Wasp stings are commonly encountered worldwide and result in a variety of clinical manifestations including local and systemic reactions. Neurological and vascular complications are rarely reported following a...
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Σάββατο 13 Οκτωβρίου 2018
Ischemic stroke following a wasp sting – a rare complication: a case report
Coverage from the American Thyroid Association® (ATA) 88th Annual Meeting
Coverage from the 88th Annual Meeting of the American Thyroid Association®
From Medscape Diabetes & Endocrinology
The post Coverage from the American Thyroid Association<sup>®</sup> (ATA) 88<sup>th</sup> Annual Meeting appeared first on American Thyroid Association.
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ATA® Announces Recipients of 2018 Special Awards
The post ATA<sup>®</sup> Announces Recipients of 2018 Special Awards appeared first on American Thyroid Association.
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News from the 88th Annual Meeting of the American Thyroid Association®
ATA 2018 Abstracts Available Online
The American Thyroid Association holds its 88th Annual Meeting at the Marriott Marquis, Washington DC from October 3-7, 2018
Thyroid Cancer Presentations at American Thyroid Association: 88th Annual Meeting
Disorders of Thyroid Function Presentations at American Thyroid Association: 88th Annual Meeting
Thyroid Nodules and Goiters Presentations at American Thyroid Association: 88th Annual Meeting
The post News from the 88<sup>th</sup> Annual Meeting of the American Thyroid Association<sup>®</sup> appeared first on American Thyroid Association.
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Coverage from the American Thyroid Association® (ATA) 88th Annual Meeting
Coverage from the 88th Annual Meeting of the American Thyroid Association®
From Medscape Diabetes & Endocrinology
The post Coverage from the American Thyroid Association<sup>®</sup> (ATA) 88<sup>th</sup> Annual Meeting appeared first on American Thyroid Association.
https://ift.tt/2Ekk1ig
ATA® Announces Recipients of 2018 Special Awards
The post ATA<sup>®</sup> Announces Recipients of 2018 Special Awards appeared first on American Thyroid Association.
https://ift.tt/2QPbVzE
News from the 88th Annual Meeting of the American Thyroid Association®
ATA 2018 Abstracts Available Online
The American Thyroid Association holds its 88th Annual Meeting at the Marriott Marquis, Washington DC from October 3-7, 2018
Thyroid Cancer Presentations at American Thyroid Association: 88th Annual Meeting
Disorders of Thyroid Function Presentations at American Thyroid Association: 88th Annual Meeting
Thyroid Nodules and Goiters Presentations at American Thyroid Association: 88th Annual Meeting
The post News from the 88<sup>th</sup> Annual Meeting of the American Thyroid Association<sup>®</sup> appeared first on American Thyroid Association.
https://ift.tt/2CIKS5M
Effect of cyclosporine coadministration on the pharmacokinetics of eltrombopag in healthy volunteers
Abstract
Purpose
Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resistance protein (BCRP) inhibitor, and can potentially alter plasma exposure to eltrombopag, a BCRP substrate. This phase 1, open-label, randomized, 3-period, crossover study evaluated the effect of cyclosporine on the pharmacokinetics of eltrombopag in healthy adults.
Methods
Thirty-nine subjects were randomized to either single dose of eltrombopag 50 mg, cyclosporine 200 mg + eltrombopag 50 mg or cyclosporine 600 mg + eltrombopag 50 mg treatment groups. Eltrombopag pharmacokinetic parameters (Cmax, tmax, AUClast, AUCinf, %AUCex, t1/2, and CL/F) were determined using noncompartmental methods.
Results
Geometric mean AUCinf, AUClast, and Cmax, were decreased by 18, 20, and 25%, respectively, for cyclosporine 200 mg + eltrombopag and by 24, 22, and 39%, respectively, for cyclosporine 600 mg + eltrombopag groups compared to the eltrombopag alone group. The median tmax was prolonged by ~ 1 h in both coadministration treatments. The geometric mean t1/2 was ≈ 21, ≈ 24, and ≈ 26 h, respectively, in cyclosporine 200 mg + eltrombopag, cyclosporine 600 mg + eltrombopag and eltrombopag alone groups. All the treatments were safe and well-tolerated. No serious adverse event or death was reported during the study.
Conclusion
These changes in exposure were not considered clinically meaningful as the dose of eltrombopag is adjusted using within-patient dose titration based on platelet counts.
https://ift.tt/2Ph6ybY
A comparison of the quality of informed consent for phase I oncology trials over a 30-year period
Abstract
Purpose
Efforts are underway in improving the informed consent process. The success of these efforts to improve quality of informed consent forms (ICFs) for phase I oncology trials has not been previously measured.
Methods
We reviewed and compared ICFs of all phase I trials for metastatic cancer conducted between 1986 and 1999 and 2000–2015 periods at our institution. Information pertaining to ICF length, study purpose description, research regimen/methods, potential risks and benefits was extracted. The reading level was assessed by Flesch–Kincaid readability tests.
Results
Of 364 ICFs screened, 310 ICFs were included in this analysis. The median length of ICFs from 1986 to 1999 and 2000–2015 was 12 and 23 pages, respectively. Only 42% (1986–1999) and 57% (2000–2015) of ICFs stated that individual participants might not benefit from treatment. Only 21% (1986–1999) and 12% (2000–2015) of all ICFs were written at ≤ 8th grade reading level. The median FRE, FKGL and GFI readability scores of ICFs from 1986 to 1999 were 53.6, 8.8, and 9.5, respectively. The median FRE, FKGL, and GFI scores of studies from 2000 to 2015 were 48.5, 10.7, and 12.4, respectively. These scores indicate that the ICF text was too hard for most people to read. The mechanism of action of the treatment, study schema/calendar, possibility of experiencing unexpected risks or death, and risks to pregnant/lactating women were not reported in a substantial number of forms.
Conclusions
Our results show that ICFs for phase I oncology trials over last 30 years have become longer, more difficult to read but are still lacking some important information.
https://ift.tt/2ORTj4N
Phase Ib study of irinotecan and ramucirumab for advanced gastric cancer previously treated with fluoropyrimidine with/without platinum and taxane
Abstract
Purpose
Optimal salvage chemotherapy for patients with treated advanced/metastatic gastric cancer (AGC) is unknown. Irinotecan is commonly used in Japan. Ramucirumab, a human IgG-1 monoclonal antibody targeting the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. We sought to determine the maximum tolerated dose (MTD) and recommended dose (RD) of ramucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platinum and taxane.
Methods
Patients received systemic chemotherapy with ramucirumab (8 mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150 mg/m2). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606).
Results
Six patients were enrolled from August 2015 to September 2017. No dose-limiting toxicity (DLT) was observed, and the maximum tolerated dose (MTD) was not reached at level 1. Irinotecan 150 mg/m2 in combination with ramucirumab 8 mg/kg was administered with acceptable toxicity, and all patients were treated at these doses. No treatment-related deaths were observed. Adverse events of Grade 3/4 were neutropenia (17%), anemia (17%) and hypertension (17%). Patients were evaluated using the RECIST criteria, and response rate and disease control rate were 17% and 83%, respectively.
Conclusions
Salvage chemotherapy with irinotecan plus ramucirumab was well-tolerated by patients previously treated for AGC. RD was defined as irinotecan 150 mg/m2 in combination with ramucirumab 8 mg/kg.
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A novel TRAIL mutant-TRAIL-Mu3 enhances the antitumor effects by the increased affinity and the up-expression of DR5 in pancreatic cancer
Abstract
Purpose
Pancreatic cancer is a malignant tumor of the digestive system with poor prognosis and high mortality, and the treatment of pancreatic cancer still remains a major challenge. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis selectively in cancer cells while causing virtually no damage to normal cells, which is promising for cancer therapy. However, many primary tumors and cancer cell lines including various human pancreatic cancer cell lines were found to be resistant to TRAIL-induced apoptosis. Therefore, the purpose of the study was to improve antitumor effect of TRAIL on pancreatic cancer.
Methods
The 114–121 amino acid coding sequence "VRERGPQR" of wild type TRAIL protein that was selected changed into "RRRRRRRR", and the novel membrane-penetrating peptide-alike mutant protein was named TRAIL-Mu3. The antitumor effect of TRAIL-Mu3 was analyzed both in vitro and in vivo. Western blotting, immunofluorescence and flow cytometry were used to investigate the underlying mechanisms.
Results
TRAIL-Mu3 could enhance the antitumor effects on pancreatic cancer cell lines, and the antitumor effect of TRAIL-Mu3 was stronger than gemcitabine in vivo. The immunofluorescence results suggested that TRAIL-Mu3 could remarkably enhance the affinity to pancreatic cancer cells. The Western blot results showed that treatment with TRAIL-Mu3 caused a clear cleavage of caspase-3 and caspase-8. In addition, both the Western blot and flow cytometry suggested a significantly up-expression of DR5 in TRAIL-Mu3 group.
Conclusions
Membrane-penetrating peptide-alike mutant-TRAIL-Mu3 induced pancreatic cancer cell death more efficiently than TRAIL, and this effect was supposed to be mediated by the increased affinity to cell membrane, the up-regulation of DR5 and the enhancement of activated caspase.
https://ift.tt/2ORT8Xb
Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET
Abstract
Purpose
This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs).
Methods
To test the hypothesis that MGMT deficiency was required for an alkylating drug response, we retrospectively reviewed the response of 13 patients with WD panNETs to alkylating agents in relation to MGMT status. We also studied MGMT expression in streptozocin resistance using panNET cell lines.
Results
The cohort included 54% of patients with and 46% without MGMT expression. Among these, 83.3% (5/6) of MGMT-negative cases showed a partial response to streptozocin. In contrast, only 14.2% (1/7) of MGMT-positive cases showed a partial response (P = 0.013). Induced expression of MGMT in BON1 cells (a panNET cell line with undetectable endogenous MGMT) produced streptozocin resistance. Knockdown of MGMT in QGP1 cells, which express MGMT endogenously, did not alter the response to streptozocin.
Conclusions
We observed a relationship between MGMT status and streptozocin response in both patients and cell culture. Despite limited cases examined, high concordance of negative expression of MGMT and response to streptozocin treatment suggest that MGMT expression can be a potential biomarker for this treatment.
https://ift.tt/2CbvlL4
Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-Kras G12D/+ ;Tp53 R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer
Abstract
Purpose
Metarrestin is a first-in-class small molecule clinical candidate capable of disrupting the perinucleolar compartment, a subnuclear structure unique to metastatic cancer cells. This study aims to define the pharmacokinetic (PK) profile of metarrestin and the pharmacokinetic/pharmacodynamic relationship of metarrestin-regulated markers.
Methods
PK studies included the administration of single or multiple dose of metarrestin at 3, 10, or 25 mg/kg via intravenous (IV) injection, gavage (PO) or with chow to wild-type C57BL/6 mice and KPC mice bearing autochthonous pancreatic tumors. Metarrestin concentrations were analyzed by UPLC–MS/MS. Pharmacodynamic assays included mRNA expression profiling by RNA-seq and qRT-PCR for KPC mice.
Results
Metarrestin had a moderate plasma clearance of 48 mL/min/kg and a large volume of distribution of 17 L/kg at 3 mg/kg IV in C57BL/6 mice. The oral bioavailability after single-dose (SD) treatment was > 80%. In KPC mice treated with SD 25 mg/kg PO, plasma AUC0–∞ of 14400 ng h/mL, Cmax of 810 ng/mL and half-life (t1/2) of 8.5 h were observed. At 24 h after SD of 25 mg/kg PO, the intratumor concentration of metarrestin was high with a mean value of 6.2 µg/g tissue (or 13 µM), well above the cell-based IC50 of 0.4 µM. At multiple dose (MD) 25 mg/kg/day PO in KPC mice, mean tissue/plasma AUC0–24h ratio for tumor, spleen and liver was 37, 30 and 31, respectively. There was a good linear relationship of dosage to AUC0–24h and C24h. AUC0–24h MD to AUC0–24h SD ratios ranged from two for liver to five for tumor indicating additional accumulation in tumors. Dose-dependent normalization of FOXA1 and FOXO6 mRNA expression was observed in KPC tumors.
Conclusions
Metarrestin is an effective therapeutic candidate with a favorable PK profile achieving excellent intratumor tissue levels in a disease with known poor drug delivery.
https://ift.tt/2OdvBAa
Effects of inhalational anti-asthmatic medications on oral health between 7 and 14 years of age
Sapna Konde, Manisha Agarwal, Rachna Chaurasia
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):70-73
Introduction: Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. The World Health Organization considers asthma as the most important chronic respiratory disease of the childhood. Aim: The aim of this study was to observe the changes in oral health and salivary pH, of asthmatic children aged between 7 and 14 years, treated with different combinations of inhaled medication. Materials and Methods: A total of 120 children aged between 7 and 14 years were divided into two groups of which 60 were asthmatic children and the rest 60 were nonasthmatic which were served as control group. Dental caries was assessed using decayed missing filled tooth (DMFT) index for permanent teeth and decayed extracted filled tooth (DEFT) index for primary teeth. Oral hygiene status was determined by simplified oral hygiene index (OHI-S) and modified (OHI-S) index for primary teeth. The resting salivary pH was estimated using pH strips and comparison was made between both groups. Results: The mean value of dental caries (DMFT and DEFT) was found to be significantly higher among study group compared to control group (P < 0.05), while for salivary pH, it was significantly lower among the study group compared to control (P < 0.05), whereas oral hygiene status was statistically not significant in relation to anti-asthmatic medications. Conclusions: Children with asthma have higher caries prevalence, lower salivary pH compared to the control group, which can be due to use of anti-asthmatics medications.
https://ift.tt/2yi3plD
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):70-73
Introduction: Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. The World Health Organization considers asthma as the most important chronic respiratory disease of the childhood. Aim: The aim of this study was to observe the changes in oral health and salivary pH, of asthmatic children aged between 7 and 14 years, treated with different combinations of inhaled medication. Materials and Methods: A total of 120 children aged between 7 and 14 years were divided into two groups of which 60 were asthmatic children and the rest 60 were nonasthmatic which were served as control group. Dental caries was assessed using decayed missing filled tooth (DMFT) index for permanent teeth and decayed extracted filled tooth (DEFT) index for primary teeth. Oral hygiene status was determined by simplified oral hygiene index (OHI-S) and modified (OHI-S) index for primary teeth. The resting salivary pH was estimated using pH strips and comparison was made between both groups. Results: The mean value of dental caries (DMFT and DEFT) was found to be significantly higher among study group compared to control group (P < 0.05), while for salivary pH, it was significantly lower among the study group compared to control (P < 0.05), whereas oral hygiene status was statistically not significant in relation to anti-asthmatic medications. Conclusions: Children with asthma have higher caries prevalence, lower salivary pH compared to the control group, which can be due to use of anti-asthmatics medications.
https://ift.tt/2yi3plD
Allergen immunotherapy: What does the future hold?
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):41-42
https://ift.tt/2yGm7mm
Future modalities in allergen immunotherapy: A brief overview
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):43-46
Allergen immunotherapy (AIT) is the only disease-modifying modality for the treatment of allergic diseases. The well-known and approved formulations are subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT) and allergoids. The drawbacks of the conventional AIT such as the risk of anaphylaxis led to the development of allergoids, Future approaches in AIT may permit (1) shorter treatment regimens, (2) improved safety, (3) improved compliance and (4) newer indications for AIT, which are discussed in the article.
https://ift.tt/2yiE5vZ
Hypersensitivity vasculitis in a young adult
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):78-81
This is a case report of a case of hypersensitive vasculitis in a young man. After a comprehensive history and analysis of his symptoms, the symptoms were triggered probably after exposure to yellow fever vaccine. The patient's symptoms were brought under control after starting on immunosuppressive medication.
https://ift.tt/2yCr8wh
A study of skin sensitivity to various allergens by skin prick test in patients of bronchial asthma and allergic rhinitis
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):47-53
Background: Bronchial asthma (BA) and allergic rhinitis (AR) are among the most common allergic disorders. Identification of specific causative allergens is of paramount importance for further management. Aims: This study aims (1) to find out the prevalence of various allergens leading to AR and/or BA through skin prick test (SPT), (2) to identify the trigger factors in these patients, (3) to study correlations of allergens and seasonal variations in patients suffering from AR and/or BA. Materials and Methods: A total of 134 patients were collected from outpatient department and inpatient department of Respiratory Medicine Department of Geetanjali Medical College and Hospital, Udaipur, from January 2016 to December 2017. The diagnosis of BA and AR was made according to the GINA and ARIA guidelines, respectively. SPT was done with 78 different types of aeroallergens, which included 23 types of pollens, 6 types of fungi, 10 types of insects, 6 types of dusts, 6 types of dander, 3 fabrics, 2 feathers, and 22 food allergens. Patients who had taken short-acting oral antihistaminics, beta-blockers, steroids, tricyclic antidepressants or any other drug that could affect the test within one week prior to testing were excluded. Also, patients on long-acting oral antihistaminics within four weeks of testing and pregnant women were excluded. Results: A total of 134 patients consisting of 73 (54.48%) males and 61 (45.52%) females, in the age group of 5–65 years, were included in the study. The maximum numbers of patients (50; 37.31%) were between the age group of 20 and 35 years. The maximum number of patients (94; 70.15%) had a duration of suffering from >1 years. AR was found in 60 (44.78%), BA associated with AR was found in 39 (29.1%), while BA alone was found in 35 (26.12%). In 54% of patients, triggers were found for exacerbation of their symptoms, the most common being air pollution (48%) followed by cold exposure (20%), physical activity (12%), irritants (9%), smoke (7%), and fumes and odors (4%). A total of 10,452 SPTs were done, out of which 265 (%) showed positive reactions. The positivity for pollens was seen in 116 (43.77%) patients followed by insects [79 (29.81%)], fungi [22 (8.3%)], house dust mite [15 (5.66%)], dusts [11 (4.15%)], fabrics [10 (3.77%)], danders [9 (3.4%)], and feathers [3 (1.13%)], respectively. Food allergens showed no significant reactions to SPT. Conclusions: Our study showed that insects were the most common allergen in BA patients, while pollens were the most common allergen in patients of AR with or without BA. Intermittent symptoms were common with pollen allergy.
https://ift.tt/2yoHKZp
Study on impact of air pollution on asthma among school going children residing in urban Agra
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):65-69
Background: Air pollution is one of the world's most serious environmental problems. Air pollution has many negative health effects on the general population, especially children, individuals with underlying chronic disease, and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in schoolgoing children in Agra, suffering from asthma compared with healthy subjects, and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms. Materials and Methods: We enrolled 702 children aged 6–18 years in this prospective study. A total of 342 children with asthma and 360 healthy subjects were monitored for 6 months from September 2013 to February 2014. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants. A total of 328 children with asthma and 345 healthy subjects completed follow-up. Results: Children with asthma reported significantly more days of fever (P <0.001) and cough (P < 0.001), episodes of rhinitis (P = 0.087), asthma attacks (P < 0.001), episodes of pneumonia (P < 0.003), and hospitalizations (P = 0.01). In the asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR] = 1.79; 95% confidence interval [CI], 1.13–2.84), whereas living near green areas was found to be protective (OR = 0.50; 95% CI, 0.31–0.80). Conclusion: There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children suffering from asthma. These findings suggest that environmental control may be crucial for respiratory health in children with the underlying respiratory disease.
https://ift.tt/2yBPZR0
Prevalence of respiratory symptoms in automobile spray painters of Mumbai: A cross-sectional study
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):54-58
Background: Spray painting poses health hazards that affect the respiratory system. During spray painting, workers are exposed to different paint components. Toluene diisocyanates, methylene diisocyanates, and hexamethylene diisocyanates are commonly used isocyanates in the spray painting. The major route of occupational exposure to isocyanates is the inhalation of the vapor or aerosol that can sensitize workers. The short- and long-term consequences of the respiratory system can be raised from these occupations. Hence, the aim and objective of this study were to find the prevalence of respiratory symptoms in automobile spray painters of Mumbai and to study the use of safety measures in automobile spray painters. Materials and Methods: The study was a cross-sectional study. A total of 50 automobile spray painters were selected based on inclusion criteria. The self-made validated questionnaire was used as an outcome measure. Results: About 90% of the automobile spray painters have reported respiratory symptoms in their occupation among which 88% had the most prevalent symptom of breathlessness followed by 84% workers had the symptom of coughing. Nearly 60% of workers were aware about the safety measures, but only 33% were using the safety measures during work. Conclusion: The study showed a high prevalence of respiratory symptoms. The lack of awareness and the use of safety measures had increased the severity of the symptoms.
https://ift.tt/2yiE0bF
Clinical, radiological, and microbiological profile of pulmonary aspergillosis in treated cases of pulmonary tuberculosis
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):74-77
Context: Clinical studies about detailed spectrum of aspergillosis in treated tuberculosis (TB) patients are lacking. Hence, a study was undertaken at the Institute of Respiratory Disease, Jaipur, Rajasthan, India. Treated patients of pulmonary TB having any symptom such as hemoptysis, cough with expectoration, weight loss, and whose chest X-ray showed residual cavitation were enrolled for the study. Aims: This study aimed to determine the prevalence of pulmonary aspergillosis in treated cases of pulmonary TB and to study the social, demographical, and clinical characteristics of these patients. Settings and Design: A descriptive type of observational study was conducted at the Department of Respiratory Medicine in a tertiary care center of Rajasthan. Subjects and Methods: This descriptive type of observational study was conducted on seventy patients, whose sputum or bronchial wash showed isolation of Aspergillus. Demographic details, predisposing factors, and clinical findings were noted. Statistical Analysis Used: Data collected were entered into Excel spreadsheet and quantitative data were expressed as number and percentage. Results: The presentation of pulmonary aspergillosis in treated cases of pulmonary TB varies from aspergilloma (57%) to chronic necrotizing pulmonary aspergillosis (36%) to allergic bronchopulmonary aspergillosis (7%). The most common symptom was recurrent hemoptysis. Most of the patients were farmers by occupation, but no significant comorbid illness was seen. X-ray chest missed about 70% of cases. The most common species were Aspergillus fumigatus; others were Aspergillus terreus (13%), Aspergillus flavus (13%), and Aspergillus niger (7%). Conclusions: All treated cases of pulmonary TB presenting with recurrent hemoptysis and/or cough with expectoration should be evaluated in detail for pulmonary aspergillosis as chest X-ray alone can miss the diagnosis.
https://ift.tt/2yB7yk4
Air pollution and respiratory dysfunction among adolescents: A case–control study from North West India
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):59-64
Introduction: Children are vulnerable to the effects of air pollution because of immature organ system and immune system. Air pollutants can lead to both upper and lower respiratory tract symptoms. Methodology: Adolescents in the age group of 10–19 years children from residential areas with established maximal and low pollution levels as reported by State Pollution Control Board were included in the study using age-, sex-, weight-, and height-matched case–control study design. For the assessment of respiratory dysfunction, the values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, and forced expiratory flow (FEF) 25%–75% were included in this study. Odds ratio with 95% confidence interval was calculated to ascertain the strength of association. Results: The distribution of abnormalities for a restrictive pattern in males in polluted group was 42% as compared to 29% in low polluted group (P = 0.007). The mean values of pulmonary function parameters FVC, FEV1, FEV1/FVC, and FEF 25%–75% (expressed as percentage of predicted values) were compared in two groups, a deficit of approximately 4.5%, 6%, 1.06%, and 3.4% was observed in males versus 4.9%, 6.3%, 2.44%, and 2.4%, respectively for females. Conclusion: There is a statistically significant difference in the pulmonary functions in the polluted versus less polluted areas with the children being affected in a harmful manner in the former areas.
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Detection of immunoglobulin A deficiency in celiac disease suspects
Indian Journal of Allergy, Asthma and Immunology 2018 32(2):82-83
https://ift.tt/2yAM9Yb
ORAL FOOD CHALLENGE FAILURES AMONG FOODS RESTRICTED DUE TO ATOPIC DERMATITIS
Recent studies have suggested that removing foods from the diet to manage atopic dermatitis (AD), based on positive allergy tests, may lead to immediate allergic reactions on reintroduction of that food.
https://ift.tt/2A7I4Nk
Within-tester repeatability and between-tester reproducibility of skin test endpoint titration: A quality assurance study
Airway response to allergen depends on two independent factors: the degree of IgE sensitivity to the allergen and the level of lower airway response as quantified by histamine or methacholine challenge.1,2 The former can be assessed by skin prick titration (SPT) to determine the skin test endpoint (STE), which for research purposes is the smallest concentration of allergen that produces a skin wheal ≈ 2mm x 2mm (according to the standard operating procedure, SOP, for the AllerGen NCE Clinical Investigator Collaborative, CIC).
https://ift.tt/2QObV2H
Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes
Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on the transcription factor expression and cytokine production patterns in different types of innate lymphoid cells (ILCs), in parallel with those of adaptive CD4+ T helper (Th) cells and CD8+ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging around the immune response deviation into type 1 (orchestrated by ILC1s, Tc1 and Th1 cells), type 2 (characterized by ILC2s, Tc2 and Th2 cells), and type 3 (mediated by ILC3s, Tc17 and Th17 cells) responses.
https://ift.tt/2A7I4gi
Author's Response to Hopp's Commentary
We would thank Dr. Hopp for his interesting correspondence "A New Acronym for PPI-REE"?)1 in response to our summary of the new consensus agreement for the diagnosis of Eosinophilic Esophagitis (EoE)2. One goal of the new guidelines was to simplify the diagnosis and terminology. In addition, the new diagnostic criteria were developed so that patients diagnosed with EoE with previous consensus guidelines would still be considered to have EoE. However, the proposed abbreviation of EoE-PPI-R (Eosinophilic Esophagitis-Proton Pump Inhibitor Responsive) seems to add extra complexity to the terminology.
https://ift.tt/2QR0bwx
Avocado: An Emerging Culprit in Food Protein-Induced Enterocolitis Syndrome?
Food protein-induced enterocolitis syndrome (FPIES) is a poorly understood, immunologically mediated, gastrointestinal food-associated hypersensitivity often presenting in infants and toddlers.1 Incidence data are limited; estimates vary from 1.5 to 30 per 10,000.2,3 Despite being more prevalent than previously thought, diagnostic delay is common4 and clinician awareness of FPIES appears to be low.5 Reactions are typified by profuse vomiting, often accompanied by diarrhea, lethargy, and pallor; and may be progress to severe dehydration, acidosis, and shock.
https://ift.tt/2A7I2Fc
Prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma – A review
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): José Pedro L. Nunes, André C. Cunha, Tiago Meirinhos, Alzira Nunes, Paulo M. Araújo, Ana R. Godinho, Eduardo M. Vilela, Carlos Vaz
Abstract
The prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma patients was reviewed, based on reports cited in two major scientific databases.
Data was collected on the following types of antibodies: antinuclear, anti-double-stranded DNA, anticentromere, anti-CENP-A, anti-CENP-B, anti-bicaudal D2, anti-nucleolar, anti-Scl-70 (anti-topoisomerase I), anti-topoisomerase II α, anti-RNP, anti-U1RNP, anti-U3RNP, anti-RNA polymerase III, anti-Th/To, anti-histone, antiphospholipid, anti-PmScl, anti-Sm, anti SSA (anti-Ro), anti SSB (La), anti-Ro52 (TRIM 21), anti-Ku, anti-B23, anti-RuvBL1, anti-RuvBL2, anti-fibrin bound tissue plasminogen activator, anti-endothelial cell, anti-phosphatidylserine-prothrombin complex, anti-endothelin-1 type A receptor, anti-angiotensin II type 1 receptor, anti‑carbonic anhydrase II, anti-fibroblast, anti-cyclic citrullinated peptide, anti-4-sulfated N-Acetyl-lactosamine, class I and II anti-human leukocyte antigen.
Auto-antibodies were shown by different authors to be associated to this condition, with different prevalence values for each type of auto-antibody. Antinuclear antibodies, anti-centromere antibodies, antiphospholipid antibodies, anti-U3 RNP antibodies and anti-Th/To antibodies would appear to show a particularly important prevalence in scleroderma patients with pulmonary hypertension, appearing in about 8/10 (antinuclear), 1/ 2 (anti-centromere, anti-phospholipid), and 1/4 (anti-U3RNP, anti-Th/To) of patients.
The available evidence points in the direction of a strong association between auto-immune mechanisms and pulmonary hypertension in the setting of scleroderma.
https://ift.tt/2A6C7Ag
HIBISCUS: HYDROXYCHLOROQUINE FOR THE SECONDARY PREVENTION OF THROMBOTIC AND OBSTETRICAL EVENTS IN PRIMARY ANTIPHOSPHOLIPID SYNDROME
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Cristina Belizna, Francesca Pregnolato, Sebastien Abad, Jaume Alijotas-Reig, Howard Amital, Zahir Amoura, Laura Andreoli, Emmanuel Andres, Achile Aouba, Sule Apras Bilgen, Laurent Arnaud, Boris Bienvenu, Viktoria Bitsadze, Patrick Blanco, Miri Blank, Maria Orietta Borghi, Antonia Caligaro, Elisabeta Candrea, Valentina Canti, Laurent Chiche
Abstract
The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS (Cervera et al., 2009, 2015 [2,3]).
Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects (Pericleous et al., 2016; Andrade and Tektonidou, 2016; Belizna, 2015; Erkan et al., 2014; Erkan and Lockshin, 2012; De Carolis et al., 2015; Mekinian et al., 2015; Merashli et al., 2015; Galli, 2014; Lopez-Pedrera et al., 2015; Hu et al., 2017; Ben-Zvi et al., 2012; Belizna et al., 2017 [[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]]).
Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency.
Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial.
This trial consists in two parts: a retrospective and a prospective study.
The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
https://ift.tt/2QMHdqS
Celiac disease and endocrine autoimmunity – the genetic link
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): George J. Kahaly, Lara Frommer, Detlef Schuppan
Abstract
Celiac disease is a small intestinal inflammatory disease with autoimmune features that is triggered and maintained by the ingestion of the storage proteins (gluten) of wheat, barley and rye. The prevalence of celiac disease is increased in patients with monoglandular and/or polyglandular autoimmunity and their relatives. Between 10 and 30% of patients with celiac disease are thyroid and/or type 1 diabetes antibody positive, while around 5 to 7% of patients with autoimmune thyroid disease and/or type 1 diabetes are IgA anti-tissue transglutaminase antibody positive. The close relationship between celiac disease and endocrine autoimmunity is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and/or DQ8 (DQA1*0301-DQB1*0302), that are tightly linked to DR3 and DR4, respectively, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms of various genes that are involved in immune regulation have been identified as "overlap" susceptibility genes for both celiac disease and monoglandular or polyglandular autoimmunity. While plausible, it remains to be established how far a gluten free diet may prevent or ameliorate glandular autoimmunity. In conclusion, all patients with celiac disease should be screened for type 1 diabetes and/or autoimmune thyroid disease. Conversely, patients with the above autoimmune endocrine disorders should be also screened for celiac disease.
https://ift.tt/2A7cwHh
Low-dose tocilizumab for relapsing giant cell arteritis in the elderly, fragile patient: Beyond the GiACTA trial
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Giovanni Maria Rossi, Alessandro Mannoni, Gerardo Di Scala, Elena Silvestri, Rafaela Diana Cojan, Lorenzo Vannozzi, Alessandra Bettiol, Augusto Vaglio, Giacomo Emmi
https://ift.tt/2QMH8Ds
Autoinflammatory/autoimmunity syndrome induced by adjuvants (ASIA; Shoenfeld's syndrome): A new flame
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Jan Willem Cohen Tervaert
Abstract
In the present review, recent findings regarding autoimmune/inflammatory syndrome by adjuvants (ASIA) are described. Patients with ASIA present with complaints such as fatigue, cognitive impairment, arthralgias, myalgias, pyrexia, dry eyes and dry mouth. During the last few years, it has been postulated that these symptoms in patients with foreign body implants are due to a chronic inflammatory process and an adjuvant effect of the implanted biomaterial. Ultimately, these inflammatory reactions result in (an increase of) allergies, autoimmune diseases, immune deficiency and/or lymphomas.
Pre-existent allergic disease has been found to be an important risk factor for the development of ASIA after foreign body implantation. Explantation of the foreign body results in the majority of patients in an amelioration of the symptoms. There is an urgent need to start adequately adjusted epidemiological studies to obtain better evidence which percentage of patients does develop symptoms and/or diseases such as ASIA, immune deficiency, and/or autoimmune diseases after implant surgery.
https://ift.tt/2A6roWs
Anti-neutrophil cytoplasmic antibody-associated chronic inflammatory arthritis without vasculitis. Data from a French nationwide survey
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Guillermo Carvajal Alegria, Matthieu Groh, Dewi Guellec, Eric Toussirot, Julien Rigaud, Martin Soubrier, Sébastien Ottaviani, Guillaume Direz, Alain Saraux, Divi Cornec, CRI (Club Rhumatisme et inflammation)
https://ift.tt/2QJpH6L
with focus on autoimmune liver diseases
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Audrey Beringer, Pierre Miossec
Abstract
The pro-inflammatory cytokine interleukin(IL)-17 and IL-17-producing cells are important players in the pathogenesis of many autoimmune / inflammatory diseases. More recently, they have been associated with liver diseases. This review first describes the general knowledge on IL-17 and IL-17 producing cells. The second part describes the in vitro and in vivo effects of IL-17 on liver cells and the contribution of IL-17 producing cells to liver diseases. IL-17 induces immune cell infiltration and liver damage driving to hepatic inflammation and fibrosis and contributes to autoimmune liver diseases. The circulating levels of IL-17 and the frequency of IL-17-producing cells are elevated in a variety of acute and chronic liver diseases. The last part focuses on the effects of IL-17 deletion or neutralization in various murine models. Some of these observed beneficial effects suggest that targeting the IL-17 axis could be a new therapeutic strategy to prevent chronicity and progression of various liver diseases.
https://ift.tt/2A6sstf
Recent advances in mouse models for systemic sclerosis
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Xiaoyang Yue, Xinhua Yu, Frank Petersen, Gabriela Riemekasten
Abstract
SSc is a complex rheumatoid disease characterized by autoimmunity, fibrosis and vasculopathy. Mouse models provide powerful research tools for exploring the pathogenesis of the human diseases. Each mouse model can represent a specific way leading to the development of disease. Moreover, mouse models can be used to investigate the role of candidate molecule in the pathogenesis of disease. So far, more than twenty mouse models for SSc have been established and provide new insights in the understanding of the pathogenesis of SSc. In this review, we provide an overview on recent advances in the field of experimental SSc. We introduce novel mouse models generated in the recent years and discuss their relevance to the SSc pathogenesis. Moreover, we summarize and discuss recent findings in the pathogenesis of classical SSc mouse models.
https://ift.tt/2QKSXtO
Dimethyl fumarate treatment in multiple sclerosis: Recent advances in clinical and immunological studies
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Gwendoline Montes Diaz, Raymond Hupperts, Judith Fraussen, Veerle Somers
Abstract
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which demyelination and neurodegeneration occurs. The immune system of MS patients is characterized by a dysregulation in the balance between pro- and anti-inflammatory immune cells, whereby both the innate and adaptive immune system are involved. Dimethyl fumarate (DMF) was licensed in 2013 as an oral first-line therapy for relapsing-remitting (RR)MS patients. It has a strong efficacy with neuroprotective and immunomodulatory effects and a favourable benefit-risk profile. However, the effects of DMF on the immune system of MS patients were not clear before entering the market. During the last years, numerous in vitro and ex vivo studies have clarified the working mechanism of DMF in MS. Here, we discuss the pharmacokinetics of DMF and its effect on molecular immune-related pathways, which is further linked to the clinical and immunological effects of DMF treatment. The efficacy and safety of DMF treatment for RRMS is discussed as reported from clinical trials. Further, the immunological effects of DMF treatment in RRMS patients are addressed in more detail, including the distribution and function of immune cells. Taken together, evidence from recent studies points to a multifactorial working mechanism of DMF treatment in MS which leads to a restored immune balance favouring a more tolerogenic or anti-inflammatory immune profile.
https://ift.tt/2A5MnJ0
Giant--cell arteritis--related mortality in France: A multiple--cause--of--death analysis Giant--cell arteritis--related mortality in France
Publication date: Available online 11 October 2018
Source: Autoimmunity Reviews
Author(s): Thibaud Chazal, Raphael Lhote, Grégoire Rey, Julien Haroche, Mireille Eb, Zahir Amoura, Fleur Cohen Aubart
Abstract
Objectives: Giant--cell arteritis (GCA) is a large vessel vasculitis. Data regarding mortality are controversial. We describe the mortality data of the French death certificates for the period of 2005 to 2014.
Methods: Using multiple--cause--of--death (MCOD) analysis, we calculated age--adjusted mortality rates for GCA, examined differences in mortality rates according to age and gender and analyzed the underlying causes of death (UCD).
Results
We analyzed 4628 death certificates listing a diagnosis of GCA as UCD or non-underlying cause of death (NUCD). The mean age of death was 86 (±6.8) years. The overall age--standardized mortality rate among GCA patients was 7.2 per million population. Throughout the study period, the mean age of death was significantly increased (r = 0.17, p < .0001) in both genders. There was no significant difference with age repartition of death in the general population (p = .26). When GCA was listed as the UCD, most frequent associated diseases were cardiovascular (79%) and infectious diseases (35%). When GCA was reported as the NUCD, the listed UCD was a cardiovascular event in 40% of cases, neoplasm in 13%, neurodegenerative disorder in 11% and infectious disease in 10%. When GCA was the UCD or NUCD, an age--adjusted observed/expected ratio > 1 in GCA--associated mortality compared with the general population mortality was observed for tuberculosis, pneumonia and cardiovascular diseases.
Conclusion: In this analysis of French death certificates mentioning GCA, we observed a.
stable standardized mortality rate between 2005 and 2014. The most frequent associated diseases were cardiovascular diseases and infections.
https://ift.tt/2QRKa9J
What speech can tell us: A systematic review of dysarthria characteristics in Multiple Sclerosis
Publication date: Available online 11 October 2018
Source: Autoimmunity Reviews
Author(s): Gustavo Noffs, Thushara Perera, Scott Camaron Kolbe, Camille Jessica Shanahan, Frederique Maria Christina Boonstra, Andrew Evans, Helmut Butzkueven, Anneke van der Walt, Adam Phillip Vogel
Abstract
IMPORTANCE: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression.
OBSERVATIONS: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis.
CONCLUSION AND RELEVANCE: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials.
https://ift.tt/2A6BcQn
Polymerase-1 pathway activation in acute multiple sclerosis relapse
Publication date: Available online 11 October 2018
Source: Autoimmunity Reviews
Author(s): Anat Achiron, Rina Falb, Anna Feldman, Maria Bovim, Onn Rosenblum, Ida Sarova Pinhas, David Magalashvili, Mark Dolev, Shay Menascu, Michael Gurevich
Abstract
Background
The operating molecular mechanisms that characterize a multiple sclerosis (MS) relapse has not been thoroughly studied. We have shown that increased expression of RNA polymerase 1 (POL1) molecular pathway is associated with increased MS disease activity.
Objective
To assess POL1 pathway expression during acute MS relapse.
Methods
We studied POL1 pathway activation and associated biomarkers during the first acute optic neuritis attack of MS, and in relapsing-remitting MS patients treated with disease-modifying drugs (DMDs) experiencing an acute MS relapse or a radiological relapse using gene expression microarrays and quantitative RT-PCR.
Results
In MS patients (N = 6) during the first acute optic neuritis attack POL1 pathway activation was evident by over-expression of POL1 related network including transcription factor UBTF and downstream components of Assembly of RNA POL1 complex (1.92E-03). POL1 related biomarkers RRN3, POLR1D and LRPPRC were over-expressed x1.6 (p = .002), ×1.7 (p = .01) and x2.0 (p = .001) times higher respectively, in MS patients (N = 30) during acute clinical relapse as compared with remission. Similarly, in MS patients (N = 21) that presented with a radiological relapse, we observed significant activation of POL1 related biomarkers including RRN3 (p = .01), POLR1D (p = .002), POLR1E (p = .0001) and LRPPRC (p = .006), as compared with remission, as well as overexpression of a large group of genes encoding ribosomal proteins like RPS6KA3 (p = 7.2E-6), RRP8 (p = .0002) and RPCS9 (p = .0008).
Conclusions
Our findings suggest that targeted inactivation of Pol-1 pathway may represent a novel strategy for a better treatment of acute MS relapse.
https://ift.tt/2A63335
Prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma – A review
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): José Pedro L. Nunes, André C. Cunha, Tiago Meirinhos, Alzira Nunes, Paulo M. Araújo, Ana R. Godinho, Eduardo M. Vilela, Carlos Vaz
Abstract
The prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma patients was reviewed, based on reports cited in two major scientific databases.
Data was collected on the following types of antibodies: antinuclear, anti-double-stranded DNA, anticentromere, anti-CENP-A, anti-CENP-B, anti-bicaudal D2, anti-nucleolar, anti-Scl-70 (anti-topoisomerase I), anti-topoisomerase II α, anti-RNP, anti-U1RNP, anti-U3RNP, anti-RNA polymerase III, anti-Th/To, anti-histone, antiphospholipid, anti-PmScl, anti-Sm, anti SSA (anti-Ro), anti SSB (La), anti-Ro52 (TRIM 21), anti-Ku, anti-B23, anti-RuvBL1, anti-RuvBL2, anti-fibrin bound tissue plasminogen activator, anti-endothelial cell, anti-phosphatidylserine-prothrombin complex, anti-endothelin-1 type A receptor, anti-angiotensin II type 1 receptor, anti‑carbonic anhydrase II, anti-fibroblast, anti-cyclic citrullinated peptide, anti-4-sulfated N-Acetyl-lactosamine, class I and II anti-human leukocyte antigen.
Auto-antibodies were shown by different authors to be associated to this condition, with different prevalence values for each type of auto-antibody. Antinuclear antibodies, anti-centromere antibodies, antiphospholipid antibodies, anti-U3 RNP antibodies and anti-Th/To antibodies would appear to show a particularly important prevalence in scleroderma patients with pulmonary hypertension, appearing in about 8/10 (antinuclear), 1/ 2 (anti-centromere, anti-phospholipid), and 1/4 (anti-U3RNP, anti-Th/To) of patients.
The available evidence points in the direction of a strong association between auto-immune mechanisms and pulmonary hypertension in the setting of scleroderma.
https://ift.tt/2A6C7Ag
HIBISCUS: HYDROXYCHLOROQUINE FOR THE SECONDARY PREVENTION OF THROMBOTIC AND OBSTETRICAL EVENTS IN PRIMARY ANTIPHOSPHOLIPID SYNDROME
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Cristina Belizna, Francesca Pregnolato, Sebastien Abad, Jaume Alijotas-Reig, Howard Amital, Zahir Amoura, Laura Andreoli, Emmanuel Andres, Achile Aouba, Sule Apras Bilgen, Laurent Arnaud, Boris Bienvenu, Viktoria Bitsadze, Patrick Blanco, Miri Blank, Maria Orietta Borghi, Antonia Caligaro, Elisabeta Candrea, Valentina Canti, Laurent Chiche
Abstract
The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS (Cervera et al., 2009, 2015 [2,3]).
Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects (Pericleous et al., 2016; Andrade and Tektonidou, 2016; Belizna, 2015; Erkan et al., 2014; Erkan and Lockshin, 2012; De Carolis et al., 2015; Mekinian et al., 2015; Merashli et al., 2015; Galli, 2014; Lopez-Pedrera et al., 2015; Hu et al., 2017; Ben-Zvi et al., 2012; Belizna et al., 2017 [[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]]).
Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency.
Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial.
This trial consists in two parts: a retrospective and a prospective study.
The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
https://ift.tt/2QMHdqS
Celiac disease and endocrine autoimmunity – the genetic link
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): George J. Kahaly, Lara Frommer, Detlef Schuppan
Abstract
Celiac disease is a small intestinal inflammatory disease with autoimmune features that is triggered and maintained by the ingestion of the storage proteins (gluten) of wheat, barley and rye. The prevalence of celiac disease is increased in patients with monoglandular and/or polyglandular autoimmunity and their relatives. Between 10 and 30% of patients with celiac disease are thyroid and/or type 1 diabetes antibody positive, while around 5 to 7% of patients with autoimmune thyroid disease and/or type 1 diabetes are IgA anti-tissue transglutaminase antibody positive. The close relationship between celiac disease and endocrine autoimmunity is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and/or DQ8 (DQA1*0301-DQB1*0302), that are tightly linked to DR3 and DR4, respectively, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms of various genes that are involved in immune regulation have been identified as "overlap" susceptibility genes for both celiac disease and monoglandular or polyglandular autoimmunity. While plausible, it remains to be established how far a gluten free diet may prevent or ameliorate glandular autoimmunity. In conclusion, all patients with celiac disease should be screened for type 1 diabetes and/or autoimmune thyroid disease. Conversely, patients with the above autoimmune endocrine disorders should be also screened for celiac disease.
https://ift.tt/2A7cwHh
Low-dose tocilizumab for relapsing giant cell arteritis in the elderly, fragile patient: Beyond the GiACTA trial
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Giovanni Maria Rossi, Alessandro Mannoni, Gerardo Di Scala, Elena Silvestri, Rafaela Diana Cojan, Lorenzo Vannozzi, Alessandra Bettiol, Augusto Vaglio, Giacomo Emmi
https://ift.tt/2QMH8Ds
Autoinflammatory/autoimmunity syndrome induced by adjuvants (ASIA; Shoenfeld's syndrome): A new flame
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Jan Willem Cohen Tervaert
Abstract
In the present review, recent findings regarding autoimmune/inflammatory syndrome by adjuvants (ASIA) are described. Patients with ASIA present with complaints such as fatigue, cognitive impairment, arthralgias, myalgias, pyrexia, dry eyes and dry mouth. During the last few years, it has been postulated that these symptoms in patients with foreign body implants are due to a chronic inflammatory process and an adjuvant effect of the implanted biomaterial. Ultimately, these inflammatory reactions result in (an increase of) allergies, autoimmune diseases, immune deficiency and/or lymphomas.
Pre-existent allergic disease has been found to be an important risk factor for the development of ASIA after foreign body implantation. Explantation of the foreign body results in the majority of patients in an amelioration of the symptoms. There is an urgent need to start adequately adjusted epidemiological studies to obtain better evidence which percentage of patients does develop symptoms and/or diseases such as ASIA, immune deficiency, and/or autoimmune diseases after implant surgery.
https://ift.tt/2A6roWs
Anti-neutrophil cytoplasmic antibody-associated chronic inflammatory arthritis without vasculitis. Data from a French nationwide survey
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Guillermo Carvajal Alegria, Matthieu Groh, Dewi Guellec, Eric Toussirot, Julien Rigaud, Martin Soubrier, Sébastien Ottaviani, Guillaume Direz, Alain Saraux, Divi Cornec, CRI (Club Rhumatisme et inflammation)
https://ift.tt/2QJpH6L
with focus on autoimmune liver diseases
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Audrey Beringer, Pierre Miossec
Abstract
The pro-inflammatory cytokine interleukin(IL)-17 and IL-17-producing cells are important players in the pathogenesis of many autoimmune / inflammatory diseases. More recently, they have been associated with liver diseases. This review first describes the general knowledge on IL-17 and IL-17 producing cells. The second part describes the in vitro and in vivo effects of IL-17 on liver cells and the contribution of IL-17 producing cells to liver diseases. IL-17 induces immune cell infiltration and liver damage driving to hepatic inflammation and fibrosis and contributes to autoimmune liver diseases. The circulating levels of IL-17 and the frequency of IL-17-producing cells are elevated in a variety of acute and chronic liver diseases. The last part focuses on the effects of IL-17 deletion or neutralization in various murine models. Some of these observed beneficial effects suggest that targeting the IL-17 axis could be a new therapeutic strategy to prevent chronicity and progression of various liver diseases.
https://ift.tt/2A6sstf
Recent advances in mouse models for systemic sclerosis
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Xiaoyang Yue, Xinhua Yu, Frank Petersen, Gabriela Riemekasten
Abstract
SSc is a complex rheumatoid disease characterized by autoimmunity, fibrosis and vasculopathy. Mouse models provide powerful research tools for exploring the pathogenesis of the human diseases. Each mouse model can represent a specific way leading to the development of disease. Moreover, mouse models can be used to investigate the role of candidate molecule in the pathogenesis of disease. So far, more than twenty mouse models for SSc have been established and provide new insights in the understanding of the pathogenesis of SSc. In this review, we provide an overview on recent advances in the field of experimental SSc. We introduce novel mouse models generated in the recent years and discuss their relevance to the SSc pathogenesis. Moreover, we summarize and discuss recent findings in the pathogenesis of classical SSc mouse models.
https://ift.tt/2QKSXtO
Dimethyl fumarate treatment in multiple sclerosis: Recent advances in clinical and immunological studies
Publication date: Available online 12 October 2018
Source: Autoimmunity Reviews
Author(s): Gwendoline Montes Diaz, Raymond Hupperts, Judith Fraussen, Veerle Somers
Abstract
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which demyelination and neurodegeneration occurs. The immune system of MS patients is characterized by a dysregulation in the balance between pro- and anti-inflammatory immune cells, whereby both the innate and adaptive immune system are involved. Dimethyl fumarate (DMF) was licensed in 2013 as an oral first-line therapy for relapsing-remitting (RR)MS patients. It has a strong efficacy with neuroprotective and immunomodulatory effects and a favourable benefit-risk profile. However, the effects of DMF on the immune system of MS patients were not clear before entering the market. During the last years, numerous in vitro and ex vivo studies have clarified the working mechanism of DMF in MS. Here, we discuss the pharmacokinetics of DMF and its effect on molecular immune-related pathways, which is further linked to the clinical and immunological effects of DMF treatment. The efficacy and safety of DMF treatment for RRMS is discussed as reported from clinical trials. Further, the immunological effects of DMF treatment in RRMS patients are addressed in more detail, including the distribution and function of immune cells. Taken together, evidence from recent studies points to a multifactorial working mechanism of DMF treatment in MS which leads to a restored immune balance favouring a more tolerogenic or anti-inflammatory immune profile.
https://ift.tt/2A5MnJ0
Giant--cell arteritis--related mortality in France: A multiple--cause--of--death analysis Giant--cell arteritis--related mortality in France
Publication date: Available online 11 October 2018
Source: Autoimmunity Reviews
Author(s): Thibaud Chazal, Raphael Lhote, Grégoire Rey, Julien Haroche, Mireille Eb, Zahir Amoura, Fleur Cohen Aubart
Abstract
Objectives: Giant--cell arteritis (GCA) is a large vessel vasculitis. Data regarding mortality are controversial. We describe the mortality data of the French death certificates for the period of 2005 to 2014.
Methods: Using multiple--cause--of--death (MCOD) analysis, we calculated age--adjusted mortality rates for GCA, examined differences in mortality rates according to age and gender and analyzed the underlying causes of death (UCD).
Results
We analyzed 4628 death certificates listing a diagnosis of GCA as UCD or non-underlying cause of death (NUCD). The mean age of death was 86 (±6.8) years. The overall age--standardized mortality rate among GCA patients was 7.2 per million population. Throughout the study period, the mean age of death was significantly increased (r = 0.17, p < .0001) in both genders. There was no significant difference with age repartition of death in the general population (p = .26). When GCA was listed as the UCD, most frequent associated diseases were cardiovascular (79%) and infectious diseases (35%). When GCA was reported as the NUCD, the listed UCD was a cardiovascular event in 40% of cases, neoplasm in 13%, neurodegenerative disorder in 11% and infectious disease in 10%. When GCA was the UCD or NUCD, an age--adjusted observed/expected ratio > 1 in GCA--associated mortality compared with the general population mortality was observed for tuberculosis, pneumonia and cardiovascular diseases.
Conclusion: In this analysis of French death certificates mentioning GCA, we observed a.
stable standardized mortality rate between 2005 and 2014. The most frequent associated diseases were cardiovascular diseases and infections.
https://ift.tt/2QRKa9J
What speech can tell us: A systematic review of dysarthria characteristics in Multiple Sclerosis
Publication date: Available online 11 October 2018
Source: Autoimmunity Reviews
Author(s): Gustavo Noffs, Thushara Perera, Scott Camaron Kolbe, Camille Jessica Shanahan, Frederique Maria Christina Boonstra, Andrew Evans, Helmut Butzkueven, Anneke van der Walt, Adam Phillip Vogel
Abstract
IMPORTANCE: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression.
OBSERVATIONS: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis.
CONCLUSION AND RELEVANCE: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials.
https://ift.tt/2A6BcQn
Polymerase-1 pathway activation in acute multiple sclerosis relapse
Publication date: Available online 11 October 2018
Source: Autoimmunity Reviews
Author(s): Anat Achiron, Rina Falb, Anna Feldman, Maria Bovim, Onn Rosenblum, Ida Sarova Pinhas, David Magalashvili, Mark Dolev, Shay Menascu, Michael Gurevich
Abstract
Background
The operating molecular mechanisms that characterize a multiple sclerosis (MS) relapse has not been thoroughly studied. We have shown that increased expression of RNA polymerase 1 (POL1) molecular pathway is associated with increased MS disease activity.
Objective
To assess POL1 pathway expression during acute MS relapse.
Methods
We studied POL1 pathway activation and associated biomarkers during the first acute optic neuritis attack of MS, and in relapsing-remitting MS patients treated with disease-modifying drugs (DMDs) experiencing an acute MS relapse or a radiological relapse using gene expression microarrays and quantitative RT-PCR.
Results
In MS patients (N = 6) during the first acute optic neuritis attack POL1 pathway activation was evident by over-expression of POL1 related network including transcription factor UBTF and downstream components of Assembly of RNA POL1 complex (1.92E-03). POL1 related biomarkers RRN3, POLR1D and LRPPRC were over-expressed x1.6 (p = .002), ×1.7 (p = .01) and x2.0 (p = .001) times higher respectively, in MS patients (N = 30) during acute clinical relapse as compared with remission. Similarly, in MS patients (N = 21) that presented with a radiological relapse, we observed significant activation of POL1 related biomarkers including RRN3 (p = .01), POLR1D (p = .002), POLR1E (p = .0001) and LRPPRC (p = .006), as compared with remission, as well as overexpression of a large group of genes encoding ribosomal proteins like RPS6KA3 (p = 7.2E-6), RRP8 (p = .0002) and RPCS9 (p = .0008).
Conclusions
Our findings suggest that targeted inactivation of Pol-1 pathway may represent a novel strategy for a better treatment of acute MS relapse.
https://ift.tt/2A63335
Parental anxiety towards ‘refer’ results in Newborn Hearing Screening (NHS) in South India: A hospital based study
Publication date: Available online 13 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Vijaya Kumar Beaula Vincy, Jayashree Seethapathy, Prakash Boominathan
https://ift.tt/2OYuUdM
The Diagnostic Role of Triple Endoscopy in Pediatric Patients with Chronic Cough
Publication date: Available online 13 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): M. Shannon Fracchia, Gillian Diercks, Anna Cook, Cheryl Hersh, Stephen Hardy, Marina Hartnick, Christopher Hartnick
https://ift.tt/2OYUW0i
Management of Velopharyngeal Dysfunction in Patients with 22q11.2 Deletion Syndrome: A Survey of Practice Patterns
Publication date: Available online 12 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Oksana A. Jackson, Kaitlyn Paine, Leanne Magee, Meg Ann Maguire, Elaine Zackai, Donna M. McDonald-McGinn, Susan McCormack, Cynthia Solot
Abstract
Objective
To determine demographics and practice patterns of surgeons treating velopharyngeal dysfunction (VPD) in patients with 22q11.2 deletion syndrome (22q11.2DS).
Methods
An anonymous electronic survey study was administered to the surgical membership of the American Cleft Palate-Craniofacial Association and the Society for Ear Nose and Throat Advances in Children. The survey queried surgeon demographics and differences in management practices for submucous cleft palate (SMCP), pharyngoplasty algorithms, and self-reported complications for nonsyndromic versus 22q11.2DS patients.
Results
126 surveys were returned from 9 international regions with the majority from the United States (73%), followed by Western Europe (9.5%) and Canada (7.9%). Plastic surgery was the most common specialty (61.9%), followed by otolaryngology (27.8%). 88.1% reported fellowship training, and 33% completed multiple fellowships. Prior to proceeding with pharyngoplasty in 22q11.2DS patients, surgeons required the following assessments: speech evaluation (79.4%), velopharyngeal imaging (51.6%), cardiac evaluation (50.0%), carotid artery MRI (29.4%), and cervical spine x-rays (11.1%). Nasoendoscopy was the most common modality used for imaging the velopharynx. Overall, providers managed patients with 22q11.2DS similarly to nonsyndromic patients, with several significant exceptions including that they were more likely to perform SMCP repair alone as a first approach in nonsyndromic patients (p=0.031) and posterior pharyngeal flap without SMCP repair in those with 22q11.2DS (p=0.017).
Conclusions
Practice patterns for the management of VPD in patients with 22q11.2DS vary across providers. Further collaborative studies are needed to develop optimal treatment paradigms for VPD in patients with 22q11.2 DS.
https://ift.tt/2Px2AMy
Speech development in young children with Mondini dysplasia who had undergone cochlear implantation
Publication date: Available online 12 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Shuang Qi, Ying Kong, Tianqiu Xu, Ruijuan Dong, Jing Lv, Xianlei Wang, Beier Qi, Shuo Wang, Fei Yan, Yongxin Li, Lihui Huang, Xueqing Chen
Abstract
Objective
The purpose of this study was to investigate the development of speech skills in young children with Mondini dysplasia and age-matched deaf children with radiologically normal inner ears over a period of 5 years after cochlear implantation (CI).
Methods
In total, 700 congenitally severely to profoundly deaf children (281 girls and 419 boys) participated in this study. All of the participants had undergone unilateral CI surgery before 36 months of age. The participants were categorized into two groups based on the absence or presence of Mondini dysplasia in the implanted ear, as assessed via high-resolution, thin-slice computerized tomography or magnetic resonance imaging: group A comprised 592 children with radiologically normal inner ears and group B comprised 108 children with Mondini dysplasia. The Meaningful Use of Speech Scale (MUSS) and Speech Intelligibility Rating (SIR) were used to evaluate the speech performance of all young children at various time points: pre-surgery and at 1, 3, 6, 12, 24, 36, 48, and 60 months after switch-on programming.
Results
The mean scores of SIR and MUSS in children from both group A and group B showed significant improvements over time. No significant differences were found in the mean scores of SIR between the two groups at any time interval during the 5-year follow-up. The mean score of MUSS was significantly different between group A and group B at 12, 24, and 36 months after implantation, whereas no obvious differences were noted pre-surgery, and at 1, 3, 6, 48, and 60 months post-operation.
Conclusions
Young children with Mondini dysplasia develop their speech skills at a fast rate and achieve similar speech acquisition compared to age-matched children with radiologically normal inner ears 5 years post-operation. Therefore, CI is an effective intervention method for young children with Mondini dysplasia.
https://ift.tt/2Px2Aw2
The wheel-shaped composite cartilage graft (WsCCG) and temporalis fascia for type 1 tympanoplasty: a prospective, randomized study
Abstract
Objectives
To compare the anatomical and functional outcomes of two different grafts which are used for the reconstruction of subtotal or total tympanic membrane perforations: the wheel-shaped composite cartilage graft (WsCCG) and temporalis fascia (TF).
Methods
Ninety patients (94 ears) who underwent type 1 tympanoplasty for non-complicated chronic otitis media between March 2014 and June 2016 in a tertiary referral center were included in a randomized, controlled, prospective clinical trial. Tympanic membranes were reconstructed with the WsCCG or TF.
Results
Outcomes of 91 surgeries performed on 87 adults (> 18 years of age) were evaluated in the study. Forty-three patients (44 ears) were included in the WsCCG group; 44 patients (47 ears) were included in the TF group. The mean post-operative follow-up was 14.9 months for the WsCCG group and 15.1 months for the TF group. There was no statistically significant difference in post-operative pure tone average (PTA) (p = 0.19), air-bone gap (ABG) (p = 0.64), PTA gain (p = 0.82) and ABG closure (p = 0.89) values between two groups. Graft success rates at 6 months after surgery were 82.9% (39/47) and 97.7% (43/44) for TF and WsCCG, respectively. At the first year, success rates were 85.1% (40/47) for TF and 97.7% (43/44) for WsCCG. A statistically significant difference was observed in graft success rates between two groups (p = 0.039).
Conclusions
Both TF and WsCCG lead to satisfactory functional results, but the WsCCG clearly leads to superior anatomical outcomes with a graft success rate of 97.7%. The WsCCG is a suitable graft for subtotal or total tympanic membrane perforations and has the advantages of being a one-piece, flexible, composite, and physically resistant graft.
https://ift.tt/2OUTv32
The aging effect on upper airways collapse of patients with obstructive sleep apnea syndrome
Abstract
Purpose
To evaluate, using drug-induced sleep endoscopy (DISE), sites of upper airway obstruction and pattern of collapse in patients over 65 years old affected by obstructive sleep apnea. To compare sites and pattern of collapse of elderly patients with a group of patients younger than 65 years.
Methods
A group of 55 patients aged over 65 years were enrolled in this prospective study. Fifty patients under 65 years old were collected in the control group. Polysomnographic data and clinical parameters such as the daytime sleepiness, and body mass index were evaluated for both groups of patients. All patients underwent DISE examination with VOTE classification.
Results
The AHI value increased with aging whereas elderly patients presented a reduction in daytime sleepiness. Elderly patients showed a higher incidence of total collapse in the velum region compared to younger patients (90.9% vs 70%;); the older patients showed a lower degree of total oropharyngeal lateral wall collapse with respect to younger patients, (20% vs 50%). No difference in tongue base collapse emerged between the two subgroups of patients.
Conclusion
Elderly patients showed a higher incidence of total collapse in the velum and a lower incidence in the oropharyngeal lateral wall compared to younger patients.
https://ift.tt/2CfL4c0
Outcomes after up-front surgery and metronomic neoadjuvant chemotherapy with S-1 or UFT for early tongue squamous cell carcinoma
Abstract
Background
Our aim was to investigate the disease-free survival in patients with tongue squamous cell carcinoma receiving metronomic neoadjuvant chemotherapy with 5-fluorouracil prodrugs (UFT or S-1) plus bleomycin compared with those who had up-front surgery retrospectively.
Methods
In this retrospective study, 108 patients with stages I to II tongue squamous cell carcinoma who had undergone surgery were divided into the "surgery group" or "neoadjuvant chemotherapy group."
Results
A total of 41 patients received up-front surgery; 67 received metronomic neoadjuvant chemotherapy with UFT plus bleomycin (39) or S-1 plus bleomycin (28). The rate of disease-free survival was the primary outcome measure. Neoadjuvant 5-fluorouracil prodrugs did not correlate higher with improved disease-free survival than up-front surgery (72 and 54%, respectively; hazard ratio for recurrence or death, 0.54; 95% confidence interval [CI], 0.28 to 1.03; P = 0.06). Patients who received S-1 were more likely than those who received UFT to have pathological complete response (46% vs. 15%; P = 0.007). Neoadjuvant S-1 significantly improved disease-free survival as compared with up-front surgery (79% vs. 54%; hazard ratio, 0.41; 95% CI, 0.15 to 0.98; P = 0.04). However, neoadjuvant UFT did not improve disease-free survival as compared with up-front surgery (67% vs. 54%, respectively; hazard ratio, 0.66; 95% CI, 0.31 to 1.33; P = 0.24).
Conclusions
Neoadjuvant S-1 chemotherapy, as compared with up-front surgery, significantly improved disease-free survival among patients with tongue squamous cell carcinoma.
Clinical relevance
A choice of drugs before neoadjuvant metronomic chemotherapy is needed.
https://ift.tt/2pRU53B
Usefulness of dermoscopy/dermatoscopy to improve the clinical and histopathologic diagnosis of skin cancers
Publication date: Available online 13 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Oriol Yélamos, Ralph P. Braun, Konstantinos Liopyris, Zachary J. Wolner, Katrin Kerl, Pedram Gerami, Ashfaq A. Marghoob
Abstract
Multiple studies have shown that dermoscopy increases the sensitivity and specificity for the detection of skin cancers compared to naked-eye examination. Dermoscopy can also lead to the detection of thinner and smaller cancers. Furthermore, dermoscopy leads to more precise selection of lesions requiring excision. In essence, dermoscopy helps clinicians differentiate benign from malignant lesions through the presence or absence of specific dermoscopic structures. Therefore, since most dermoscopic structures have direct histopathologic correlates, dermoscopy can allow the prediction of certain histologic findings present in skin cancers, thus helping select management and treatment options for select types of skin cancers. Visualizing dermoscopic structures in the ex vivo specimens can also be beneficial. It can improve the histologic diagnostic accuracy by targeted step-sectioning in areas of concern, which can be marked by the clinician before sending the specimen to the pathologist, or by the pathologist on the excised specimen in the laboratory. In addition, ex vivo dermoscopy can also be used to select tumor areas with genetic importance since some dermoscopic structures have been related to mutations with theragnostic relevance. In the second article of this continuing medical education series we review the impact of dermoscopy on the diagnostic accuracy of skin cancer, how can dermoscopy affect the histopathologic examination, and which dermoscopic features may be more relevant in terms of histological and genetic prediction.
https://ift.tt/2A8mmsw
Dermoscopy/dermatoscopy and dermatopathology correlates of cutaneous neoplasms
Publication date: Available online 13 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Oriol Yélamos, Ralph P. Braun, Konstantinos Liopyris, Zachary J. Wolner, Katrin Kerl, Pedram Gerami, Ashfaq A. Marghoob
Abstract
Dermoscopy is increasingly used by clinicians (dermatologists, family physicians, podiatrists, doctors of osteopathic medicine, etc.) to inform clinical management decisions. Dermoscopic findings and/or images provided to pathologists offer an important insight into the clinician's diagnostic and management thought process. However, with limited dermoscopic training in dermatopathology, dermoscopic descriptions and images provided in the requisition form will provide little value to pathologists. Since most dermoscopic structures have direct histopathological correlates, dermoscopy can act as an excellent communication bridge between the clinician and the pathologist. In the first article of this continuing medical education series we review dermoscopic features and their histopathologic correlates.
https://ift.tt/2QOgqKz
Distinct topological properties of cue-evoked attention processing network in persisters and remitters of childhood ADHD
Publication date: Available online 13 October 2018
Source: Cortex
Author(s): Yuyang Luo, Kurt P. Schulz, Tara L. Alvarez, Jeffrey M. Halperin, Xiaobo Li
Abstract
Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder that persists into adulthood in a sizeable portion of afflicted children. The persistence of ADHD elevates the risk for adverse outcomes that result in substantial individual and societal burden. The objective of this study is to assess neurobiological substrates associated with variability of clinical outcomes in childhood ADHD, which has considerable value for the development of novel interventions that target mechanisms associated with recovery. A total of 36 young adults who were diagnosed with ADHD combined-type during childhood and 33 group-matched controls were involved in the study. Adults with childhood ADHD were further divided into 17 persisters and 19 remitters based on DSM-5 criteria. Functional magnetic resonance imaging data during a cue-evoked attention task were collected from each subject. The cue-evoked attention processing network was constructed using graph theoretic techniques. Network properties, including global-, local-, and nodal-efficiency, and network hubs were computed. Group comparisons of the network properties were conducted. Significantly lower nodal efficiency in right inferior frontal gyrus and reduced left side frontal-parietal functional interactions were observed in both remitters and persisters relative to the controls. The ADHD persisters showed a unique pattern of significantly lower nodal efficiency in right middle frontal gyrus (MFG) and hyper-interactions between bilateral MFG. This study suggests that right MFG functional impairments may relate to inactive fronto-parietal functional interactions for sensory and cognitive information processing and symptom persistence in young adults with childhood ADHD.
https://ift.tt/2yEVkH1
Fiber orientation distribution function from non-negative sparse recovery with quantitative analysis of local fiber orientations and tractography using DW-MRI datasets
Publication date: Available online 13 October 2018
Source: Magnetic Resonance Imaging
Author(s): Thinhinane Megherbi, Gabriel Girard, Aurobrata Ghosh, Fatima Oulebsir-Boumghar, Rachid Deriche
Abstract
Diffusion weighted MRI (DW-MRI) is the unique non-invasive imaging modality capable of estimating in vivo the structure of the white matter. In this paper, we propose, evaluate and validate a new DW-MRI method to model and recover high quality tractogram even with multiple fiber populations in a voxel and from a limited number of acquisitions.
Our method relies on the estimation of the Fiber Orientation Distribution (FOD) function, parameterized as a non-negative sum of rank-1 tensors and the use of a non-negative sparse recovery scheme to efficiently recover the tensors, and their number. Each fiber population of a voxel is characterized by the orientation and the weight of a rank-1 tensor.
Using both deterministic and probabilistic tractography algorithms, we show that our method is able to accurately reconstruct narrow crossing fibers and obtain a high quality connectivity reconstruction even from a limited number of acquisitions. To this end, a validation scheme based on the connectivity recovered from tractography is developed to quantitatively evaluate and analyze the performance of our method. The tractometer tool is used to quantify the tractography obtained from a simulated DW-MRI dataset including a high angular resolution dataset of 60 gradient directions and a dataset of 30 gradient directions, each of them corrupted with Rician noise of SNR 10 and 20. The performance of our FOD model and its impact on the tractography results are also demonstrated and illustrated on in vivo DW-MRI datasets with high and low angular resolutions.
https://ift.tt/2pYQlgN
Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements
Publication date: Available online 13 October 2018
Source: Magnetic Resonance Imaging
Author(s): Sean K. Sethi, Shawn J. Kisch, Kiarash Ghassaban, Ali Rajput, Alex Rajput, Paul S. Babyn, Saifeng Liu, Peter Szkup, E. Mark Haacke
Abstract
Background
Elevated brain iron has been observed in Idiopathic Parkinson's disease (IPD) within the deep gray matter. Using quantitative susceptibility mapping (QSM) and a thresholded high-iron region, we quantified iron content in the midbrain of patients with Parkinson's disease as a function of age.
Methods
We used MRI to scan 24 IPD patients at 3-Tesla. Susceptibility-weighted images were collected with the following parameters, TE: 6 and 20 ms, TR: 30 ms, FA: 15°, and resolution: 0.5 × 0.5 × 2.0 mm3. QSM images were reconstructed from the source phase images. Whole-region and thresholded high-iron (RII) region boundaries for the Substantia Nigra (SN) and Red Nucleus (RN) were traced. Iron content was measured via mean susceptibilities and volumes, which were compared between the groups, as well as between right and left side of the structures within groups.
Results
Twenty patients with mild to moderate IPD were used in this study. For the SN, mean RII iron and volumes were higher in IPD compared to HC, while no differences were seen between the groups when considering whole regions for the left SN, and bilaterally for the RN.
Conclusion
Using a two-region of interest analysis on QSM, we showed that abnormal iron occurs in IPD patients in the SN and with greater volumes compared to HC. This may have application as a biomarker for disease diagnosis and early intervention.
https://ift.tt/2NHHppc
Split Bregman method based level set formulations for segmentation and correction with application to MR images and color images
Publication date: Available online 13 October 2018
Source: Magnetic Resonance Imaging
Author(s): Yunyun Yang, Dongcai Tian, Wenjing Jia, Xiu Shu, Boying Wu
Abstract
At present, magnetic resonance (MR) images have gradually become a major aid for clinical medicine, which has greatly improved the doctor's diagnosis rate. Accurate and fast segmentation of MR images plays an extremely important role in medical research. However, due to the influence of external factors and the defects of imaging devices, the MR images have severe intensity inhomogeneity, which poses a great challenge to accurately segment MR images. To deal with this problem, this paper presents an improved active contour model by combining the level set evolution model (LSE) and the split Bregman method, and gives the two-phase, the multi-phase and the vector-valued formulations of our model, respectively. The use of the split Bregman method accelerates the minimization process of our model by reducing the computation time and iterative times. A slowly varying bias field is added into the energy functional, which is the key to correct inhomogeneous images. By estimating the bias fields, not only can we get accurate image segmentation results, but also a homogeneous image after correction is provided. Then we apply our model to segment a large amount of synthetic and real MR images, including gray and color images. Experimental results shows that our model can provide satisfactory segmentation and correction results for both gray and color images. Besides, compared with the LSE model, our model has higher accuracy and is superior to the LSE model. In addition, experimental results also demonstrate that our model has the advantages of being insensitive to initial contours and robust to noises.
https://ift.tt/2pQ8lcX
NMR diffusometry with guest molecules in nanoporous materials
Publication date: Available online 12 October 2018
Source: Magnetic Resonance Imaging
Author(s): Seungtaik Hwang, Jörg Kärger
Abstract
Application of pulsed field gradient (PFG) NMR to studying molecular diffusion in beds of nanoporous materials has given rise to novel insights and paradigm shifts in our understanding, which are reviewed in the present contribution. This gain in information is, in particular, related to the ability of PFG NMR to discriminate between various mechanisms affecting mass transfer in such systems. Examples include, inter alia, the sensitivity of PFG NMR toward transport enhancement in pore hierarchies as well as toward transport resistances acting, in addition to the diffusional resistance of the genuine pore space, either on the crystal surfaces or in their interior.
https://ift.tt/2NEQI9F
Mucosal Bromodomain-Containing Protein 4 (BRD4) Mediates Aeroallergen-induced Inflammation and Remodeling
Publication date: Available online 13 October 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Bing Tian, Koa Hosoki, Zhiqing Liu, Jun Yang, Yingxin Zhao, Hong Sun, Jia Zhou, Erik Rytting, Lata Kaphalia, William J. Calhoun, Sanjiv Sur, Allan R. Brasier
Abstract
Background
Frequent exacerbations of allergic asthma leads to airway remodeling and a decline in pulmonary function, producing morbidity. Cat dander is an aeroallergen associated with asthma risk.
Objective
We sought to elucidate the mechanism of cat dander-induced inflammation-remodeling.
Methods
We identified remodeling in mucosal samples from allergic asthma by Q-RT-PCR. We developed a model of aeroallergen-induced experimental asthma by repetitive cat dander extract exposure. We measured airway inflammation using immunofluorescence, leukocyte recruitment and Q-RT-PCR. Airway remodeling was measured using histology, collagen content, myofibroblast numbers and selected reaction monitoring. Inducible NFκB-BRD4 interaction was measured by proximity ligation assay in situ.
Results
Enhanced mesenchymal signatures are observed in bronchial biopsies from patients with allergic asthma. Cat dander induces innate inflammation via NFκB signaling, followed by producing a pro-fibrogenic, mesenchymal transition (EMT) in primary human small airway epithelial cells. The IκB kinase (IKK)-NFκB signaling pathway is required for mucosal inflammation-coupled airway remodeling and myofibroblast expansion in the mouse model of aeroallergen exposure. Cat dander induces NFκB/RelA to complex with and activate BRD4, resulting in modifying the chromatin environment of inflammatory and fibrogenic genes through its atypical histone acetyltransferase (HAT) activity. A novel, small-molecule BRD4 inhibitor (ZL0454) disrupts BRD4 binding to the NFκB-RNA Pol II complex and inhibits its HAT activity. ZL0454 prevents EMT, myofibroblast expansion, IgE sensitization, and fibrosis in airways of naïve mice exposed to cat dander.
Conclusions
NFκB-inducible BRD4 activity mediates cat dander-induced inflammation and remodeling. Therapeutic modulation of the NFκB-BRD4 pathway affects allergen-induced inflammation, epithelial cell-state changes, ECM production and expansion of the subepithelial myofibroblast population.
Graphical abstract
https://ift.tt/2RMJcwv
Periorbital Rejuvenation
Publication date: Available online 13 October 2018
Source: Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Tom Shokri, Jessyka G. Lighthall
Abstract
The periorbital region, consisting of the eyebrows, upper and lower eyelids, glabella, and pericanthal region, is particularly susceptible to early signs of aging. Overall, this process is influenced by both genetic and environmental factors. Periorbital rejuvenation continues to be an area of advancement with evolution in both noninvasive and invasive techniques. In this article, we will review minimally invasive and surgical procedures in the treatment of periorbital aging.
https://ift.tt/2IV93OG
INTRODUCTION
Publication date: Available online 13 October 2018
Source: Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Michael Wilkinson
https://ift.tt/2OnhKY1
Indication and Technique of Orbital Exenteration
Publication date: Available online 12 October 2018
Source: Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Gregory M. Notz, Nicholas Purdy
Abstract
Orbital exenteration is a rare, severely disfiguring operation for the treatment of malignant orbital tumors. The tumors can arise from the orbit, metastasize to the orbit from distant sites, or invade the orbit from surrounding structures. The technique of exenteration mandates complete removal of the intraorbital contents, sometimes including the encompassing bony structures. This article will describe the indications and technique of orbital exenteration, as well as complications and several reconstructive strategies.
https://ift.tt/2ITnXVK
Anatomy of the Human Orbit
Publication date: Available online 12 October 2018
Source: Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Michael J. Wilkinson
Abstract
The contents of the human orbit develop from all embryonic germinal layers to form diverse and specialized interconnected structures, whose unified function is that of providing sight. A thorough knowledge of these structures and their inter-relationships is imperative for the head and neck surgeon. This article will discuss the structures contained within the orbit from a surgical perspective in the hope of expanding the head and neck surgeon's knowledge and comfort when treatment indication necessitates entry into this space.
https://ift.tt/2OpiR9E
Proteomic analysis of lipopolysaccharide activated human monocytes
Publication date: November 2018
Source: Molecular Immunology, Volume 103
Author(s): Mads Lausen, Thomas B.G. Poulsen, Gunna Christiansen, Kenneth Kastaniegaard, Allan Stensballe, Svend Birkelund
Abstract
Monocytes are key mediators of innate immunity and comprise an important cellular defence against invading pathogens. However, exaggerated or dysregulated monocyte activation can lead to severe immune-mediated pathology such as sepsis or chronic inflammatory diseases. Thus, detailed insight into the molecular mechanisms of monocyte activation is essential to understand monocyte-driven inflammatory pathologies. We therefore investigated the global protein changes in human monocytes during lipopolysaccharide (LPS) activation to mimic bacterial activation. Purified human monocytes were stimulated with LPS for 17 h and analyzed by state-of-the-art liquid chromatography tandem mass spectrometry (LC–MS/MS). The label-free quantitative proteome analysis identified 2746 quantifiable proteins of which 101 had a statistically significantly different abundance between LPS-stimulated cells and unstimulated controls. Additionally, 143 proteins were exclusively identified in either LPS stimulated cells or unstimulated controls. Functional annotation clustering demonstrated that LPS, most significantly, regulates proteasomal- and lysosomal proteins but in opposite directions. Thus, seven proteasome subunits were upregulated by LPS while 11 lysosomal proteins were downregulated. Both systems are critically involved in processing of proteins for antigen-presentation and together with LPS-induced regulation of CD74 and tapasin, our data suggest that LPS can skew monocytic antigen-presentation towards MHC class I rather than MHC class II. In summary, this study provides a sensitive high throughput protein analysis of LPS-induced monocyte activation and identifies several LPS-regulated proteins not previously described in the literature which can be used as a source for future studies.
https://ift.tt/2OlS12u
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