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1.
I. Djuric-Filipovic Marco Caminati D. Filipovic C. Salvottini Z. Zivkovic 《Clinical and molecular allergy : CMA》2017,15(1):7
Background
Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy).Methods
7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up.Results
There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation.Conclusions
Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.2.
Christer Janson Fredrik Sundbom Peter Arvidsson Mary Kämpe 《Clinical and molecular allergy : CMA》2018,16(1):14
Background
Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population.Methods
Patients (n?=?329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy.Results
207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39?±?11 years (range 19–70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37?±?12 vs. 41?±?11 years, p?<?0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p?=?0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason.Conclusion
Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.3.
4.
Elif Erdem Ibrahim Inan Harbiyeli Hazal Boral Macit Ilkit Meltem Yagmur Reha Ersoz 《Mycopathologia》2018,183(3):521-527
Purpose
To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.Design
Retrospective case series in a tertiary university hospital.Participants
CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.Methods
The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.Main Outcome Measures
Grade of the corneal infection.Results
Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).Conclusions
The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.5.
Sonali J. Bracken Alexander J. Adami Ektor Rafti Craig M. Schramm Adam P. Matson 《Clinical and molecular allergy : CMA》2018,16(1):13
Background
Allergic asthma is an inflammatory disorder of the airways that results from inappropriate production of IgE against harmless, environmental antigens. Sequestration of free IgE using humanized IgG anti-IgE is an effective therapy for asthma and other atopic disorders. However, the status of free IgE in subjects who have naturally developed immune tolerance to inhaled antigens has not been well studied.Methods
C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) for 7 days to induce allergic airway disease (AAD) or 6 weeks to induce a state of local inhalational tolerance (LIT). Serum from AAD or LIT mice, diluted to achieve equivalent levels of total OVA-specific IgE, was used to sensitize rat basophil leukemia cells for allergen-mediated degranulation. Levels of degranulation were measured in relation to serum concentrations of free IgE and IgG anti-IgE/IgE immune complexes.Results
Serum from AAD animals induced a greater degree of basophil degranulation than serum from LIT animals. These results correlated with higher levels of free IgE in AAD animals, whereas LIT mice demonstrated a significant increase in IgG anti-IgE/IgE immune complexes relative to their diseased counterparts.Conclusions
Sequestration of free IgE by naturally occurring IgG anti-IgE may aid in the development of immune tolerance against inhaled allergens. The decrease in bioavailability of free IgE may, in turn, contribute to the overall reduction of asthma symptoms via a mechanism that mimics the therapeutic effects of humanized IgG anti-IgE.6.
Nazila Ariaee Shima Zarei Mojgan Mohamadi Farahzad Jabbari 《Clinical and molecular allergy : CMA》2017,15(1):22
Background
Spontaneous urticaria is a common allergic skin condition affecting 0.5–1% of individuals and may burden on health care expenditure or may be associated with remarkable morbidity.Aim
In this study, we measured the effect of vitamin D supplementation in patients with a diagnosis of CSU. Furthermore, quality of life and cytokine changes were evaluated.Methods
The clinical trial was conducted on 20 patients with idiopathic chronic urticaria. Vitamin D was administered orally for 8 weeks and disease activity was measured pre- and post-treatment using USS and DLQI. On the other hand expressions of IL-17, IL-10, Foxp3, and TGF-β by Real-time RT-PCR were assessed.Results
USS questionnaire showed that severity of idiopathic urticaria after the intervention, which compared with the first day reached a significant 55% reduction. The DLQI quality of life questionnaire 2 months after treatment showed 55% improvement. Along with the significant improvement of clinical symptoms, use of vitamin D increase FOXP3 gene expression and downregulation of IL-10, TGF-B, and FOXP3, IL-17, but these changes were not statistically significant.Limitation
These might happen due to lack of enrolled population in the investigation.Conclusion
Vitamin D can be used along with standard medical care and it’s a safe and cost-effective method for the treatment of chronic urticaria with deficiency of vitamin D.7.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.8.
Geoffrey A. Mueller Peter M. Thompson Eugene F. DeRose Thomas M. O’Connell Robert E. London 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):187
Background
Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated.Objective
This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine.Methods
An NMR metabolomics approach was used to measure metabolite concentrations in 26 pollen extracts. Pollen count data was analyzed from five cities to model exposure.Results
A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 µM) followed by trees (23 µM) and weeds (19 µM). Pollen count data showed that tree pollen was typically 5–10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to be only 1.1, 0.11, and 0.12 µg, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels.Conclusion
Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization.9.
M. S. Magnoni M. Caminati G. W. Canonica F. Arpinelli A. Rizzi G. Senna 《Clinical and molecular allergy : CMA》2017,15(1):11
Background
In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy.Aims and objectives
The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management.Methods
An anonymous 16 item web questionnaire was available (April–October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy.Results
One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence.Conclusions
Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.10.
11.
Objectives
To characterize biomarkers that underlie osteosarcoma (OS) metastasis based on an ego-network.Results
From the microarray data, we obtained 13,326 genes. By combining PPI data and microarray data, 10,520 shared genes were found and constructed into ego-networks. 17 significant ego-networks were identified with p < 0.05. In the pathway enrichment analysis, seven ego-networks were identified with the most significant pathway.Conclusions
These significant ego-modules were potential biomarkers that reveal the potential mechanisms in OS metastasis, which may contribute to understanding cancer prognoses and providing new perspectives in the treatment of cancer.12.
Background
Broadly, there are three main categories in pulmonary aspergillosis: chronic forms of aspergillosis; allergic bronchopulmonary aspergillosis; and invasive aspergillosis (IPA). IPA has been further subdivided into angioinvasive and airway-invasive aspergillosis. Aspergillus overlap syndromes is defined as the occurrence of more than one form aspergillus disease in a single individual.Objectives
To help clinicians correctly deal with AOS.Methods
Retrospectively study the clinical findings of nine patients presenting with AOS.Results
Four cases were diagnosed as angioinvasive aspergillosis complicated with ABPA, three cases as IPA overlap aspergilloma, and two cases as ABPA with AWIA. All the patients presented with cough and expectoration. In three patients with IPA overlap aspergilloma, two had hemoptysis, two had wheezing and fever. All of patients with IPA overlap ABPA had wheezing, dyspnea, and fever, three had sputum plugs, two had hemoptysis, and five patients had mucopurulent discharge and rhonchi in auscultation. Their total IgE ranged from 129 to 2124 IU/ml (676.5 ± 557.33 IU/ml). Fungal culture in sputum showed A. Fumigatus in three patients. All the six patients with IPA overlap ABPA applied steroid therapy and antifungal therapy. Three of them received two or more antifungal drugs successively, and three received combinational therapy. All the patients improved except one diagnosed ABPA overlap IPA.Conclusions
Clinical manifestation of AOS is not typical. Poor first-line therapeutic effects and complicated diagnosis criteria require clinicians to be aware of AOS when facing patients with aspergillosis.13.
Marta Michalczuk Beata Urban Tadeusz Porowski Anna Wasilewska Alina Bakunowicz-Łazarczyk 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):82
Introduction
Citrate is an old metabolite which is best known for the role in the Krebs cycle. Citrate is widely used in many branches of medicine. In ophthalmology citrate is considered as a therapeutic agent and an useful diagnostic tool—biomarker.Objectives
To summarize the published literature on citrate usage in the leading causes of blindness and highlight the new possibilities for this old metabolite.Methods
We conducted a systematic search of the scientific literature about citrate usage in ophthalmology up to January 2018. The reference lists of identified articles were searched for providing in-depth information.Results
This systematic review included 30 articles. The role of citrate in the leading causes of blindness is presented.Conclusions
Citrate might help inhibit cataract progression, in case of questions confirm glaucoma diagnosis or improve cornea repair treatment as adjuvant agent (therapy of ulcerating cornea after alkali injury, crosslinking procedure). However, the knowledge about possible citrate usage in ophthalmology is not widely known. Promoting recent scientific knowledge about citrate usage in ophthalmology may not only benefit of medical improvement but may also limit economic costs caused by leading causes of blindness. Further studies on citrate usage in ophthalmology should continuously be the field of scientific interest.14.
Casey Burton Honglan Shi Yinfa Ma 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):78
Introduction
Urinary pteridines are putative molecular biomarkers for noninvasive cancer screening and prognostication. Central to their translational biomarker development is the need to understand the sources and extent of their non-epidemiological variation.Objectives
This study was designed to characterize the two primary sources of urinary pteridine variance: daily variation and the effect of dietary folate.Methods
Daily variation was studied by collecting urine specimens (n = 81) three times daily for 3 days. The effect of dietary folate was investigated in a treatment study in which urine specimens (n = 168) were collected daily during a control week and a treatment week during which participants received dietary folate supplements. Measurements of six urinary pteridines were made using high-performance liquid chromatography–tandem mass spectrometry. Coefficients of variation were calculated to characterize daily variance between and within subjects, while nearest neighbor non-parametric analyses were used to identify diurnal patterns and measure dietary folate effects.Results
Daily variance was approximately 35 % RSD for both within-day and between-day periods for most pteridines. Diurnal patterns in response to circadian rhythms were similarly observed for urinary pteridines. Folate supplementation was shown to alter urinary pteridine profiles in a pathway dependent manner, suggesting that dietary folate may regulate endogenous neopterin and biopterin biosynthesis.Conclusions
Urinary pteridine levels were found to be responsive to both daily variation and folate supplementation. These findings provide new insights into pteridine biosynthesis and regulation as well as useful information for the design of future clinical translational research.15.
Background
An understanding of the needs and behaviors of asthma patients is important in developing an asthma-related healthcare policy. The primary goal of the present review was to assess patient perspectives on key issues in asthma and its management, as captured in patient surveys.Methods
Local, national, and multinational asthma surveys were reviewed to assess patient perspectives, and where possible healthcare provider (HCP) perspectives, on key issues, including diagnosis, treatment, control, quality of life, and other patient-centered outcomes. Twenty-four surveys, conducted or published between 1997 and 2003 in Europe and North America, were included in this review. Substantial differences among studies prevented a formal meta-analysis; instead, data were pooled to allow for general comparisons and qualitative analysis.Results
The results indicate that patients' knowledge of the underlying causes of asthma and treatment options remains inadequate. Moreover, patients often tolerate poor symptom control, possess meager knowledge of correct drug usage, and display insufficient adherence to therapy. Many patients have a low expectation of receiving an appropriate therapy or of having a positive encounter with the HCP. Among HCPs, there is evidence of inadequate understanding of disease etiology and poor or unstructured communication with patients, resulting often in inaccurate assessment of disease severity. Moreover, patients often underreport their symptoms and severity, which in turn could lead to misclassification and undertreatment.Conclusion
Improving patient education about the importance of achieving optimal asthma control, along with improved communication between patients and HCPs, emphasizing treatment options and optimal treatment of inflammation, may lead to better outcomes and improved asthma management in daily practice.16.
P. J. P. M. Cuijpers G. Bookelman W. Kicken W. de Vries A. P. M. Gorgels 《Netherlands heart journal》2016,24(7-8):456-461
Background
Integrating cardiopulmonary resuscitation (CPR) training in secondary schools will increase the number of potential CPR providers. However, currently too few certified instructors are available for this purpose. Training medical students and physical education student teachers to become CPR instructors could decrease this shortage.Aim
Examine whether medical students and physical education student teachers can provide CPR training for secondary school pupils as well as (i.?e., non-inferior to) registered nurses.Methods
A total of 144 secondary school pupils were randomly assigned to CPR training by a registered nurse (n = 12), a medical student (n = 17) or a physical education student teacher (n = 15). CPR performance was assessed after training and after eight weeks in a simulated cardiac arrest scenario on a resuscitation manikin, using manikin software and video recordings.Results
No significant differences were found between the groups on the overall Cardiff Test scores and the correctness of the CPR techniques during the post-training and retention test. All pupils showed sufficient CPR competence, even after eight weeks.Conclusion
Training by medical students or physical education student teachers is non-inferior to training by a registered nurse, suggesting that school teachers, student teachers and medical students can be recruited for CPR training in secondary schools.17.
Stephanie Blindenbach Jisca W. F. A. Vrancken Hans van der Zeijden Herre J. Reesink Folkert Brijker Martin Smalbrugge Elizabeth M. Wattel 《Tijdschrift voor gerontologie en geriatrie》2017,48(3):112-120
Introduction
Frail COPD patients are frequently not accepted for regular pulmonary rehabilitation programs due to low physical condition and functional limitations. Rehabilitation programs in nursing homes for geriatric patients with COPD have been developed. The effects of such programs are largely unknown.Aims
To assess the course of COPD-related hospital admissions and exercise tolerance in a cohort of frail COPD patients participating in geriatric COPD rehabilitation.Methods
Retrospective observational study with a follow up of 12 months after discharge from rehabilitation. COPD related hospital admission days were measured in the year before and after participating rehabilitation. Exercise tolerance was measured by the six minute walk test (6MWT) at admission and at discharge from rehabilitation.Results
Fifty-eight participants accomplished the rehabilitation program. Twelve patients died in the first year after discharge. The median number of hospital admission days in the year before participating rehabilitation was 21 (IQR 10–33). The first year after discharge this was decreased to a median of 6 (IQR 0–12). The 6MWT increased from 194 (SD 85) meters at admission to 274 (SD 95) meters at discharge (mean difference 80 m, SD 72; p < 0.05).Conclusions
Geriatric COPD rehabilitation in a nursing home setting seems to reduce hospital admissions in frail COPD patients and to increase exercise tolerance.18.
Amandine Vargas Roxane Boivin Patricia Cano Yoana Murcia Isabelle Bazin Jean-Pierre Lavoie 《Respiratory research》2017,18(1):207
Background
Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.Methods
Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied.Results
Airway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro.Conclusion
GC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.19.
Andreas Entenmann Miriam Michel Bruno Ismer Roman Gebauer 《Biomedical engineering online》2017,16(1):139
Background
R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP–VS) may be observed during routine clinical practice.Objectives
The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP–VS intervals.Methods
Calculated AP–VS intervals were compared with those predicted by experienced pediatric cardiologist.Results
A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP–VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP–VS interval could not be predicted by experienced observers. In our newly proposed technique the AP–VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (? 0.4 ms/bpm) between the two extreme levels.Conclusions
Adjusting the AP–VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP–VS interval.20.
A. F. B. E. Quast V. F. van Dijk A. A. M. Wilde R. E. Knops L. V. A. Boersma 《Netherlands heart journal》2017,25(5):312-317