment (odds ratio (OR) 1.753, 95% confidence interval (CI) 1.312–2.333, p < 0.001). The subgroup analysis demonstrated that rebamipide significantly increased the effectiveness of eradication when added to a dual therapy regimen (OR 1.766, 95% CI: 1.167–2.495, p = 0.006); however, no significant improvement in effectiveness was observed when it was added to the triple therapy regimen (OR 1.638, 95% CI 0.833–3.219, p = 0.152). Conclusion: This meta-analysis demonstrated that the addition of rebamipide to H. pylori eradication regimens significantly increases the effectiveness of treatment. Full article
(This article belongs to the Section Gastroenterology & Hepato-Pancreato-Biliary Medicine)
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Open AccessReview
Efficacy of Different Energy Levels Used in Focused and Radial Extracorporeal Shockwave Therapy in the Treatment of Plantar Fasciitis: A Meta-Analysis of Randomized Placebo-Controlled Trials
J. Clin. Med. 2019, 8(9), 1497; https://doi.org/10.3390/jcm8091497 (registering DOI) - 19 Sep 2019
Abstract
The objective of this study was to assess the efficacy of different energy levels used in extracorporeal shockwave therapy (ESWT) in the treatment of plantar fasciitis using a systematic review and meta-analysis. We searched PubMed, Embase, and Cochrane library, from inception to March [...] Read more.
The objective of this study was to assess the efficacy of different energy levels used in extracorporeal shockwave therapy (ESWT) in the treatment of plantar fasciitis using a systematic review and meta-analysis. We searched PubMed, Embase, and Cochrane library, from inception to March 2019 for randomized controlled trials that compared ESWT with placebo in patients with plantar fasciitis. The risk of bias for selected articles was assessed based on the Cochrane Handbook Systematic Review of Interventions. The pooled data were estimated by the mean difference or odds ratio. The meta-analysis showed that the high-energy ESWT group had a better success rate than the control group only at a three-month follow-up, but no significant difference between groups was observed for the other follow-up visits (1 and 12 months). In addition, no significant differences in visual analog scale (VAS) scores between groups were observed for all the follow-up visits (one-month and three-month). On the contrary, the medium-energy ESWT group had significantly better success rates than the control group for all the follow-up visits (3, 6, and 12 months). In addition, the medium-energy ESWT group had significant improvement in VAS scores compared with the control group for all the follow-up visits (1, 3, 6, and 12 months) after removing the extreme values. The low-energy ESWT group had significant improvement in VAS scores compared with the control group for all the follow-up visits (3 and 12 months). Otherwise, focused ESWT seems to be more effective than radial ESWT when compared with the control group. Use of local anesthesia can reduce the efficacy of low- and high-energy ESWTs. Our meta-analysis suggested that medium-energy ESWT in the treatment of plantar fasciitis was more effective than the control group. A limited number of trials related to low- and high-energy ESWTs were included in our meta-analysis. More research is required to confirm the efficacy of low- and high-energy ESWTs in future studies. Full article
Open AccessArticle
Metoclopramide and Levosulpiride Use and Subsequent Levodopa Prescription in the Korean Elderly: The Prescribing Cascade
J. Clin. Med. 2019, 8(9), 1496; https://doi.org/10.3390/jcm8091496 (registering DOI) - 19 Sep 2019
Abstract
The aim of this study was to investigate the prescribing cascade phenomenon of dopaminergic drugs such as levodopa in the management of gastroprokinetic drugs induced parkinsonism. Based on the Korea National Health Insurance Service (NHIS)-Senior Cohort Database, we analyzed patients aged ≥65 years, [...] Read more.
The aim of this study was to investigate the prescribing cascade phenomenon of dopaminergic drugs such as levodopa in the management of gastroprokinetic drugs induced parkinsonism. Based on the Korea National Health Insurance Service (NHIS)-Senior Cohort Database, we analyzed patients aged ≥65 years, between 2009 and 2013, who obtained new prescriptions for levodopa through the NHIS during this period. Those who were prescribed levodopa from 2002 to 2008 were excluded, only patients who were prescribed metoclopramide and levosulpiride within 90 days of receiving the levodopa prescription were included. Those who did not receive levodopa were used as a control group for 1:3 age and sex matching. We assessed 1824 and 1197 levodopa cases for metoclopramide and levosulpiride use, respectively. The matched controls for each levodopa case were 5472 and 3591, respectively. We used conditional logistic regression to determine the odds ratio (OR) for initiation of levodopa therapy in patients using metoclopramide and levosulpiride, relative to nonusers, after adjusting for age, sex, and exposure to antipsychotic medication. Both metoclopramide (OR = 3.04; 95% confidence interval, CI, 2.46–3.77) and levosulpiride (OR = 3.32; 95% CI, 2.56–4.3) users were three times more likely to begin using medication containing levodopa, compared to nonusers. Metoclopramide and levosulpiride were frequently prescribed within 90 days of receiving a prescription for levodopa. Before prescribing levodopa, it should be considered whether the adverse event is actually a side effect caused by metoclopramide and levosulpiride. Full article
(This article belongs to the Section Pharmacology)
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Open AccessArticle
Follow-Up and Management of Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia: Review and Experience of Our Reference Centers
J. Clin. Med. 2019, 8(9), 1495; https://doi.org/10.3390/jcm8091495 (registering DOI) - 19 Sep 2019
Abstract
Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our [...] Read more.
Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed. All patients also undergo a sampling of purulent secretions sampled from the middle meatus under endoscopic view for bacteriological analysis. In our series, CT opacities were consistent in all the patients, as well as mainly partial and located in ethmoid cells (100% of patients) and in maxillary sinuses (85.4% of patients), and stayed stable over time. In the 31 patients who had purulent secretions, bacteriological culture showed at least one bacterium in 83.9% (n = 26). There was no significant difference in positive cultures for Pseudomonas aeruginosa in patients >40 years old versus those <40 (p = 0.17; Fisher). Surgical management was performed in only 19% of patients in order to improve sinonasal mechanical drainage. Our data support the hypothesis that the sinuses can be considered as a bacterial reservoir. From this retrospective study, we have introduced several changes into our routine clinical practice in our reference centers. Based on our analyses, medical and surgical treatments benefit from incorporating bacteriological information and sinonasal symptoms much more than CT scan evaluation alone. All patients now undergo systematically an annual simultaneous bacteriological sampling of the middle meatus and sputum to follow the relationship between ENT and lung disease and to help to antibiotic therapy strategy. Full article
(This article belongs to the Special Issue Prevention, Diagnosis and Management of Chronic Rhinosinusitis)
Open AccessArticle
Positron Emission Tomography Can Support the Diagnosis of Dialysis-Related Amyloidosis
J. Clin. Med. 2019, 8(9), 1494; https://doi.org/10.3390/jcm8091494 (registering DOI) - 19 Sep 2019
Abstract
Background: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential [...] Read more.
Background: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential of PET-FDG scan in the diagnosis of DRA. Methods: Forty-six dialysis patients with at least one PET scan (72 scans) were selected out 162 patients treated in 2016–2018. Subjective global assessment (SGA), malnutrition inflammation score (A), Charlson Comorbidity Index (CCI), were assessed at time of scan; 218 age-matched cases with normal kidney function were selected as controls. PET scans were read in duplicate. Carpal tunnel syndrome was considered a proxy for DRA. A composite “amyloid score” score considered each dialysis year = 1 point; carpal tunnel-DRA = 5 points per site. Logistic regression, ROC curves and a prediction model were built. Results: The prevalence of positive PET was 43.5% in dialysis, 5% in controls (p < 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel. PET sensitivity for detecting DRA was 95% (specificity 64%). Carpal tunnel was related to dialysis vintage and MIS. A positive PET scan was significantly associated with dialysis vintage, MIS and amyloid score. A prediction model to explain PET positivity combined clinical score and MIS, allowing for an AUC of 0.906 (CI: 0.813–0.962; p < 0.001). Conclusions: PET-FDG may identify DRA, and may be useful in detecting cases in which inflammation favours B2M deposition. This finding, needing large-scale confirmation, could open new perspectives in the study of DRA. Full article
(This article belongs to the Section Nephrology & Urology)
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Open AccessArticle
A New Management Technique for Symptomatic Haematomas Following Therapeutic Vacuum-Assisted Biopsy
J. Clin. Med. 2019, 8(9), 1493; https://doi.org/10.3390/jcm8091493 (registering DOI) - 19 Sep 2019
Abstract
The aim of this study was to investigate the efficacy of the vacuum-assisted biopsy (VAB) system in evacuating symptomatic haematomas after VAB excision of benign breast lesions. We retrospectively analysed the data of eight patients with symptomatic and large haematomas who were treated [...] Read more.
The aim of this study was to investigate the efficacy of the vacuum-assisted biopsy (VAB) system in evacuating symptomatic haematomas after VAB excision of benign breast lesions. We retrospectively analysed the data of eight patients with symptomatic and large haematomas who were treated with VAB evacuation between 10 and 14 days after VAB excision. Only one case underwent the procedure 24 h after VAB excision, due to the patient reporting intense pain, which was relieved after application of the technique, even though it had to be done twice. This new clinical application of the VAB system for evacuating symptomatic breast haematomas was successful in all the cases in the present study. No technique-related complications were observed. Conclusions: To the best of our knowledge, this is the first study to reveal that VAB evacuation of symptomatic haematomas is safe, effective, quick and well-tolerated by patients. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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Open AccessReview
NK Cell Plasticity in Cancer
J. Clin. Med. 2019, 8(9), 1492; https://doi.org/10.3390/jcm8091492 (registering DOI) - 19 Sep 2019
Abstract
Natural killer (NK) cells are critical immune components in controlling tumor growth and dissemination. Given their innate capacity to eliminate tumor cells without prior sensitization, NK-based therapies for cancer are actively pursued pre-clinically and clinically. However, recent data suggest that tumors could induce [...] Read more.
Natural killer (NK) cells are critical immune components in controlling tumor growth and dissemination. Given their innate capacity to eliminate tumor cells without prior sensitization, NK-based therapies for cancer are actively pursued pre-clinically and clinically. However, recent data suggest that tumors could induce functional alterations in NK cells, polarizing them to tumor-promoting phenotypes. The potential functional plasticity of NK cells in the context of tumors could lead to undesirable outcomes of NK-cell based therapies. In this review, we will summarize to-date evidence of tumor-associated NK cell plasticity and provide our insights for future investigations and therapy development. Full article
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Open AccessArticle
Management of Schneiderian Membrane Perforations during Sinus Augmentation Procedures: A Preliminary Comparison of Two Different Approaches
J. Clin. Med. 2019, 8(9), 1491; https://doi.org/10.3390/jcm8091491 - 19 Sep 2019
Abstract
Background: The aim of this study was to retrospectively analyze two different sealing techniques for sinus membrane perforations produced during sinus floor augmentation by a lateral approach. Methods: A total of 172 lateral-approach sinus floor augmentation surgeries were performed on 130 patients. Sixty-one [...] Read more.
Background: The aim of this study was to retrospectively analyze two different sealing techniques for sinus membrane perforations produced during sinus floor augmentation by a lateral approach. Methods: A total of 172 lateral-approach sinus floor augmentation surgeries were performed on 130 patients. Sixty-one membrane perforations (35%) were reported. Most of the perforations were caused by accidental membrane tearing and 16 (26%) were caused by deliberate incision for mucocele removal. In 31 perforation cases (51%), the Schneiderian membrane was sealed by suturing, while the remaining 30 cases (49%) were sealed using a low-resorption collagen membrane coverage. Results: Out of the 31 cases treated with a suture-sealing techniques, 26 (84%) were successful, presenting graft integration. Failure occurred in the other five (16%) cases. Out of the 30 perforations sealed with low-resorption collagen membranes, 28 (93%) presented successful graft integration, while two (7%) failed. Conclusions: Both surgical techniques yielded therapeutic success. Full article
(This article belongs to the Special Issue Implant Dentistry—Trends, Challenges and Innovations)
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Open AccessArticle
Impact of Hierarchy on Multidisciplinary Heart-Team Recommendations in Patients with Isolated Multivessel Coronary Artery Disease
J. Clin. Med. 2019, 8(9), 1490; https://doi.org/10.3390/jcm8091490 - 19 Sep 2019
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Abstract
Background: The Heart Team (HT) discussion has been incorporated in the current guidelines for myocardial revascularization in order to optimize treatment decisions for patients with multivessel coronary disease (MVD). There are no data in the literature, whether hierarchical issues do have an impact [...] Read more.
Background: The Heart Team (HT) discussion has been incorporated in the current guidelines for myocardial revascularization in order to optimize treatment decisions for patients with multivessel coronary disease (MVD). There are no data in the literature, whether hierarchical issues do have an impact on HT decisions. We aimed to analyze the therapeutic recommendations of the multidisciplinary “Heart Team” (HT) for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) if: (a) The head of cardiovascular surgery (HOS) and the head of cardiology (HOC) were present during the HT meeting, (b) both directors were absent, (c) only HOS or HOC was present. Methods: Retrospective analysis of all HT discussions between 2012 and 2015 in patients with isolated MVD (without any other cardiac problems requiring surgery). Results: During the study period, we analyzed 209 HT discussions in patients with isolated MVD. If neither HOS nor HOC was present at the HT discussion, the therapeutic recommendation was in 69% CABG and 31% PCI. If HOS and HOC were present in 77% CABG and 23% PCI was recommended (p = 0.34). If only HOS was present therapeutic recommendation was in 83% CABG and 17% PCI, and if only HOC was present the recommendation was in 54% CABG and 46% PCI (p < 0.0001). This difference did not attenuate during the study period. Conclusions: The hierarchy of the participating physicians significantly impacts treatment recommendations of a multidisciplinary HT in patients with isolated MVD. This impact did not attenuate after several years of Heart Team interaction. Full article
(This article belongs to the Section Cardiology)
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Open AccessReview
Challenges and Perspectives in Nutritional Counselling and Nursing: A Narrative Review
J. Clin. Med. 2019, 8(9), 1489; https://doi.org/10.3390/jcm8091489 - 18 Sep 2019
Viewed by 122
Abstract
Nutritional counselling has been recognised as the first line approach in the management of numerous chronic diseases. Though usually carried out by dietitians, nutritional counselling may be used by nurses, or other healthcare professionals to improve nutritional status and meet healthcare goals. Healthcare [...] Read more.
Nutritional counselling has been recognised as the first line approach in the management of numerous chronic diseases. Though usually carried out by dietitians, nutritional counselling may be used by nurses, or other healthcare professionals to improve nutritional status and meet healthcare goals. Healthcare professionals require training and education to facilitate a patient centred approach to effective counselling. Advances in digital technology have the potential to improve access to nutritional counselling for some patients such as those in primary care. However, caution is required to ensure that valuable interpersonal relationships are not lost, as these form the cornerstone of effective nutritional counselling. The aim of this narrative review is to explore aspects of effective nutritional counselling, including advances in e-counselling and areas where nursing input in nutritional counselling might enhance overall nutritional care. Full article
Open AccessReview
Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service
J. Clin. Med. 2019, 8(9), 1488; https://doi.org/10.3390/jcm8091488 - 18 Sep 2019
Viewed by 96
Abstract
Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans [...] Read more.
Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PACAP1-38 could either improve or impair biology. PACAP1-38 is implicated in the pathophysiology of migraine and post-traumatic stress disorder whereas an outstanding protective potential has been established in ischemia and in Alzheimer’s disease. Lastly, PACAP receptors could mediate opposing effects both in cancers and in inflammation. In the light of the above, the duration and concentrations of PACAP agents must be carefully set at any application to avoid unwanted consequences. An enormous amount of data accumulated since its discovery (1989) and the first clinical trials are dated in 2017. Thus in the field of PACAP research: “this is not the end, not even the beginning of the end, but maybe the end of the beginning.” Full article
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Open AccessArticle
The Increase of Osteoporotic Hip Fractures and Associated One-Year Mortality in Poland: 2008–2015
J. Clin. Med. 2019, 8(9), 1487; https://doi.org/10.3390/jcm8091487 - 18 Sep 2019
Viewed by 119
Abstract
Introduction: Hip fractures are a worldwide public health issue associated with significant mortality. Previous Polish studies reported an increasing trend in the number of hip fractures for both men and women, although lower than most other European countries. Materials and Methods: The Polish [...] Read more.
Introduction: Hip fractures are a worldwide public health issue associated with significant mortality. Previous Polish studies reported an increasing trend in the number of hip fractures for both men and women, although lower than most other European countries. Materials and Methods: The Polish National Database was analyzed to examine osteoporotic hip fractures in the population aged 50 and over. Hip fracture incidence, rate, one-year mortality, and postoperative length of hospitalization were analyzed using the national health system data. Hospital discharge registry ICD-10 codes were reviewed from 2008 to 2015. Results: The incidence of hip fractures increased in both women and men by 19.4% and 14.2%, respectively. The female to male fracture ratio was 2.46. Mean postoperative hospitalization decreased from 13.6 to 11.2 days. The one-year mortality ranged between 30.45% to 32.8% for men and 26.2% to 28% for women. Of note, women aged 80–89 had the highest one-year mortality, 50.7%–55.4% after femoral neck fracture and 53%–58.5% after a pertrochanteric fracture. Conclusions: Hip fractures in Poland are increasingly more prevalent in the aging population. The unfavorable trends observed in this study indicate higher annual mortality after hip fracture, compared with other European countries. Full article
(This article belongs to the Special Issue Epidemiology, Significance and Complications of Orthopaedic Trauma)
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Open AccessArticle
Wound Healing: In Vitro and In Vivo Evaluation of a Bio-Functionalized Scaffold Based on Hyaluronic Acid and Platelet-Rich Plasma in Chronic Ulcers
J. Clin. Med. 2019, 8(9), 1486; https://doi.org/10.3390/jcm8091486 - 18 Sep 2019
Viewed by 130
Abstract
Chronic ulcers are characterized by loss of substance without a normal tendency towards spontaneous healing. The Wound Bed Preparation Guideline advises that after diagnosis, the expert should correct the biological state of the ulcer micro-environment based on TIME principles (Tissue, Infection, Moisture balance, [...] Read more.
Chronic ulcers are characterized by loss of substance without a normal tendency towards spontaneous healing. The Wound Bed Preparation Guideline advises that after diagnosis, the expert should correct the biological state of the ulcer micro-environment based on TIME principles (Tissue, Infection, Moisture balance, Epidermal). There are many ways to treat such ulcers, for example through use of advanced dressings, negative pressure, surgical toilets, dermal substitutes, autologous skin grafting, and free or local flaps. In vitro and in vivo pre-clinical models hold widely acknowledged potential yet complex limitations. Tissue bioengineering could be an ideal approach to foster innovative strategies in wound healing. Our observational study reports on an in vitro and in vivo evaluation of a bio-functionalized scaffold composed of platelet-rich plasma (PRP) and hyaluronic acid (HA) used in 182 patients affected by chronic ulcers (diabetic and vascular), comparing the results with a control group of 182 patients treated with traditional dressings (HA alone). After 30 days the patients who had undergone the combined treatment (PRP + HA), showed 96.8% ± 1.5% re-epithelialization, as compared to 78.4% ± 4.4% in the control group (HA only). Within 80 days, they had 98.4% ± 1.3% re-epithelialization as compared to 87.8% ± 4.1% in the control group (HA only; p < 0.05). No local recurrence was observed during the follow-up period. PRP + HA treatment showed stronger regenerative potential in terms of epidermal proliferation and dermal renewal compared with HA alone. Full article
(This article belongs to the Section Dermatology)
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Open AccessArticle
Association between Albumin-Bilirubin Grade and Non-Protein Respiratory Quotient in Patients with Chronic Liver Diseases
J. Clin. Med. 2019, 8(9), 1485; https://doi.org/10.3390/jcm8091485 - 18 Sep 2019
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Abstract
We sought to elucidate the relationship between albumin-bilirubin (ALBI) grade and non-protein respiratory quotient (npRQ) calculated by indirect calorimetry in chronic liver disease (CLD) patients (n = 601, median age = 63 years). Factors linked to npRQ < 0.85, which is reported [...] Read more.
We sought to elucidate the relationship between albumin-bilirubin (ALBI) grade and non-protein respiratory quotient (npRQ) calculated by indirect calorimetry in chronic liver disease (CLD) patients (n = 601, median age = 63 years). Factors linked to npRQ < 0.85, which is reported to be an optimal cutoff point for the prognosis in liver cirrhosis (LC) patients, were also investigated using univariate and multivariate analyses. The median npRQ for all cases was 0.86. In total, 253 patients (42.1%) had npRQ < 0.85. The proportions of patients with npRQ < 0.85 in LC and non-LC patients were 51.9% (166/320) in LC patients and 31.0% (87/281) in non-LC patients (p < 0.0001). The median npRQ in ALBI grades 1, 2, and 3 for all cases were: 0.89, 0.85, and 0.82 (overall p < 0.0001). The proportions of patients with npRQ < 0.85 were 31.0% (71/229) in ALBI grade 1, 46.34% (152/328) in ALBI grade 2, and 68.18% (30/44) in ALBI grade 3 (overall p < 0.0001). In multivariate analyses of factors linked to npRQ < 0.85, ALBI grade 3 (p = 0.0095, hazard ratio = 3.242, ALBI grade 1 as a reference) was an independent predictor along with prothrombin time (p = 0.0139). In conclusion, ALBI grade can be a useful marker for npRQ in patients with CLDs. Full article
(This article belongs to the Section Pulmonology)
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Open AccessArticle
Radial Approach Expertise and Clinical Outcomes of Percutanous Coronary Interventions Performed Using Femoral Approach
J. Clin. Med. 2019, 8(9), 1484; https://doi.org/10.3390/jcm8091484 - 18 Sep 2019
Viewed by 118
Abstract
We sought to evaluate the impact of experience and proficiency with radial approach (RA) on clinical outcomes of percutaneous coronary interventions (PCI) performed via femoral approach (FA) in the “real-world” national registry. A total of 539 invasive cardiologists performing PCIs in 151 invasive [...] Read more.
We sought to evaluate the impact of experience and proficiency with radial approach (RA) on clinical outcomes of percutaneous coronary interventions (PCI) performed via femoral approach (FA) in the “real-world” national registry. A total of 539 invasive cardiologists performing PCIs in 151 invasive cardiology centers in Poland between 2014 and 2017 were included. Proficiency threshold was set at >300 PCIs during four consecutive years per individual operator. The majority of operators performed >75% of all PCIs via RA (449 (65.4%)), 143 (20.8%) in 50–75% of cases, 62 (9.0%) in 25–50% and only 33 (4.8%) invasive cardiologists were using RA in <25% of all PCIs. Operators with the highest proficiency in RA were associated with increased risk of periprocedural death, stroke and bleeding complications at access site during angiography via FA. Similarly, higher prevalence of periprocedural mortality during PCI with FA was observed in most experienced radial operators as compared to other groups. The detrimental effect of FA utilization by the most experienced radial operators was observed in both stable angina and acute coronary syndromes. Higher experience and utilization of RA might be linked to worse outcomes of PCIs performed via femoral artery in both stable and acute settings. Full article
(This article belongs to the Section Cardiology)
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Open AccessReview
Dimensional Accuracy and Clinical Value of 3D Printed Models in Congenital Heart Disease: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(9), 1483; https://doi.org/10.3390/jcm8091483 - 18 Sep 2019
Viewed by 115
Abstract
The aim of this paper is to summarize and evaluate results from existing studies on accuracy and clinical value of three-dimensional printed heart models (3DPHM) for determining whether 3D printing can significantly improve on how the congenital heart disease (CHD) is managed in [...] Read more.
The aim of this paper is to summarize and evaluate results from existing studies on accuracy and clinical value of three-dimensional printed heart models (3DPHM) for determining whether 3D printing can significantly improve on how the congenital heart disease (CHD) is managed in current clinical practice. Proquest, Google Scholar, Scopus, PubMed, and Medline were searched for relevant studies until April 2019. Two independent reviewers performed manual data extraction and assessed the risk of bias of the studies using the tools published on National Institutes of Health (NIH) website. The following data were extracted from the studies: author, year of publication, study design, imaging modality, segmentation software, utility of 3DPHM, CHD types, and dimensional accuracy. R software was used for the meta-analysis. Twenty-four articles met the inclusion criteria and were included in the systematic review. However, only 7 studies met the statistical requirements and were eligible for meta-analysis. Cochran’s Q test demonstrated significant variation among the studies for both of the meta-analyses of accuracy of 3DPHM and the utility of 3DPHM in medical education. Analysis of all included studies reported the mean deviation between the 3DPHM and the medical images is not significant, implying that 3DPHM are highly accurate. As for the utility of the 3DPHM, it is reported in all relevant studies that the 3DPHM improve the learning experience and satisfaction among the users, and play a critical role in facilitating surgical planning of complex CHD cases. 3DPHM have the potential to enhance communication in medical practice, however their clinical value remains debatable. More studies are required to yield a more meaningful meta-analysis. Full article
(This article belongs to the Section Cardiology)
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Open AccessArticle
Acute Kidney Injury Adjusted for Parenchymal Mass Reduction and Long-Term Renal Function after Partial Nephrectomy
J. Clin. Med. 2019, 8(9), 1482; https://doi.org/10.3390/jcm8091482 - 18 Sep 2019
Viewed by 105
Abstract
We sought to evaluate the association of postoperative acute kidney injury (AKI) adjusted for parenchymal mass reduction with long-term renal function in patients undergoing partial nephrectomy. A total of 629 patients undergoing partial nephrectomy were reviewed. Postoperative AKI was defined by the Kidney [...] Read more.
We sought to evaluate the association of postoperative acute kidney injury (AKI) adjusted for parenchymal mass reduction with long-term renal function in patients undergoing partial nephrectomy. A total of 629 patients undergoing partial nephrectomy were reviewed. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria, by using either the unadjusted or adjusted baseline serum creatinine level, accounting for renal parenchymal mass reduction. Estimated glomerular filtration rates (eGFRs) were followed up to 61 months (median 28 months) after surgery. The primary outcome was the functional change ratio (FCR) of eGFR calculated by the ratio of the most recent follow-up value, at least 24 months after surgery, to eGFR at 3–12 months after surgery. Multivariable linear regression analysis was performed to evaluate whether unadjusted or adjusted AKI was an independent predictor of FCR. As a sensitivity analysis, functional recovery at 3–12 months after surgery compared to the preoperative baseline was analyzed. Median parenchymal mass reduction was 11%. Unadjusted AKI occurred in 16.5% (104/625) and adjusted AKI occurred in 8.6% (54/629). AKI using adjusted baseline creatinine was significantly associated with a long-term FCR (β = −0.129 ± 0.026, p < 0.001), while unadjusted AKI was not. Adjusted AKI was also a significant predictor of functional recovery (β = −0.243 ± 0.106, p = 0.023), while unadjusted AKI was not. AKI adjusted for the parenchymal mass reduction was significantly associated with a long-term functional decline after partial nephrectomy. A creatinine increase due to remaining parenchymal ischemic injury may be important in order to predict long-term renal functional outcomes after partial nephrectomy. Full article
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Open AccessArticle
Hepatobiliary Complications in Children with Sickle Cell Disease: A Retrospective Review of Medical Records from 616 Patients
J. Clin. Med. 2019, 8(9), 1481; https://doi.org/10.3390/jcm8091481 - 18 Sep 2019
Viewed by 109
Abstract
Hepatobiliary complications in children with sickle cell disease (SCD) are rarely reported but can be life-threatening. We retrospectively assessed their prevalence in a cohort of 616 children followed in a French university-hospital SCD reference center. Eligibility criteria were the following: age <18 years, [...] Read more.
Hepatobiliary complications in children with sickle cell disease (SCD) are rarely reported but can be life-threatening. We retrospectively assessed their prevalence in a cohort of 616 children followed in a French university-hospital SCD reference center. Eligibility criteria were the following: age <18 years, seen at least twice with an interval of more than 6 months from January 2008 to December 2017, with all genotypes of SCD. Patients with hepatobiliary complications were identified via the local data warehouse and medical files were thoroughly reviewed. At least one hepatobiliary complication was reported in 37% of the children. The most frequent was cholelithiasis, in 25% of cases, which led to systematic screening and elective cholecystectomy in the case of gallstones. Overall, 6% of the children experienced acute sickle cell hepatic crisis, sickle cell intra-hepatic cholestasis, or acute hepatic sequestration, with severity ranging from mild liver pain and increased jaundice to multiple organ failure and death. Emergency treatment was exchange transfusion, which led to normalization of liver tests in most cases. Five children had chronic cholangiopathy, associated with auto-immune hepatitis in two cases. One needed liver transplantation, having a good outcome but with many complications. Transfusion iron load and infectious hepatitis cases were mild. Hepatotoxicity of an iron chelator was suspected to contribute to abnormal liver test results in five patients. We propose recommendations to prevent, explore, and treat hepatobiliary complications in SCD children. We underline the need for emergency exchange transfusion when acute liver failure develops and warn against liver biopsy and transplantation in this condition. Full article
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Open AccessArticle
Association between Achievement of Estimated Average Glucose Level and 6-Month Neurologic Outcome in Comatose Cardiac Arrest Survivors: A Propensity Score-Matched Analysis
J. Clin. Med. 2019, 8(9), 1480; https://doi.org/10.3390/jcm8091480 - 18 Sep 2019
Viewed by 117
Abstract
We investigated whether achieving estimated average glucose (EAG) levels versus achieving standard glucose levels (180 mg/dL) was associated with neurologic outcome in cardiac arrest survivors. This single-center retrospective observational study included adult comatose cardiac arrest survivors undergoing therapeutic hypothermia (TH) from September 2011 [...] Read more.
We investigated whether achieving estimated average glucose (EAG) levels versus achieving standard glucose levels (180 mg/dL) was associated with neurologic outcome in cardiac arrest survivors. This single-center retrospective observational study included adult comatose cardiac arrest survivors undergoing therapeutic hypothermia (TH) from September 2011 to December 2017. EAG level was calculated using HbA1c obtained after the return of spontaneous circulation (ROSC), and the mean glucose level during TH was calculated. We designated patients to the EAG or standard glucose group according to whether the mean blood glucose level was closer to the EAG level or 180 mg/dL. Patients in the EAG and standard groups were propensity score- matched. The primary outcome was the 6-month neurologic outcome. The secondary outcomes were hypoglycemia (≤70 mg/dL) and serum neuron-specific enolase (NSE) at 48 h after ROSC. Of 384 included patients, 137 (35.7%) had a favorable neurologic outcome. The EAG group had a higher favorable neurologic outcome (104/248 versus 33/136), higher incidence of hypoglycemia (46/248 versus 11/136), and lower NSE level. After propensity score matching, both groups had similar favorable neurologic outcomes (24/93 versus 27/93) and NSE levels; the EAG group had a higher incidence of hypoglycemia (21/93 versus 6/93). Achieving EAG levels was associated with hypoglycemia but not neurologic outcome or serum NSE level. Full article
(This article belongs to the Special Issue Energetic Metabolism Impairment in Brain Dysfunction)
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Open AccessArticle
Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome
J. Clin. Med. 2019, 8(9), 1479; https://doi.org/10.3390/jcm8091479 - 17 Sep 2019
Viewed by 153
Abstract
The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced [...] Read more.
The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions. Full article
(This article belongs to the Section Endocrinology & Metabolism)
Open AccessReview
Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus
J. Clin. Med. 2019, 8(9), 1478; https://doi.org/10.3390/jcm8091478 - 17 Sep 2019
Viewed by 134
Abstract
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the [...] Read more.
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the supply of metabolically active substances, in particular growth factors. Blood-derived eye drops have been used for the treatment of several ocular surface disorders, such as dry eye disease, corneal ulcer, persistent epithelial defect, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion, and limbal stem-cell deficiency. Both autologous (from patients themselves) and heterologous (from adult donors or from cord blood sampled at birth)-derived products exist, and each source has specific pros and cons. Despite an extensive literature, several issues are still under debate and the aim of this manuscript is to review the indications, preparation methods and storage, characterization of content, rationale for clinical outcomes, patient stratification, length of treatment, and rationale for repeated treatments at disease relapse. A rationale based on a “5 Ws and 2 Hs” protocol is proposed as a way of thinking, with the attempt to clarify Who, Why, When, Where, What, and How to use these treatment options. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Open AccessReview
BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression
J. Clin. Med. 2019, 8(9), 1477; https://doi.org/10.3390/jcm8091477 - 17 Sep 2019
Viewed by 127
Abstract
BK polyomavirus (BKPyV), or BKV infection, is ubiquitous and usually non-pathogenic, with subclinical infections in 80–90% of adults worldwide. BKV infection is often associated with pathology in immunocompromised individuals. BKV infection often is associated with renal impairment, including ureteral stenosis, hemorrhagic cystitis, and [...] Read more.
BK polyomavirus (BKPyV), or BKV infection, is ubiquitous and usually non-pathogenic, with subclinical infections in 80–90% of adults worldwide. BKV infection is often associated with pathology in immunocompromised individuals. BKV infection often is associated with renal impairment, including ureteral stenosis, hemorrhagic cystitis, and nephropathy. BKV infection is less commonly associated with pneumonitis, retinitis, liver disease, and meningoencephalitis. BKV is known to replicate, establish latency, undergo reactivation, and induce clinical pathology in renal tubular epithelial cells. However, recent in vitro studies support the notion that BKV has expanded tropism-targeting glomerular parenchymal cells of the human kidney, which could impact glomerular function, enhance inflammation, and serve as viral reservoirs for reactivation from latency during immunosuppression. The implications of BKV expanded tropism in the glomerulus, and how specific host and viral factors that would contribute to glomerular inflammation, cytolysis, and renal fibrosis are related to BKV associated nephropathy (BKVAN), have not been explored. The pathogenesis of BKV in human glomerular parenchymal cells is poorly understood. In this review, I examine target cell populations for BKV infectivity in the human glomerulus. Specifically, I explore the implications of BKV expanded tropism in the glomerulus with regard viral entry, replication, and dissemination via cell types exposed to BKV trafficking in glomerulus. I also describe cellular targets shown to be permissive in vitro and in vivo for BKV infection and lytic replication, the potential role that glomerular parenchymal cells play in BKV latency and/or reactivation after immunosuppression, and the rare occurrence of BKV pathology in glomerular parenchymal cells in patients with BKVAN. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessReview
Τhe Co-Existence of Obstructive Sleep Apnea and Bronchial Asthma: Revelation of a New Asthma Phenotype?
J. Clin. Med. 2019, 8(9), 1476; https://doi.org/10.3390/jcm8091476 - 16 Sep 2019
Viewed by 185
Abstract
Bronchial asthma (BA) and obstructive sleep apnea (OSA) are common respiratory obstructive diseases that may coexist. It would be interesting to study the possible influence of that coexistence on both diseases. Until now, reviews focused mainly on epidemiology. The aim of this study [...] Read more.
Bronchial asthma (BA) and obstructive sleep apnea (OSA) are common respiratory obstructive diseases that may coexist. It would be interesting to study the possible influence of that coexistence on both diseases. Until now, reviews focused mainly on epidemiology. The aim of this study was to review the literature in relation to epidemiology, pathophysiology, consequences, screening of patients, and treatment of the coexistence of OSA and BA. We pooled studies from the PubMed database from 1986 to 2019. OSA prevalence in asthmatics was found to be high, ranging from19% to 60% in non-severe BA, reaching up to 95% in severe asthma. Prevalence was correlated with the duration and severity of BA, and increased dosage of steroids taken orally or by inhalation. This high prevalence of the coexistence of OSA and BA diseases could not be a result of just chance. It seems that this coexistence is based on the pathophysiology of the diseases. In most studies, OSA seems to deteriorate asthma outcomes, and mainly exacerbates them. CPAP (continuous positive airway pressure) treatment is likely to improve symptoms, the control of the disease, and the quality of life in asthmatics with OSA. However, almost all studies are observational, involving a small number of patients with a short period of follow up. Although treatment guidelines cannot be released, we could recommend periodic screening of asthmatics for OSA for the optimal treatment of both the diseases. Full article
Open AccessArticle
Virus-Induced Asthma/Wheeze in Preschool Children: Longitudinal Assessment of Airflow Limitation Using Impulse Oscillometry.
J. Clin. Med. 2019, 8(9), 1475; https://doi.org/10.3390/jcm8091475 - 16 Sep 2019
Viewed by 159
Abstract
: Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective [...] Read more.
: Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective study, we aimed to longitudinally evaluate changes in airflow limitation and bronchodilator responsiveness in steroid-naïve four- to six-year-old children during a virus-induced wheezing episode, with IOS pulmonary resistance parameters set at 5 (R5) and 20 (R20) Hz. Moreover, feasibility and reproducibility, in addition to the diagnostic properties of these parameters were examined. Lung function was assessed every six weeks (baseline), within the first 48 hours following an acute wheezing episode (Day 0), after 10, and after 30 days. Forty-three out of 93 recruited children (4.5 ± 0.4 years old) experienced a wheezing episode during the study period. All children were able to perform the IOS effort in an acceptable and highly reproducible manner. R5 and R20 fluctuated independently of atopy, age, height, and weight. On Day 0, R5 values were significantly lower than the respective baseline values and returned to individual baseline levels within 10 days. Post-bronchodilation R5 values were similar to the baseline ones, reflecting a reversible airway obstruction on Day 0. Response to bronchodilation (ΔR5) was significantly more pronounced on Day 0. ΔR5 values lower than −20.5% had a sensitivity of 70% and a specificity of 76% and could accurately identify up to 75% of the examined preschoolers. This study provides evidence in favor of the objective utility of IOS as an easy, highly reproducible, and sensitive technique to assess clinically significant fluctuations and bronchodilation responses suggestive of airflow limitation. Reference values although necessary are suboptimal, utilizing the personal best values as personal reference is useful and reliable. Full article
Open AccessReview
Therapy of Patients with Neuroendocrine Neoplasia—Evidence-Based Approaches and New Horizons
J. Clin. Med. 2019, 8(9), 1474; https://doi.org/10.3390/jcm8091474 - 16 Sep 2019
Viewed by 132
Abstract
Neuroendocrine tumors (NETs) show low but increasing incidence and originate in multiple organs, including the pancreas, midgut, caecum, rectum, appendix, colon, and lungs. Due to their stunning genetic, histological, and clinical variability, diagnosis and treatment of NETs are challenging. In addition, low incidence [...] Read more.
Neuroendocrine tumors (NETs) show low but increasing incidence and originate in multiple organs, including the pancreas, midgut, caecum, rectum, appendix, colon, and lungs. Due to their stunning genetic, histological, and clinical variability, diagnosis and treatment of NETs are challenging. In addition, low incidence and high variability hamper the implementation of high evidence trials. Therefore, guidelines do not cover the complexity of NETs and, frequently, treatment decisions are taken by interdisciplinary tumor conferences at comprehensive cancer centers. Treatment aims are (i) control of tumor growth, (ii) symptom control, as well as (iii) the improvement of progression-free survival (PFS) and overall survival (OS). Here, we discuss high evidence trials facilitating the achievement of these treatment aims. The majority of the evidence exists for treatment with somatostatin analogue, everolimus, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, sunitinib, and telotristat. Among those, PRRT is the only treatment option that has the potential to control symptoms, stop tumor growth, and to improve PFS and OS. In contrast, only a low level of evidence exists for treatment with cytotoxic drugs such as streptozotocin and doxorubicine. Finally, we discuss novel treatment options by a combination of cytotoxic drugs, 177Lu-DOTATATE, and tyrosine kinase inhibitors to be tested in randomized prospective trials in the future. In addition, the application of innovative isotopes, such as 225Ac, for PRRT is discussed. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle
A Novel Ex Vivo System Using 3D Polymer Scaffold to Culture Circulating Tumor Cells from Breast Cancer Patients Exhibits Dynamic E-M Phenotypes
J. Clin. Med. 2019, 8(9), 1473; https://doi.org/10.3390/jcm8091473 - 16 Sep 2019
Viewed by 248
Abstract
The majority of the cancer-associated deaths is due to metastasis—the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a [...] Read more.
The majority of the cancer-associated deaths is due to metastasis—the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(ε-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45− (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial–mesenchymal transition (EMT) in CTCs for clinical association. Full article
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