Publication date: November 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 5, Supplement
Author(s): D. Pearlman, G. Eckerwall, J. McLaren, R. Lamarca, M. Puu, C. Jorup, K. Sandin, M. Lanz
http://ift.tt/2fIjCqk
Παρασκευή 11 Νοεμβρίου 2016
O021 Efficacy of budesonide/formoterol pressurized metered-dose inhaler versus budesonide alone in children (6-<12 years) with asthma
O003 Successful treatment of attacks in hereditary angioedema with normal C1 inhibitor using prophylactic tranexamic acid
Publication date: November 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 5, Supplement
Author(s): M. Kearns, K. Reddy, S. Krishnan, C. Radojicic, A. Gonzalez-Estrada
http://ift.tt/2fqwHn3
O004 Childhood presenting hereditary angioedema is diagnosed in adulthood by non-pediatric physicians: Icatibant outcome survey findings
Publication date: November 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 5, Supplement
Author(s): H. Longhurst, W. Aberer, L. Bouillet, T. Caballero, A. Bygum, A. Grumach, A. Perrin, I. Andresen, A. Zanichelli, M. Maurer
http://ift.tt/2fDse13
O005 Improvement in hereditary angioedema diagnosis: Findings from the icatibant outcome survey
Publication date: November 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 5, Supplement
Author(s): A. Zanichelli, M. Magerl, H. Longhurst, W. Aberer, A. Bygum, T. Caballero, L. Bouillet, A. Grumach, A. Perrin, I. Andresen, M. Maurer
http://ift.tt/2fqqF68
O006 Open-label, non-randomized study of single-dose icatibant in pediatric patients with hereditary angioedema: Primary/secondary/pharmacokinetic analyses
Publication date: November 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 5, Supplement
Author(s): J. Bernstein, H. Farkas, A. Reshef, W. Aberer, T. Caballero, L. McCarthy, J. Hao, W. Nothaft, J. Schranz, H. Li
http://ift.tt/2fI9gVI
Response to “The Concept of Fragile Skin: a Case of Disease Mongering in Dermatology?”
Abstract
We thank Dr Elsner for his interest in our supplement "Fragility of epidermis in newborns, children and adolescents" recently published in this journal, but note his concern about the value of the term "fragile skin" as a scientifically useful disease definition, given the wide spectrum of conditions covered by the term [1]. Contrary to what is suggested in the letter by Dr Elsner, fragile skin is not a "disease" and should not be confounded with skin fragility existing in the repertoire of dermatological diseases requiring medical treatment using pharmaceutical interventions (e.g. disorder "skin fragility", leading to mechanical skin tears [2]), but is a perceived skin condition which can be managed by dermo-cosmetic treatments [3]. The skin as our outer defence wall protects the body against a range of microbial, chemical and physical insults and grants a homeostatic balance for the internal environment, including the protection against excessive water loss [2].
This article is protected by copyright. All rights reserved.
http://ift.tt/2fDkXOQ
Influence of interpersonal traits on patient outcomes in the treatment of chronic rhinosinusitis
Background
Patient-reported outcome measures (PROMs) measure health states in chronic rhinosinusitis (CRS) and have become the dominant metrics of treatment outcomes. Interpersonal traits (IPTs) are patient-specific factors that include personality type, perceived social support, and trust in physicians. The association of IPTs on treatment outcomes among patients with CRS has not been described previously, and IPTs may represent major clinical factors influencing treatment outcomes.
Methods
Adult patients electing medical or surgical treatment for recalcitrant CRS were prospectively enrolled into a multi-institutional, observational outcomes study. Validated measures of IPTs, including the Big Five Inventory-10 Short Version (BFI-10), Multidimensional Scale of Perceived Social Support (MSPSS), and the Trust in Physician Scale (TPS), were completed and compared with PROMs, which included the 22-item SinoNasal Outcome Test (SNOT-22), the Medical Outcomes Study Short Form-6D (SF-6D), and the Patient Health Questionnaire-2 (PHQ-2).
Results
Three hundred fifty-four participants were included and followed for an average (± standard deviation) of 16.3 (±4.8) months. Significant within-subject improvement in mean PROM scores was reported (all p <0.001). No association was detected between PROM score improvement and baseline BFI-10 or MSPSS scores (p > 0.050). Significant, but weak, absolute correlations were reported between baseline TPS scores and improvement in SNOT-22, SF-6D, and PHQ-2 total scores (p < 0.050; r ≤ 0.138).
Conclusion
Personality type and perceived social support do not associate with improvement after treatment for CRS. However, increased trust in physicians is weakly associated with greater posttreatment improvement. Further study is needed to examine the relationship between physician trust, patient satisfaction, and treatment outcomes among patients with CRS.
http://ift.tt/2eJQjB3
Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis
Background
The currently accepted treatment paradigm of treating chronic rhinosinusitis (CRS) first with appropriate medical therapy (AMT) and then with surgery if patients are refractory to AMT, has been criticized for lack of evidence. The objective of this study was to reassess the literature and establish the highest level of evidence possible regarding further management of CRS patients refractory to AMT.
Methods
This study was a systematic review (SR) with meta-analysis (MA). Adult CRS patients who received AMT and then underwent either medical or surgical therapy in moderate to high level prospective studies were included. Outcomes assessed were disease-specific quality of life (QOL), nasal endoscopy, health-state utility, missed work days, change in cardinal symptoms of CRS, economic impact, and adverse events.
Results
A total of 970 manuscripts were identified; 6 studies were ultimately included in the SR with 5 included in the MA. Compared to continued medical therapy, endoscopic sinus surgery (ESS) significantly improved patient-based QOL scores (p < 0.00001) and nasal endoscopy scores (p < 0.00001). Difference in missed work days depended heavily on patient choice of intervention. Unpooled analysis showed improvements in olfaction, health utility scores, and cost-effectiveness.
Conclusion
On meta-analysis, for CRS patients refractory to AMT, ESS significantly improves objective endoscopic scoring outcomes vs continued medical therapy alone. In patients with refractory CRS who have significant reductions in baseline QOL, ESS results in significant improvements. Continued medical therapy appears to maintain outcomes in patients with less severe baseline QOL. Unpooled analysis demonstrates improvement in health utility, olfaction, and cost-effectiveness following ESS compared to continued medical therapy alone, in medically refractory CRS.
http://ift.tt/2fDp6Cj
Fluorescein-guided intraoperative endoscopy in patients with hereditary hemorrhagic telangiectasia: first impressions
Background
Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that results in mucocutaneous telangiectasias and arteriovenous visceral malformations. Nasal telangiectasias lead to recurrent epistaxis, which affects up to 96% of patients. Different morphologic classifications and methods of visualization of nasal lesions have been described in the literature. We developed a new method of intraoperative endoscopy based on the intravenous administration of fluorescein. Preliminary data of this technique are reported.
Methods
After the intravenous administration of sodium fluorescein, an intraoperative fluorescein-guided endoscopy was carried out using photographic customized yellow filters on top of a 0-degree, 4-mm endoscope.
Results
In 2015, 65 HHT patients underwent surgery for their epistaxis in our institution, and in 7 patients (3 males, 4 females; mean age, 54 years) an intraoperative fluorescein-guided intraoperative nasal endoscopy was performed. No adverse events or complications were observed.
Conclusion
First impressions regarding the usage of this technique in HHT patients seem to be promising and positive in terms of efficacy and safety. However, further studies with larger cohorts of patients should be performed in order to better investigate the use of this method for diagnostic and surgical purposes in HHT.
http://ift.tt/2eJKbsQ
Prevention of sinonasal inflammation by a synthetic glycosaminoglycan
Background
Glycosaminoglycans (GAGs) are polysaccharides that are distributed on respiratory epithelial cells, endothelial cells, and submucosal glands. Uniquely positioned, certain GAGs exhibit anti-inflammatory properties in respiratory diseases and serve important roles in repairing mucosal surfaces and modulating mucociliary clearance. We hypothesized that topical administration of a synthetic GAG (GM-0111) would prevent sinonasal inflammation in a mouse model of rhinosinusitis (RS).
Methods
To test our hypothesis, C57BL/6 mice were intranasally administered fluorescent GM-0111, and sinonasal tissues were examined for coating and penetration ability. To test therapeutic feasibility, mice (n = 6) were given GM-0111 or hyaluronic acid (HA; 800 μg dose) prior to inducing RS with inflammatory molecule LL-37 (115 μg dose). After 24 hours, sinonasal tissues were harvested for histological and biochemical analysis of inflammatory markers (inflammatory cell infiltration, lamina propria [LP] thickening, and neutrophil enzyme myeloperoxidase [MPO]) and cell death.
Results
GM-0111 was observed within sinonasal tissues 1 hour and 24 hours after intranasal administration, indicating rapid and effective coating and penetration. GM-0111 prevented sinonasal tissues from developing inflammatory changes, with significant reductions in mast cell infiltration (p < 0.05), LP thickening (p < 0.001), and MPO levels (p < 0.01) when compared to tissues treated with LL-37 and those pretreated with HA. GM-0111 reduced cell death within sinonasal tissues in contrast to LL-37–treated tissues.
Conclusion
We report a new synthetic GAG (GM-0111) that uniformly coats and penetrates into the sinonasal mucosa to prevent sinonasal inflammation and cell death in a mouse model of RS.
http://ift.tt/2fDnE2Z
Influence of interpersonal traits on patient outcomes in the treatment of chronic rhinosinusitis
Background
Patient-reported outcome measures (PROMs) measure health states in chronic rhinosinusitis (CRS) and have become the dominant metrics of treatment outcomes. Interpersonal traits (IPTs) are patient-specific factors that include personality type, perceived social support, and trust in physicians. The association of IPTs on treatment outcomes among patients with CRS has not been described previously, and IPTs may represent major clinical factors influencing treatment outcomes.
Methods
Adult patients electing medical or surgical treatment for recalcitrant CRS were prospectively enrolled into a multi-institutional, observational outcomes study. Validated measures of IPTs, including the Big Five Inventory-10 Short Version (BFI-10), Multidimensional Scale of Perceived Social Support (MSPSS), and the Trust in Physician Scale (TPS), were completed and compared with PROMs, which included the 22-item SinoNasal Outcome Test (SNOT-22), the Medical Outcomes Study Short Form-6D (SF-6D), and the Patient Health Questionnaire-2 (PHQ-2).
Results
Three hundred fifty-four participants were included and followed for an average (± standard deviation) of 16.3 (±4.8) months. Significant within-subject improvement in mean PROM scores was reported (all p <0.001). No association was detected between PROM score improvement and baseline BFI-10 or MSPSS scores (p > 0.050). Significant, but weak, absolute correlations were reported between baseline TPS scores and improvement in SNOT-22, SF-6D, and PHQ-2 total scores (p < 0.050; r ≤ 0.138).
Conclusion
Personality type and perceived social support do not associate with improvement after treatment for CRS. However, increased trust in physicians is weakly associated with greater posttreatment improvement. Further study is needed to examine the relationship between physician trust, patient satisfaction, and treatment outcomes among patients with CRS.
http://ift.tt/2eJQjB3
Sinonasal adenoid cystic carcinoma: a population-based analysis of 694 cases
Background
Currently, limited literature exists about sinonasal adenoid cystic carcinoma (SNACC). In this study, we analyze the demographics, survival, and treatment efficacy of this rare entity.
Methods
Our study was a retrospective population-based analysis of SNACC in the Surveillance, Epidemiology, and End Results (SEER) database assessing the 40-year time-frame of 1973 to 2013.
Results
Six hundred ninety-four SNACC patients were identified; 53.2% were female and 46.8% were male. Caucasians were most commonly affected (77.1%). SNACC most often arose from the maxillary sinuses, followed by the nasal cavity. The majority of SNACC cases presented as stage IV disease. Nodal and distant metastases were present in 3.6% and 7.1% of all cases, respectively. Overall 5-, 10-, and 20-year disease-specific survival (DSS) rates were 66.5%, 41.1%, and 17.6%, respectively. The presence of distant metastasis dropped the 5-year DSS rate from 64.5% to 20.0%. Cases treated with combined surgery and adjuvant radiotherapy had a slightly improved 5-year DSS rate compared with surgery alone (73.5% vs 72.5%). Surgery alone resulted in higher 10- and 20-year DSS rates (54.2% and 36.8%, respectively) when compared with combined therapy (44.2% and 15.5%), radiotherapy alone (10.8% and 0%), and no surgery or radiotherapy (9.3% and 0%).
Conclusion
This study represents the largest cohort of SNACC patients to date. Factors that confer a survival benefit in SNACC include M0 disease, and presentation primarily in the nasal cavity. Overall low rates of nodal metastasis may not warrant the use of elective neck dissections, unless there is clinical suspicion. Modalities of therapy that include surgery greatly improve survival. Adjuvant radiotherapy appears to slightly improve 5-year disease-free survival but does not impact long-term survival.
http://ift.tt/2eJP8Sp
Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis
Background
The currently accepted treatment paradigm of treating chronic rhinosinusitis (CRS) first with appropriate medical therapy (AMT) and then with surgery if patients are refractory to AMT, has been criticized for lack of evidence. The objective of this study was to reassess the literature and establish the highest level of evidence possible regarding further management of CRS patients refractory to AMT.
Methods
This study was a systematic review (SR) with meta-analysis (MA). Adult CRS patients who received AMT and then underwent either medical or surgical therapy in moderate to high level prospective studies were included. Outcomes assessed were disease-specific quality of life (QOL), nasal endoscopy, health-state utility, missed work days, change in cardinal symptoms of CRS, economic impact, and adverse events.
Results
A total of 970 manuscripts were identified; 6 studies were ultimately included in the SR with 5 included in the MA. Compared to continued medical therapy, endoscopic sinus surgery (ESS) significantly improved patient-based QOL scores (p < 0.00001) and nasal endoscopy scores (p < 0.00001). Difference in missed work days depended heavily on patient choice of intervention. Unpooled analysis showed improvements in olfaction, health utility scores, and cost-effectiveness.
Conclusion
On meta-analysis, for CRS patients refractory to AMT, ESS significantly improves objective endoscopic scoring outcomes vs continued medical therapy alone. In patients with refractory CRS who have significant reductions in baseline QOL, ESS results in significant improvements. Continued medical therapy appears to maintain outcomes in patients with less severe baseline QOL. Unpooled analysis demonstrates improvement in health utility, olfaction, and cost-effectiveness following ESS compared to continued medical therapy alone, in medically refractory CRS.
http://ift.tt/2fDp6Cj
Fluorescein-guided intraoperative endoscopy in patients with hereditary hemorrhagic telangiectasia: first impressions
Background
Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that results in mucocutaneous telangiectasias and arteriovenous visceral malformations. Nasal telangiectasias lead to recurrent epistaxis, which affects up to 96% of patients. Different morphologic classifications and methods of visualization of nasal lesions have been described in the literature. We developed a new method of intraoperative endoscopy based on the intravenous administration of fluorescein. Preliminary data of this technique are reported.
Methods
After the intravenous administration of sodium fluorescein, an intraoperative fluorescein-guided endoscopy was carried out using photographic customized yellow filters on top of a 0-degree, 4-mm endoscope.
Results
In 2015, 65 HHT patients underwent surgery for their epistaxis in our institution, and in 7 patients (3 males, 4 females; mean age, 54 years) an intraoperative fluorescein-guided intraoperative nasal endoscopy was performed. No adverse events or complications were observed.
Conclusion
First impressions regarding the usage of this technique in HHT patients seem to be promising and positive in terms of efficacy and safety. However, further studies with larger cohorts of patients should be performed in order to better investigate the use of this method for diagnostic and surgical purposes in HHT.
http://ift.tt/2eJKbsQ
Prevention of sinonasal inflammation by a synthetic glycosaminoglycan
Background
Glycosaminoglycans (GAGs) are polysaccharides that are distributed on respiratory epithelial cells, endothelial cells, and submucosal glands. Uniquely positioned, certain GAGs exhibit anti-inflammatory properties in respiratory diseases and serve important roles in repairing mucosal surfaces and modulating mucociliary clearance. We hypothesized that topical administration of a synthetic GAG (GM-0111) would prevent sinonasal inflammation in a mouse model of rhinosinusitis (RS).
Methods
To test our hypothesis, C57BL/6 mice were intranasally administered fluorescent GM-0111, and sinonasal tissues were examined for coating and penetration ability. To test therapeutic feasibility, mice (n = 6) were given GM-0111 or hyaluronic acid (HA; 800 μg dose) prior to inducing RS with inflammatory molecule LL-37 (115 μg dose). After 24 hours, sinonasal tissues were harvested for histological and biochemical analysis of inflammatory markers (inflammatory cell infiltration, lamina propria [LP] thickening, and neutrophil enzyme myeloperoxidase [MPO]) and cell death.
Results
GM-0111 was observed within sinonasal tissues 1 hour and 24 hours after intranasal administration, indicating rapid and effective coating and penetration. GM-0111 prevented sinonasal tissues from developing inflammatory changes, with significant reductions in mast cell infiltration (p < 0.05), LP thickening (p < 0.001), and MPO levels (p < 0.01) when compared to tissues treated with LL-37 and those pretreated with HA. GM-0111 reduced cell death within sinonasal tissues in contrast to LL-37–treated tissues.
Conclusion
We report a new synthetic GAG (GM-0111) that uniformly coats and penetrates into the sinonasal mucosa to prevent sinonasal inflammation and cell death in a mouse model of RS.
http://ift.tt/2fDnE2Z
Sinonasal adenoid cystic carcinoma: a population-based analysis of 694 cases
Background
Currently, limited literature exists about sinonasal adenoid cystic carcinoma (SNACC). In this study, we analyze the demographics, survival, and treatment efficacy of this rare entity.
Methods
Our study was a retrospective population-based analysis of SNACC in the Surveillance, Epidemiology, and End Results (SEER) database assessing the 40-year time-frame of 1973 to 2013.
Results
Six hundred ninety-four SNACC patients were identified; 53.2% were female and 46.8% were male. Caucasians were most commonly affected (77.1%). SNACC most often arose from the maxillary sinuses, followed by the nasal cavity. The majority of SNACC cases presented as stage IV disease. Nodal and distant metastases were present in 3.6% and 7.1% of all cases, respectively. Overall 5-, 10-, and 20-year disease-specific survival (DSS) rates were 66.5%, 41.1%, and 17.6%, respectively. The presence of distant metastasis dropped the 5-year DSS rate from 64.5% to 20.0%. Cases treated with combined surgery and adjuvant radiotherapy had a slightly improved 5-year DSS rate compared with surgery alone (73.5% vs 72.5%). Surgery alone resulted in higher 10- and 20-year DSS rates (54.2% and 36.8%, respectively) when compared with combined therapy (44.2% and 15.5%), radiotherapy alone (10.8% and 0%), and no surgery or radiotherapy (9.3% and 0%).
Conclusion
This study represents the largest cohort of SNACC patients to date. Factors that confer a survival benefit in SNACC include M0 disease, and presentation primarily in the nasal cavity. Overall low rates of nodal metastasis may not warrant the use of elective neck dissections, unless there is clinical suspicion. Modalities of therapy that include surgery greatly improve survival. Adjuvant radiotherapy appears to slightly improve 5-year disease-free survival but does not impact long-term survival.
http://ift.tt/2eJP8Sp
Drosophila ubiquitin E3 ligase dSmurf is required for synapse remodeling and axon pruning by glia
Source:Journal of Genetics and Genomics
Author(s): Changyan Chen, Shuai Yin, Wenze Cao, Margaret S. Ho
http://rss.sciencedirect.com/action/redirectFile?&zone=main¤tActivity=feed&usageType=outward&url=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%3F_ob%3DGatewayURL%26_origin%3DIRSSSEARCH%26_method%3DcitationSearch%26_piikey%3DS1673852716301722%26_version%3D1%26md5%3D9aa1a3234d24369f6d11e7d58236fd3c
Genomic Insights in Gynecologic Cancer
Source:Current Problems in Cancer
Author(s): Erika Roddy, Jocelyn Chapman
Recent technological advances in DNA sequencing technology have enabled a remarkably detailed understanding of the molecular changes that define gynecologic and other cancers. Several groups have carried out large-scale genomic analyses of ovarian, uterine, and most recently, cervical cancer. These analyses have led to new insights into the molecular changes characterizing these cancers, which provides insight into clinical outcomes. These molecular characterizations have similarly led to new genomic-based classification schemas, which may better stratify clinical outcomes, help prognosticate and guide treatments. Discovery of characteristic mutations may also provide potential new targets for molecularly targeted chemotherapies, as has been already described with PARP inhibitors and ovarian cancer. The purpose of this review is to provide an overview of the defining molecular abnormalities and markers in gynecologic cancer, to discuss the clinical implications and to provide a comprehensive view of the current state of genomic knowledge in gynecologic cancer.
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Targeting Fibroblast Growth Factor Pathways in Endometrial Cancer
Source:Current Problems in Cancer
Author(s): Boris Winterhoff, Gottfried E. Konecny
Novel treatments that improve outcomes for patients with recurrent or metastatic endometrial cancer (EC) remain an unmet need. Aberrant signaling by fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) has been implicated in several human cancers. Activating mutations in FGFR2 have been found in up to 16% of ECs, suggesting an opportunity for targeted therapy. This review summarizes the role of the FGF pathway in angiogenesis and EC and provides an overview of FGFR-targeted therapies under clinical development for the treatment of EC.
http://ift.tt/2fIfRB8
Developmental changes in autonomic emotional response during an executive functional task: A pupillometric study during Wisconsin card sorting test
Source:Brain and Development
Author(s): Tetsuo Ohyama, Yoshimi Kaga, Yusuke Goto, Kakuro Aoyagi, Sayaka Ishii, Hideaki Kanemura, Kanji Sugita, Masao Aihara
ObjectiveThe autonomic nervous system has a deep relationship with the cognitive network when performing cognitive tasks. We hypothesize that autonomic emotional responses can affect cognitive function, especially executive function. The aim of this study was to clarify the involvement of the autonomic system during an executive functional task via developmental changes assessed using pupillometry.Subjects and methodsSubjects were 16 healthy children and 9 healthy adults. Children were divided into 3 groups (Group A, 7–9years; Group B, 10–14years; Group C, 15–17years). Pupil diameter was recorded using an eye mark recorder during cognitive shift (CS) during the Wisconsin card sorting test (WCST). The rate of pupil variations was integrated and compared within each group, focusing on performance during CS.ResultsCategories achieved (CA) in the behavioral results of WCST increased with age, with significant differences between Group A and other groups. The change of pupillary diameter was increased with CS and decreased at the correct answers after CS in adults. Changes of pupillary diameter with CS showed a linear increase with age, and the pattern of the pupillary response at the age of 10–14years was comparable to adults. The integrated rate of pupil diameter with CS increased with age, and there was a significant difference between Group A and adults. In addition, the degree of mydriasis correlated with the number of CA.ConclusionThese findings suggest that autonomic emotional response play an important role as a part of the process for executive function.
http://ift.tt/2eJGdjL
Growth of Headache Research: A 1983-2014 bibliometric study
Aim
This study charts the growth of the scientific journal literature on headache for 30+ years (1983–2014).
MethodsUsing the Web of Science, articles published in four two-year periods (1983–1984, 1993–1994, 2003–2004, 2013–2014) from journals indexed in the Science Citation Index Expanded database were retrieved and analyzed.
ResultsFrom 1983–1984 to 2013–2014, the scientific literature on headache increased nearly fourfold (3.8) from 468 to 1776 articles; the number of participating countries more than doubled (26 to 67); and the two most prolific countries in each period were the USA and Italy. While several European countries (Italy, Germany, UK and Denmark) were among the top 10 in each period, the notable appearance of Turkey, China and Brazil among the top 10 in 2013–2014 indicates the growing geographic spread of publications on headache research. Meanwhile, the comet-like distribution of journals has not changed: two journals, Headache and Cephalalgia, persist throughout as the nucleus, with the tail increasing more than threefold from 141 journals in 1983–1984 to 462 in 2013–2014.
ConclusionOur study follows the recent growth and spread of the scientific literature on headache research and should stimulate further bibliometric investigation in this field.
http://ift.tt/2fqlliT
Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: A retrospective claims analysis
Background
Migraine prevention guidelines recommend oral prophylactic medications for patients with frequent headache. This study examined oral migraine preventive medication (OMPM) treatment patterns by evaluating medication persistence, switching, and re-initiation in patients with chronic migraine (CM).
MethodsA retrospective US claims analysis (Truven Health MarketScan® Databases) evaluated patients ≥18 years old diagnosed with CM who had initiated an OMPM between 1 January, 2008 and 30 September, 2012. Treatment persistence was measured at six and 12 months' follow-up. Time-to-discontinuation was assessed for each OMPM and compared using Cox regression models. Among those who discontinued, the proportion that switched OMPMs within 60 days or re-initiated treatment between 61 to 365 days, and their associated persistence rates, were also assessed.
ResultsA total of 8707 patients met the inclusion/exclusion criteria. Persistence to the initial OMPM was 25% at six months and 14% at 12 months. Based on Kaplan-Meier curves, a sharp decline of patients discontinuing was observed by 30 days, and approximately half discontinued by 60 days. Similar trends in time-to-discontinuation were seen following the second or third OMPM. Amitriptyline, gabapentin, and nortriptyline had significantly higher likelihood of non-persistence compared with topiramate. Among patients who discontinued, 23% switched to another prophylactic and 41% re-initiated therapy within one year. Among patients who switched, persistence was between 10 to 13% and among re-initiated patients, persistence was between 4 to 8% at 12 months.
ConclusionsPersistence to OMPMs is poor at six months and declines further by 12 months. Switching between OMPMs is common, but results indicate that persistence worsens as patients cycle through various OMPMs.
http://ift.tt/2eJJdwF
The role of interleukin-22 in pityriasis rosea
Summary
Background
Pityriasis rosea (PR) is an exanthematous disease related to reactivation of human herpes virus (HHV) types 6 and 7. The pathogenesis and cytokine profile of PR are still poorly understood.There is a large amount of evidence indicating a viral aetiology for PR.
Aim
To measure the serum level of interleukin (IL)-22, a cytokine expressed by T helper (Th)17 cells in patients with PR to explore the possible association of IL-22 with the pathogenesis of the disease.
Methods
This case–control study enrolled 25 patients with PR (mean ± SD age 20 ± 12 years) and a control group of 25 apparently healthy individuals (mean age 18 ± 12.1 years). Blood samples were collected from both patients and controls to measure serum IL-22. Scoring of PR was performed using the Pityriasis Rosea Severity Score (PRSS).
Results
There was a statistically significant difference in IL-22 serum level between the patient and control groups. The IL-22 serum level increased with increase in disease severity (PRSS), extent and duration.
Conclusion
Through its proinflammatory cytokines, IL-22 plays a role in the inflammatory process of PR.
http://ift.tt/2fqfJpa
Different sample treatments for the determination of ICM-XR in fish samples followed by LC-HRMS
Publication date: 15 January 2017
Source:Talanta, Volume 163
Author(s): Mireia Núñez, Francesc Borrull, Núria Fontanals, Eva Pocurull
Iodinated X-ray contrast media (ICM-XR) are a group of pharmaceuticals widely used in medicine. Due to their low biodegradation rate, which makes their removal at wastewater treatment plants difficult, and the high doses at which they are administered, they have been detected in aquatic environments. In the present paper, a method for the quantitative determination of a group of ICM-XR in different fish species was developed and validated for the first time. Two extraction techniques were compared: pressurised liquid extraction (PLE) and QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe), with PLE being selected, followed by liquid chromatography-high resolution mass spectrometry. In addition, several clean-up strategies were evaluated. The optimised method provided PLE recoveries ranging from 60% to 88% and limits of detection ranging from 5ng/g to 25ng/g (dry weight). The method was applied in order to evaluate the presence of the selected ICM-XR in different fish species.
Graphical abstract
http://ift.tt/2fI6gtZ
Arterial Spin Labelling Shows Functional Depression of Non-Lesion Tissue in Chronic Wernicke’s Aphasia
Source:Cortex
Author(s): Holly Robson, Karsten Specht, Helen Beaumont, Laura M. Parkes, Karen Sage, Matthew A. Lambon Ralph, Roland Zahn
Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow is rarely investigated in chronic stroke. This study investigated cerebral blood flow in individuals with chronic Wernicke's aphasia and examined the relationship between lesion, cerebral blood flow and neuropsychological impairment.Arterial spin labelling cerebral blood flow imaging and structural MRIs were collected in 12 individuals with chronic Wernicke's aphasia and 13 age-matched control participants. Joint independent component analysis (jICA) investigated the relationship between structural lesion and hypoperfusion. Partial correlations explored the relationship between lesion, hypoperfusion and language measures.Joint ICA revealed significant differences between the control and WA groups reflecting a large area of structural lesion in the left posterior hemisphere and an associated area of hypoperfusion extending into grey matter surrounding the lesion. Small regions of remote cortical hypoperfusion were observed, ipsilateral and contralateral to the lesion. Significant correlations were observed between the neuropsychological measures (naming, repetition, reading and semantic association) and the jICA component of interest in the WA group. Additional ROI analyses found a relationship between perfusion surrounding the core lesion and the same neuropsychological measures.This study found that core language impairments in chronic Wernicke's aphasia are associated with a combination of structural lesion and abnormal perfusion in non-lesioned tissue. This indicates that post-stroke impairments are due to a wider disruption of neural function than observable on structural T1w MRI.
http://ift.tt/2fDc2wN
Electrophysiological responses to symmetry presented in the left or in the right visual hemifield
Source:Cortex
Author(s): Damien Wright, Alexis D.J. Makin, Marco Bertamini
Symmetry is a highly salient feature in the visual world, abundant in both man-made and natural objects. In particular, humans find reflectional symmetry most salient. Electrophysiological work on symmetry perception has identified a difference wave known as the Sustained Posterior Negativity (SPN) originating from extrastriate areas. Amplitude is more negative for symmetrical than random patterns, from around 200ms after stimulus onset. For the first time, we report responses to patterns presented exclusively in one hemifield. Participants were presented with reflection or random dot patterns to the left and right of fixation (3.2º). They judged whether the patterns were light red or dark red in colour. In Experiment 1, the pair always included one symmetrical and one random pattern. In Experiments 2 and 3 we varied the information presented contralaterally. The SPN was generated separately in each hemisphere in response to what was presented in the contralateral visual hemifield (a lateralised SPN). We conclude that a symmetry-sensitive network of extrastriate areas can be activated independently in each cerebral hemisphere.
http://ift.tt/2fHVrqe
The role of interleukin-22 in pityriasis rosea
Summary
Background
Pityriasis rosea (PR) is an exanthematous disease related to reactivation of human herpes virus (HHV) types 6 and 7. The pathogenesis and cytokine profile of PR are still poorly understood.There is a large amount of evidence indicating a viral aetiology for PR.
Aim
To measure the serum level of interleukin (IL)-22, a cytokine expressed by T helper (Th)17 cells in patients with PR to explore the possible association of IL-22 with the pathogenesis of the disease.
Methods
This case–control study enrolled 25 patients with PR (mean ± SD age 20 ± 12 years) and a control group of 25 apparently healthy individuals (mean age 18 ± 12.1 years). Blood samples were collected from both patients and controls to measure serum IL-22. Scoring of PR was performed using the Pityriasis Rosea Severity Score (PRSS).
Results
There was a statistically significant difference in IL-22 serum level between the patient and control groups. The IL-22 serum level increased with increase in disease severity (PRSS), extent and duration.
Conclusion
Through its proinflammatory cytokines, IL-22 plays a role in the inflammatory process of PR.
http://ift.tt/2fqfJpa
Minimally Invasive, Single-Stage, Multilevel Surgery for Obstructive Sleep Apnea in Asian Patients.
| Related Articles |
Minimally Invasive, Single-Stage, Multilevel Surgery for Obstructive Sleep Apnea in Asian Patients.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 10;:
Authors: Lin HC, Friedman M, Chang HW, Bonzelaar L, Salapatas AM, Lin MC, Huang KT
Abstract
Importance: This study adds to the literature on the efficacy and low complication rates associated with minimally invasive, single-stage, multilevel surgery for Asian adults with obstructive sleep apnea (OSA) for whom conservative treatment had failed. Overall, our experience has produced results that make this procedure an option for select patients with snoring and OSA.
Objective: To investigate the effectiveness and safety of anatomy-based, minimally invasive, single-stage, multilevel surgery in the treatment of OSA in an Asian population.
Design, Setting, and Participants: This retrospective study enrolled 59 consecutive patients with OSA from a tertiary academic medical center who had multilevel obstruction and unsuccessful conservative therapy and then underwent minimally invasive, single-stage, multilevel surgery. The subjective symptoms and objective polysomnographic findings were collected preoperatively and at a minimum of 3 months postoperatively. The Global Patient Assessment questionnaire was used to assess patient satisfaction after minimally invasive, single-stage, multilevel surgery.
Main Outcomes and Measures: Scores on the Epworth Sleepiness Scale and bed partner evaluation of patient's snoring on a visual analog scale (scale of 0-10, with 0 indicating no snoring and 10 indicating the bed partner to leave the room or sleep separately, as assessed by the bed partner). The primary outcomes are a 50% decrease in bed partner's snoring visual analog scale level postoperatively and an improvement of 50% or more in apnea-hypopnea index by an at least 3-month follow-up. Adverse events and patient-reported quality measures were also assessed.
Results: Forty-seven patients (36 men and 11 women; mean [SD], 47.3 [10.9] years) with a minimum 3-month follow-up and complete data were included in the analysis. None of the patients had serious perioperative or postoperative complications. Three months postoperatively, the mean (SD) scores on the Epworth Sleepiness Scale and bed partner evaluation of patient's snoring on the visual analog scale decreased from 11.6 (4.3) to 9.2 (3.1), with a mean (SD) difference of -2.4 (3.7) (95% CI, -3.5 to -1.3), and 9.4 (1.5) to 3.9 (1.9), with a mean (SD) difference of -5.6 (2.0) (95% CI, -6.2 to -5.0), respectively. The mean (SD) apnea-hypopnea index and lowest oxygen saturation changed from 30.5 (18.8) to 26.0 (16.5), with a mean (SD) difference of -4.5 (14.1) (95% CI, -8.6 to -0.3), and 78.2% (9.9%) to 80.8% (8.2%), with a mean (SD) difference of +2.6 (8.7) (95% CI, 0-5.1), respectively. The surgical response rate was 46.8% (22 of 47 patients) (95% CI, 32.5%-61.1%). The classical success rate was 14.9% (7 of 47 patients) (95% CI, 6.2%-28.3%).
Conclusions and Relevance: This study reveals the improvement of the 2 relevant clinical outcomes in snoring severity and daytime sleepiness after minimally invasive, single-stage, multilevel surgery for patients with OSA but the limited effects on the polysomnographic parameters. Although the current role of minimally invasive, single-stage, multilevel surgery for Asian adults with OSA remains to be established, it is hoped that ongoing and future studies will solidify their role in the treatment of OSA.
PMID: 27832273 [PubMed - as supplied by publisher]
http://ift.tt/2fCLOKS
An Expansile Mass Following Central Lymph Node Dissection.
| Related Articles |
An Expansile Mass Following Central Lymph Node Dissection.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 10;:
Authors: Lasker GF, Raggio B, Kandil E
PMID: 27832266 [PubMed - as supplied by publisher]
http://ift.tt/2fHT1YS
No causal impact of serum vascular endothelial growth factor level on temporal changes in body mass index in Japanese male workers: a five-year longitudinal study
Abstract
Purpose:
It has been reported that adipocytes secrete vascular endothelial growth factor. Therefore, we conducted a 5-year longitudinal epidemiological study to further elucidate the association between vascular endothelial growth factor levels and temporal changes in body mass index.
Methods:
Our study subjects were Japanese male workers, who had regular health check-ups. Vascular endothelial growth factor levels were measured at baseline. To examine the association between vascular endothelial growth factor levels and overweight, we calculated the odds ratio using a multivariate logistic regression model. Moreover, linear mixed effect models were used to assess the association between vascular endothelial growth factor level and temporal changes in body mass index during the 5-year follow-up period.
Results:
Vascular endothelial growth factor levels were marginally higher in subjects with a body mass index greater than 25 kg/m2 compared with in those with a body mass index less than 25 kg/m2 (505.4 vs. 465.5 pg/mL, P = 0.1) and were weakly correlated with leptin levels (β: 0.05, P = 0.07). In multivariate logistic regression, subjects in the highest vascular endothelial growth factor quantile were significantly associated with an increased risk for overweight compared with those in the lowest quantile (odds ratio 1.65, 95 % confidential interval: 1.10–2.50). Moreover P for trend was significant (P for trend = 0.003). However, the linear mixed effect model revealed that vascular endothelial growth factor levels were not associated with changes in body mass index over a 5-year period (quantile 2, β: 0.06, P = 0.46; quantile 3, β: −0.06, P = 0.45; quantile 4, β: −0.10, P = 0.22; quantile 1 as reference).
Conclusions:
Our results suggested that high vascular endothelial growth factor levels were significantly associated with overweight in Japanese males but high vascular endothelial growth factor levels did not necessarily cause obesity.
http://link.springer.com/10.1007/s12020-016-1165-5
Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome.
| Related Articles |
Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 10;:
Authors: Wineland A, Menezes MD, Shimony JS, Shinawi MS, Hullar TE, Hirose K
Abstract
Importance: CHARGE syndrome refers to a syndrome involving coloboma, heart defects, atresia choanae, retardation of growth and development, genitourinary disorders, and ear anomalies. However, Verloes revised the characteristics of CHARGE syndrome in 2005 to define this syndrome more broadly. Deficiency of the semicircular canals is now a major criterion for CHARGE syndrome.
Objective: To characterize patients with CHARGE syndrome at our center using Verloes' criteria and to reevaluate the nomenclature for this condition.
Design, Setting, and Participants: We performed a medical chart review of patients with CHARGE syndrome and reviewed their temporal bone imaging studies at a tertiary care children's hospital affiliated with Washington University in St Louis. Two authors independently reviewed each imaging study (A.W. and K.H.). Radiologic studies, physical findings, genetic tests, and other diagnostic tests were included. Patients with no temporal bone imaging studies were excluded.
Results: Eighteen children were included in this study; 13 children (72%) were male, and the mean (median; range) age of patients at the time of inner ear imaging studies was 2 years (4.5 years; 8 months to 8 years). Coloboma was present in 13 patients (72%) and choanal atresia in 5 (28%); semicircular canal anomalies were present in all patients. Additionally, 13 patients (72%) were diagnosed as having hindbrain anomalies, 17 (94%) as having endocrine disorders, 17 (94%) as having mediastinal organ malformations, and all as having middle or external ear abnormalities and development delay. Cleft lip and cleft palate were found in 6 of 14 patients (43%) who did not have choanal atresia. We tested 16 patients for mutations in the CHD7 gene; 10 were positive (63%) for mutations, 4 (25%) were negative, and 2 (13%) were inconclusive.
Conclusions and Relevance: Semicircular canal anomalies were the most consistent finding in our patients with CHARGE syndrome. Given the high prevalence of semicircular canal hypoplasia and importance of imaging for diagnosing CHARGE syndrome, we propose changing the term CHARGE syndrome to 3C syndrome to emphasize the importance of the semicircular canals and to recall the 3 major criteria for diagnosis: coloboma, choanal atresia, and semicircular canal anomaly. The nomenclature would also reference the 3 semicircular canals in each ear. This new name for CHARGE syndrome would provide a mnemonic and focus the disease on the most important clinical criteria for diagnosis.
PMID: 27832265 [PubMed - as supplied by publisher]
https://www.ncbi.nlm.nih.gov/pubmed/27832265?dopt=Abstract
Epidemiology of Squamous Cell Carcinoma of the Lip in the United States: A Population-Based Cohort Analysis.
| Related Articles |
Epidemiology of Squamous Cell Carcinoma of the Lip in the United States: A Population-Based Cohort Analysis.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 10;:
Authors: Han AY, Kuan EC, Mallen-St Clair J, Alonso JE, Arshi A, St John MA
Abstract
Importance: Squamous cell carcinoma of the lip (lip SCC) composes more than 25% of all oral cancers. Most of the demographic and prognostic indicators for lip SCC are only available through retrospective case series.
Objective: To examine the incidence, treatment, overall survival, and disease-specific survival (DSS) of patients with lip SCC.
Design, Setting, and Participants: Population-based cohort analysis using the Surveillance, Epidemiology, and End Results database identified patients with lip SCC between January 1, 1973, and December 31, 2012.
Main Outcomes and Measures: Overall survival and DSS.
Results: A total of 15 832 cases of lip SCC were identified. The cohort was composed of 12 945 men (81.8%) and 2887 women (18.2%). The mean age at diagnosis was 66.1 years. White patients accounted for 98.4% of the cases. Most of the tumors presented in the lower lip (77.8% external and 10.2% mucosal), whereas the external upper lip, mucosal upper lip, and the oral commissure represented 8%, 1%, and 1.2% of all cases, respectively. Of the patients, 91.2% underwent surgical therapy, 7.7% received radiation therapy, and 4.7% received both. Overall survival at 2 years, 5 years, and 10 years was 85.5%, 69.9%, and 50.2%, respectively. Multivariate analysis revealed that age, primary site, T stage, and N stage were determinants of overall survival and DSS. Kaplan-Meier survival analysis showed that SCC of the upper and lower lip had similar overall survival (163.6 months vs 163.8 months) and DSS (418.6 months vs 423.6 months). In contrast, SCC of the oral commissure had significantly lower overall survival (128.5 months) and DSS (286.7 months).
Conclusions and Relevance: Our study demonstrates that lip SCC predominantly affects white men in their mid-60s. The determinants of survival for lip SCC include age at diagnosis, primary site, T stage, and N stage. Squamous cell carcinoma of the upper lip and lower lip had similar survival, whereas SCC of the oral commissure was associated with decreased survival.
PMID: 27832256 [PubMed - as supplied by publisher]
http://ift.tt/2fCMfEZ
Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
| Related Articles |
Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 10;:
Authors: Chen MM, Harris JP, Hara W, Sirjani D, Divi V
Abstract
Importance: The guidelines for head and neck cancer recommend consideration of adjuvant postoperative radiotherapy (PORT) for patients with pT1N1 or pT2N1 disease in the absence of other adverse features. This recommendation was recently changed for oropharyngeal (OP) squamous cell carcinoma (SCC).
Objective: To examine the use and outcomes of PORT for N1 OP SCC and oral cavity (OC) SCC.
Design, Setting, and Participants: This retrospective cohort study identified 1467 adult patients with OC SCC and 790 patients with OP SCC with pT1N1 or pT2N1 disease in the absence of other adverse features from the National Cancer Database from January 1, 2004, to December 31, 2013. Patients who received adjuvant chemotherapy or palliative radiotherapy or who had adverse pathologic features were excluded. Statistical analysis included χ2 tests and Cox proportional hazards regression analysis. Data were analyzed from November 10, 2015, to June 30, 2016.
Main Outcomes and Measures: Overall survival.
Results: Of the 1467 patients with OC SCC (842 men [57.4%]; 625 women [42.6%]; mean [SD] age, 61.3 [13.8] years), 740 (50.4%) received PORT. Of the 790 patients with OP SCC (584 men [73.9%]; 206 women [26.1%]; mean [SD] age, 58.2 [10.3] years), 449 (56.8%) received PORT. After controlling for patient demographics, pathologic characteristics, and hospital-level variables, PORT was associated with improved overall survival for patients with OC SCC (hazard ratio [HR], 0.76; 95% CI, 0.63-0.92) and OP SCC (HR, 0.62; 95% CI, 0.41-0.92) with pN1 disease without adverse features. On stratified analysis, this association persisted for patients younger than 70 years (OC SCC HR, 0.77; 95% CI, 0.61-0.97; OP SCC HR, 0.48; 95% CI, 0.31-0.75) and those with pT2 disease (OC SCC HR, 0.64; 95% CI, 0.43-0.96; OP SCC HR, 0.56; 95% CI, 0.32-0.95), but there was no association with overall survival among patients 70 years or older (OC SCC HR, 0.78; 95% CI, 0.58-1.06; OP SCC HR, 1.55; 95% CI, 0.63-3.82) and those with pT1 disease (OC SCC HR, 0.80; 95% CI, 0.60-1.07; OP SCC HR, 0.66; 95% CI, 0.35-1.24).
Conclusions and Relevance: PORT may be associated with improved survival in patients with pN1 OC and OP SCC, especially in those younger than 70 years or those with pT2 disease.
PMID: 27832255 [PubMed - as supplied by publisher]
http://ift.tt/2eJdA6p
Living in a Patient-Centric Universe.
| Related Articles |
Living in a Patient-Centric Universe.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 10;:
Authors: Kraus DH
Abstract
Patients with head and neck cancer face a number of challenges in terms of treatment, cure of their underlying malignant condition, and quality of survivorship. This presentation will focus on the patient perception of both the quality of care and the empathy and availability of the head and neck oncology team. It has become evident that the quality of survivorship plays a central role in the patient's decision-making process. The process of decision making by the patient facing head and neck cancer and the impact on treatment choices will be explored. The ability of the patient and her or his support system to navigate through the increasingly complicated health care system will be considered, with an emphasis on strategies for success. Finally, the role of the of the head and neck surgeon, and the need for physician wellness in predicating successful patient outcomes will be considered. The ultimate goal of achieving optimal care, superior patient outcomes, and patient satisfaction is the true objective of the concept of living in a patient-centric universe.
PMID: 27832247 [PubMed - as supplied by publisher]
http://ift.tt/2fCIAqx
Morel-Lavallée Injuries
Source:Academic Radiology
Author(s): James A. Spain, Matthew Rheinboldt, David Parrish, Eric Rinker
Morel-Lavallée lesions are relatively rare closed degloving injuries caused by a shearing force resulting in separation of the dermis and the hypodermis from the subjacent deeper fascia. Although most commonly encountered lateral to the greater trochanter, these injuries may occur throughout the body in a variety of locations. Separation of the hypodermal tissue planes results in a complex serosanguinous fluid collection with areas of internal fat necrosis. The imaging appearance is variable and nonspecific, potentially mimicking superficial hemorrhagic bursitis, or cystic or necrotic primary soft tissue neoplasms. If not treated in the acute or early subacute setting, these collections are at risk of superinfection, overlying tissue necrosis, and continued expansion. In this article, we will review the pathophysiology, cross-sectional imaging features, and differential diagnostic considerations of Morel-Lavallée lesions as well as discuss management and treatment options.
http://rss.sciencedirect.com/action/redirectFile?&zone=main¤tActivity=feed&usageType=outward&url=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%3F_ob%3DGatewayURL%26_origin%3DIRSSSEARCH%26_method%3DcitationSearch%26_piikey%3DS1076633216303269%26_version%3D1%26md5%3D64fc618ce7665dcf050be8bce78c5cc4
Escalating and de-escalating treatment in HER2-positive early breast cancer
Source:Cancer Treatment Reviews
Author(s): Heikki Joensuu
The current standard adjuvant systemic treatment of early HER2-positive breast cancer consists of chemotherapy plus 12 months of trastuzumab, with or without endocrine therapy. Several trials have investigated modifications of the standard treatment that are shorter and less resource-demanding (de-escalation) or regimens that aim at dual HER2 inhibition or include longer than 12 months of HER2-targeted treatment (escalation). Seven randomized trials investigate shorter than 12 months of trastuzumab treatment duration. The shorter durations were not statistically inferior to the 1-year duration in the 3 trials with survival results available, but 2 of the trials were small and 1 had a relatively short follow-up time of the patients at the time of reporting. The pathological complete response (pCR) rates were numerically higher in all 9 randomized trials that compared chemotherapy plus dual HER2 inhibition consisting of trastuzumab plus either lapatinib, neratinib, or pertuzumab with chemotherapy plus trastuzumab as neoadjuvant treatments, but the superiority of chemotherapy plus dual HER2-inhibition over chemotherapy plus trastuzumab remains to be demonstrated in the adjuvant setting. One year of adjuvant trastuzumab was as effective as 2 years of trastuzumab in the HERA trial, and was associated with fewer side-effects. Extending 1-year adjuvant trastuzumab treatment with 1 year of neratinib improved disease-free survival in the ExteNET trial, but the patient follow-up times are still short, and no overall survival benefit was reported. Several important trials are expected to report results in the near future and may modify the current standard.
http://ift.tt/2fHLR6K
The expanding role of stereotactic body radiation therapy in oligometastatic solid tumors: what do we know and where are we going?
Source:Cancer Treatment Reviews
Author(s): Julian C. Hong, Joseph K. Salama
The spectrum hypothesis posits that there are distinct clinical states of metastatic progression. Early data suggest that aggressive treatment of more biologically indolent metastatic disease, characterized by metastases limited in number and destination organ, may offer an opportunity to alter the disease course, potentially allowing for longer survival, delay of systemic therapy, or even cure. The development of stereotactic body radiation therapy (SBRT) has opened new avenues for the treatment of oligometastatic disease. Early data support the use of SBRT for treating oligometastases in a number of organs, with promising rates of treated metastasis control and overall survival. Ongoing investigation is required to definitively establish benefit, determine the appropriate treatment regimen, refine patient selection, and incorporate SBRT with systemic therapies.
http://ift.tt/2fq8UDZ
ESR1 mutations: moving towards guiding treatment decision-making in metastatic breast cancer patients
Source:Cancer Treatment Reviews
Author(s): Lindsay Angus, Nick Beije, Agnes Jager, John W. M. Martens, Stefan Sleijfer
Mutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning that the receptor is active in absence of its ligand estrogen, conferring resistance against several endocrine agents. While recent clinical studies reported that the occurrence of ESR1 mutations is rare in primary breast cancer tumors, these mutations are more frequently observed in metastatic tissue and circulating cell-free DNA of MBC patients pretreated with endocrine therapy. Given the assumed impact that the presence of ESR1 mutations has on outcome to endocrine therapy, assessing ESR1 mutations in MBC patients is likely to be of significant interest to further individualize treatment for MBC patients. Here, ESR1 mutation detection methods and the most relevant pre-clinical and clinical studies on ESR1 mutations regarding endocrine resistance are reviewed, with particular interest in the ultimate goal of guiding treatment decision-making based on ESR1 mutations.
http://ift.tt/2fHNjpQ
Hand, foot and mouth disease: an overview of clinical features in adult patients
Abstract
Hand, foot and mouth disease (HFMD) mainly affects children aged <5 years and is caused by several serotypes of enteroviruses, more frequently Enterovirus 71 (EV71) and Coxsackie A16 (CA16)1. The disease presents with vesicles in the mouth, hands, feet and buttocks. Only 1% of infected adults develop clinical manifestations, probably as a result of immunological memory1. Nevertheless, in the atypical HFMD caused by Coxsackie virus A6 (CVA6) the involvement of immunocompetent adults has been recently described2-6.
This article is protected by copyright. All rights reserved.
http://ift.tt/2eJfpAg
The Concept of “Fragile Skin”: A Case of Disease Mongering in Dermatology?
Abstract
"Disease mongering" is a term proposed by medical journalist Lynn Payer in 1992 as "trying to convince essentially well people that they are sick, or slightly sick people that they are very ill" [1]. Scientifically, it has been defined as the "selling of sickness that widens the boundaries of illness in order to grow markets for those who sell and deliver treatments" [2]. While the promotion of medical products to physicians is a legal right of manufacturers that may serve a legitimate purpose, i.e. informing physicians on innovative treatment options for their patients, disease mongering refers to the medicalisation of conditions that do not fulfil the definition of disease.
This article is protected by copyright. All rights reserved.
http://ift.tt/2eYG5xM
Fast evaluation and monitoring of ingenol mebutate treatment of multiple basal cell carcinomas by in vivo hand held reflectance confocal microscopy
Abstract
Patients presenting multiple basal cell carcinomas (BCCs) are increasing and their management often entails a challenge for dermatologists1. In vivo reflectance confocal microscopy (RCM) has demonstrated in a recent metanalysis a very good performance in the diagnosis of BCC, opening a new alternative in the evaluation of these patients2.
An 82 year old man with history of approximately 30 BCC over the last 30 years was referred to our clinic.
This article is protected by copyright. All rights reserved.
http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fjdv.14046
A systematic review examining factors influencing health related quality of life among melanoma cancer survivors
Source:European Journal of Cancer, Volume 69
Author(s): Jean-Francois Hamel, Madeline Pe, Corneel Coens, Francesca Martinelli, Alexander M.M. Eggermont, Yvonne Brandberg, Andrew Bottomley
Eighty percent of melanomas are diagnosed at a localised stage, when they are highly curable. Their survival rate induces long follow-up periods, transforming melanoma into a chronic disease and patients' health-related quality of life (HRQoL). Understanding which patient characteristics are associated with poor HRQoL should allow a more personalised management of their HRQoL. Hence, we propose a systematic review for this purpose.Systematic literature searches were performed in three different electronic databases: PubMed, Web of Science and the Cochrane Library. Only studies published in English after 2005 until June 2016 and exploring HRQoL over a period of at least one year were considered.10 articles were identified from seven different studies, representing a total of 4246 patients. All were observational: six were cross-sectional and only one was prospective. Several patient characteristics associated with HRQoL were identified. Women tend to have lower psychological HRQoL than men. Age was generally associated with variations in HRQoL levels, but there was no consistency across studies. Positive associations between marital status or social interactions and psychological subscales were highlighted by a few studies. Finally, the stage related severity of prognosis at initial diagnosis was systematically associated with worse HRQoL levels (either psychological, physical or global).Several patient characteristics could be identified in melanoma studies that were associated with HRQoL levels. However, these relations were not consistent across studies. Such findings highlight the current lack of empirical data available. Further evidence is needed on HRQoL factors in melanoma survivors.
http://ift.tt/2eYFcoY
Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage
Source:Free Radical Biology and Medicine
Author(s): Seok-Jo Kim, Paul Cheresh, Renea P Jablonski, Luisa Morales-Nebreda, Yuan Cheng, Erin Hogan, Anjana Yeldandi, Monica Chi, Raul Piseaux, Karen Ridge, C. Michael Hart, Navdeep Chandel, GR Scott Budinger, David W Kamp
RationaleAlveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung.ObjectiveTo determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis.MethodsCrocidolite asbestos (100µg/50µl), TiO2 (negative control), bleomycin (0.025 units/50µl), or PBS was instilled intratracheally in 8–10 week-old wild-type (WT - C57Bl/6J) or MCAT mice. The lungs were harvested at 21d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3) / Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay.ResultsCompared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced.ConclusionsOur finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role for AEC mitochondrial H2O2-induced mtDNA damage in promoting lung fibrosis. We reason that strategies aimed at limiting AEC mtDNA damage arising from excess mitochondrial H2O2 production may be a novel therapeutic target for mitigating pulmonary fibrosis.
http://ift.tt/2eJfB2c
Gut microbiota modulate host immune cells in cancer development and growth
Source:Free Radical Biology and Medicine
Author(s): Susan E Erdman, Theofilos Poutahidis
Emerging evidence shows that microbe interactions with the host immune system impact diverse aspects of cancer development and treatment. As a result, exciting new opportunities exist for engineering diets and microbe cocktails to lower cancer risks with fewer adverse clinical effects than traditional strategies. Microbe-based therapies may ultimately be used to reinforce host immune balance and extinguish cancer for generations to come.
http://ift.tt/2fHSS9s
In situ visualization of carbonylation and its co-localization with proteins, lipids, DNA and RNA in Caenorhabditis elegans
Publication date: Available online 11 November 2016
Source:Free Radical Biology and Medicine
Author(s): Mira Kuzmic, Hélène Javot, Jean-Marc Bonzom, Catherine Lecomte-Pradines, Miroslav Radman, Jacqueline Garnier-Laplace, Sandrine Frelon
All key biological macromolecules are susceptible to carbonylation – an irreparable oxidative damage with deleterious biological consequences. Carbonyls in proteins, lipids and DNA from cell extracts have been used as a biomarker of oxidative stress and aging, but formation of insoluble aggregates by carbonylated proteins precludes quantification. Since carbonylated proteins correlate with and become a suspected cause of morbidity and mortality in some organisms, there is a need for their accurate quantification and localization. Using appropriate fluorescent probes, we have developed an in situ detection of total proteins, DNA, RNA, lipids and carbonyl groups at the level of the whole organism. In C. elegans, we found that after UV irradiation carbonylation co-localizes mainly with proteins and, to a lesser degree, with DNA, RNA and lipids. The method efficiency was illustrated by carbonylation induction assessment over 5 different UV doses. The procedure enables the monitoring of carbonylation in the nematode C. elegans during stress, aging and disease along its life cycle including the egg stage.
Graphical abstract
http://ift.tt/2eJmjp4
Interfacial Assembly at Silver Nanoparticle Enhances the Antibacterial Efficacy of Nisin
Publication date: Available online 11 November 2016
Source:Free Radical Biology and Medicine
Author(s): Manoranjan Arakha, Sapna M Borah, Mohammed Saleem, Anupam N Jha, Suman Jha
Nisin is a well-recognised antimicrobial peptide (AMP) used in food industry. However, efficacy of the peptide has been compromised due to development of resistance in different bacterial strains. Here, efficacy of the peptide upon assembly at a silver nanoparticle (AgNP) interface has been characterized. To this end, experimental and simulation studies are done to characterize the interfacial assembly of nisin and underlie antibacterial mechanism. Being an AMP, efficacy of an intact nisin is explored against Gram-positive and Gram-negative bacteria, and compared with antibacterial propensity of the interfacially assembled nisin. Antibacterial propensity, upon the assembly, increases against both kinds of bacteria. Interestingly, the growth inhibition studies of the interfacially assembled nisin indicate that the originally nisin resistant Gram-negative bacteria become sensitive to the nanomolar nisin concentrations. Furthermore, reactive oxygen species (ROS) measurements together with confocal microscopy imaging indicate that the increase in interfacial and intracellular ROS production upon the treatment is underling mechanism of enhanced antibacterial propensity of the assembled nisin. Thus, the study observed that the interfacial assembly of nisin at AgNP interface enhances the efficacy of nisin against different spectrum of bacteria, where the intact nisin is largely ineffective for the studied concentrations.
Graphical abstract
http://ift.tt/2eJfzHC
Nitroxide free radicals protect macular carotenoids against chemical destruction (bleaching) during lipid peroxidation
Source:Free Radical Biology and Medicine
Author(s): M. Zareba, J. Widomska, J.M. Burke, W.K. Subczynski
Macular xanthophylls (MXs) lutein and zeaxanthin are dietary carotenoids that are selectively concentrated in the human eye retina, where they are thought to protect against age-related macular degeneration (AMD) by multiple mechanisms, including filtration of phototoxic blue light and quenching of singlet oxygen and triplet states of photosensitizers. These physical protective mechanisms require that MXs be in their intact structure. Here, we investigated the protection of the intact structure of zeaxanthin incorporated into model membranes subjected to oxidative modification by water- and/or membrane-soluble small nitroxide free radicals. Model membranes were formed from saturated, monounsaturated, and polyunsaturated phosphatidylcholines (PCs). Oxidative modification involved autoxidation, iron-mediated, and singlet oxygen-mediated lipid peroxidation. The extent of chemical destruction (bleaching) of zeaxanthin was evaluated from its absorption spectra and compared with the extent of lipid peroxidation evaluated using the thiobarbituric acid assay. Nitroxide free radicals with different polarity (membrane/water partition coefficients) were used. The extent of zeaxanthin bleaching increased with membrane unsaturation and correlated with the rate of PC oxidation. Protection of the intact structure of zeaxanthin by membrane-soluble nitroxides was much stronger than that by water-soluble nitroxides. The combination of zeaxanthin and lipid-soluble nitroxides exerted strong synergistic protection against singlet oxygen-induced lipid peroxidation. The synergistic effect may be explained in terms of protection of the intact zeaxanthin structure by effective scavenging of free radicals by nitroxides, therefore allowing zeaxanthin to quench the primary oxidant, singlet oxygen, effectively by the physical protective mechanism. The redox state of nitroxides was monitored using electron paramagnetic resonance spectroscopy. Both nitroxide free radicals and their reduced form, hydroxylamines, were equally effective. Obtained data were compared with the protective effects of α-tocopherol, which is the natural antioxidant and protector of MXs within the retina. The new strategies employed here to maintain the intact structure of MXs may enhance their protective potential against AMD.
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Sestrin2 inhibits hypoxia-inducible factor-1α accumulation via AMPK-mediated prolyl hydroxylase regulation
Source:Free Radical Biology and Medicine
Author(s): Kyuhwa Seo, Suho Seo, Sung Hwan Ki, Sang Mi Shin
Sestrin2 (SESN2) is an antioxidant protein that modulates cellular redox homeostasis through regeneration of peroxiredoxins. It has beneficial effects in oxidative or metabolic stress conditions as an upstream regulator of AMP-activated protein kinase (AMPK). Since hypoxia causes oxidative and metabolic stress, this study investigated the effect of SESN2 on signaling pathways altered by hypoxia in colon cancer cells. SESN2 overexpression in HEK293 cells inhibited hypoxia-inducible factor-1α (HIF-1α), which plays a crucial role in tumor growth and development in hypoxia. Moreover, infection with adenovirus-SESN2 (Ad-SESN2) decreased hypoxia or CoCl2-induced HIF-1α accumulation in colorectal cancer cells. Ad-SESN2 also reduced CoCl2-induced hypoxia response element (HRE)-luciferase activity and mRNA level of HIF-1α-driven genes. Furthermore, Ad-SESN2 infected cells showed anti-metastatic effects in serum-induced cell migration and invasion in vitro. Ad-SESN2 facilitated the ubiquitination of HIF-1α protein and increased hydroxyl-HIF-1α (OH-HIF-1α) level. In contrast, treatment with dimethyloxalylglycine (DMOG), an inhibitor of prolyl hydroxylase (PHD), reversed Ad-SESN2-induced OH-HIF-1α and subsequently suppressed HIF-1α level. The inhibitory effects of SESN2 on the serum-induced in vitro cell migration and invasion were also abrogated by DMOG treatment. Furthermore, knockdown of AMPKα reversed Ad-SESN2-mediated increase of OH-HIF-1α and inhibition of HIF-1α. Dominant-negative form of AMPK also restored the Ad-SESN2 mediated decrease in HIF-1α accumulation. Lastly, Ad-SESN2 suppressed tumor growth in a mouse xenograft model. Taken together, these results suggest that SESN2 increases degradation of HIF-1α via AMPK-PHD regulation that contributes to inhibition of in vitro and in vivo tumorigenesis.
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Connexin43 regulates high glucose-induced expression of fibronectin, ICAM-1 and TGF-β1 via Nrf2/ARE pathway in glomerular mesangial cells
Publication date: Available online 11 November 2016
Source:Free Radical Biology and Medicine
Author(s): Zhiquan Chen, Xi Xie, Junying Huang, Wenyan Gong, Xiaoyu Zhu, Qiuhong Chen, Jiani Huang, Heqing Huang
Nrf2/ARE signaling pathway is a crucial cellular defense system to cope with oxidative stress, which is adaptively activated, in diabetic condition that is not efficient enough to resist the oxidative stress provoked by hyperglycemia. We have previously demonstrated that Connexin43 (Cx43) attenuates renal fibrosis through c-Src. However, the underlying mechanisms need to be further clarified. It has been reported that Cx43 possesses the ability of anti-oxidative. The current study aimed to determine if Cx43 exerts protective effects on renal fibrosis in diabetes via activation of Nrf2/ARE pathway and explore the underlying molecular mechanisms. The following findings were observed: (1) Cx43 expression decreased and c-Src activity increased in kidneys of diabetic animals; (2) Over-expressed Cx43 in high glucose treated GMCs inhibited protein levels of FN, ICAM-1 and TGF-β1; (3) Nrf2/ARE signaling adaptively responded to high glucose treatment in GMCs; (4) Cx43 reduced ROS generation by boost Nrf2/ARE signaling under high glucose condition; (5) Inhibition of c-Src activity promoted nucleus accumulation of Nrf2; (6) Over-expressed Cx43 inhibited c-Src activity and the interaction between c-Src and Nrf2 in GMCs cultured in high glucose. Thus we propose that Cx43 might enhance the activation of Nrf2/ARE pathway by means of inhibiting c-Src activity to hinder the nuclear export of Nrf2, and then reduce expression of FN, ICAM-1 and TGF-β1, ultimately attenuating renal fibrosis in diabetes.
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