Head and Neck Diseases by Alexandros G.Sfakianakis: 11/04/16

Παρασκευή 4 Νοεμβρίου 2016

Health-related quality of life 10 years after oesophageal cancer surgery

Publication date: December 2016
Source:European Journal of Cancer, Volume 69
Author(s): Anna Schandl, Jesper Lagergren, Asif Johar, Pernilla Lagergren
PurposeTo determine whether oesophageal cancer survivors recover in health-related quality of life (HRQOL) within 10 years of surgery.MethodsA prospective, nationwide, population-based cohort study including 90% of all oesophageal cancer surgery patients in Sweden in 2001–2005, with follow-up through 2015. HRQOL was assessed 5 and 10 years postoperatively, using questionnaires for cancer in general (EORTC QLQ-C30) and oesophageal cancer specifically (EORTC QLQ-OES18). The HRQOL measures at 10 years after surgery were compared with the 5-year assessment. The 10-year HRQOL scores were compared with a population-based reference population (4910 individuals), individually matched for age, sex and comorbidity, by means of mean score differences with 95% confidence intervals.ResultsAmong 616 patients, 104 (17%) survived at least 10 years. Of these, 92 (88%) responded to the HRQOL questionnaires at 5 and 10 years after surgery. Among the responders, 71% were older than 70 years. Patients did not improve in HRQOL between 5 and 10 years. Instead, the scores for 23 out of 25 HRQOL aspects declined, with clinically relevant and statistically significant deterioration in role function and appetite loss. Compared to the reference population, the 10 year-survivors had worse scores in all 25 HRQOL aspects, with significant deterioration in global quality of life, role functioning, social functioning and most symptoms. The most severe problems compared to the reference population were reflux, eating difficulties, diarrhoea and appetite loss.ConclusionPatients who have undergone curative treatment for oesophageal cancer experience reduced HRQOL with persisting symptoms 10 years after surgery.

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Diet, body size, physical activity and risk of prostate cancer: An umbrella review of the evidence

Publication date: December 2016
Source:European Journal of Cancer, Volume 69
Author(s): Georgios Markozannes, Ioanna Tzoulaki, Dimitra Karli, Evangelos Evangelou, Evangelia Ntzani, Marc J. Gunter, Teresa Norat, John P. Ioannidis, Konstantinos K. Tsilidis
The existing literature on the relationship between diet, body size, physical activity and prostate cancer risk was summarised by the World Cancer Research Fund Continuous Update Project (CUP). An evaluation of the robustness of this evidence is required to help inform public health policy. The robustness of this evidence was evaluated using several criteria addressing evidence strength and validity, including the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, number of prostate cancer cases, between-study heterogeneity, 95% prediction intervals, small-study effects bias, excess significance bias and sensitivity analyses with credibility ceilings. A total of 248 meta-analyses were extracted from the CUP, which studied associations of 23 foods, 31 nutrients, eight indices of body size and three indices of physical activity with risk of total prostate cancer development, mortality or cancer development by stage and grade. Of the 176 meta-analyses using a continuous scale to measure the exposures, no association presented strong evidence by satisfying all the aforementioned criteria. Only the association of height with total prostate cancer incidence and mortality presented highly suggestive evidence with a 4% higher risk per 5 cm greater height (95% confidence interval, 1.03, 1.05). Associations for body mass index, weight, height, dietary calcium and spirits intake were supported by suggestive evidence. Overall, the association of diet, body size, physical activity and prostate cancer has been extensively studied, but no association was graded with strong evidence.

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Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation

Publication date: Available online 4 November 2016
Source:European Journal of Cancer
Author(s): David Miles, David Cameron, Igor Bondarenko, Lyudmila Manzyuk, Juan Carlos Alcedo, Roberto Ivan Lopez, Seock-Ah Im, Jean-Luc Canon, Yaroslav Shparyk, Denise A. Yardley, Norikazu Masuda, Jungsil Ro, Neelima Denduluri, Stanislas Hubeaux, Cheng Quah, Carlos Bais, Joyce O'Shaughnessy
AimMERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC).MethodsIn this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m² on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations.ResultsOf 481 patients randomised (242 placebo–paclitaxel; 239 bevacizumab–paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51–0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo–paclitaxel versus 11.0 months with bevacizumab–paclitaxel) and 0.64 (96% confidence interval, 0.47–0.88; log-rank p = 0.0038) in the pVEGF-Ahigh subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%).ConclusionThe significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab.Clinical trials registrationClinicalTrials.gov NCT01663727.

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Functional and Genomic Architecture of Borrelia burgdorferi-Induced Cytokine Responses in Humans

Publication date: Available online 3 November 2016
Source:Cell Host & Microbe
Author(s): Marije Oosting, Mariska Kerstholt, Rob ter Horst, Yang Li, Patrick Deelen, Sanne Smeekens, Martin Jaeger, Ekta Lachmandas, Hedwig Vrijmoeth, Mihaela Lupse, Mirela Flonta, Robert A. Cramer, Bart Jan Kullberg, Vinod Kumar, Ramnik Xavier, Cisca Wijmenga, Mihai G. Netea, Leo A.B. Joosten
Despite the importance of immune variation for the symptoms and outcome of Lyme disease, the factors influencing cytokine production during infection with the causal pathogen Borrelia burgdorferi remain poorly understood. Borrelia infection-induced monocyte- and T cell-derived cytokines were profiled in peripheral blood from two healthy human cohorts of Western Europeans from the Human Functional Genomics Project. Both non-genetic and genetic host factors were found to influence Borrelia-induced cytokine responses. Age strongly impaired IL-22 responses, and genetic studies identified several independent QTLs that impact Borrelia-induced cytokine production. Genetic, transcriptomic, and functional validation studies revealed an important role for HIF-1α-mediated glycolysis in the cytokine response to Borrelia. HIF-1α pathway activation and increase in glycolysis-derived lactate was confirmed in Lyme disease patients. In conclusion, functional genomics approaches reveal the architecture of cytokine production induced by Borrelia infection of human primary leukocytes and suggest a connection between cellular glucose metabolism and Borrelia-induced cytokine production.

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Cytokine-mediated processes regulate both host defense and long-term inflammatory complications in Lyme disease caused by Borrelia burgdorferi. Oosting et al. use functional genomics to reveal the architecture of cytokine production during Borrelia infection of human primary leukocytes. Their data suggest a connection between cellular glucose metabolism and Borrelia-induced cytokine production.

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High Sucrose Intake during Gestation Increases Angiotensin II Type 1 Receptor-Mediated Vascular Contractility Associated with Epigenetic Alterations in Aged Offspring Rats

Publication date: Available online 3 November 2016
Source:Peptides
Author(s): Lei Wu, Aiping Shi, Di Zhu, Le Bo, Yuan Zhong, Juan Wang, Zhice Xu, Caiping Mao
Accruing evidence have confirmed that the fetal programming in response to adverse environmental in utero factors plays essential roles in the pathogenesis of hypertension in later life. High sugar intake has been accepted worldwide in everyday life diet and becomes the critical public health issue. Our previous studies indicated that intake of high sucrose (HS) during pregnancy could change the vascular reactivity and dipsogenic behavior closely associated with abnormal renin-angiotensin system (RAS), to increase the risk of hypertension in adult offspring. In the present study, we tested the hypothesis that maternal HS intake in pregnancy may further deteriorate the Ang II-induced cardiovascular responses in the aged offspring. HS intake was provided to pregnant rats throughout the gestation. Blood pressure (BP) in conscious state and vascular contractility in vitro were measured in 22-month-old aged offspring rats. In addition, mRNA and protein expressions and epigenetic changes of Ang II type 1 receptor (AT1R) gene in blood vessels were determined with the methods of real-time RT-PCR, Western blotting, and Chromatin Immunoprecipitation Assay (CHIP). Results showed that, in the aged offspring, maternal HS intake during gestation would cause the elevation of basal BP which could be diminished by losartan. Although the circulatory Ang II was not changed, levels of local Ang II were significantly increased in blood vessels. In addition, prenatal HS exposure would significantly enhance the AT1R-mediated vasoconstrictions in both aorta and mesenteric arteries of the aged offspring. Moreover, in the aged offspring of prenatal HS exposure, mRNA and protein expressions of AT1R gene in both large and small blood vessels were significantly increased, which should be closely associated with the changes of epigenetic mechanisms such as histone modifications. Collectively, we proposed that maternal HS intake during gestation would cause abnormal BP responses mediated via the enhancement of vascular RAS, together with the increased expression of AT1R gene related to the its epigenetic changes, which would actually lead to the overt phenotype of hypertension in the aged offspring.

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Plasmin is a natural trigger for bradykinin production in patients with hereditary angioedema with factor XII mutations

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Steven de Maat, Jenny Björkqvist, Chiara Suffritti, Chantal P. Wiesenekker, Willem Nagtegaal, Arnold Koekman, Sanne van Dooremalen, Gerard Pasterkamp, Philip G. de Groot, Marco Cicardi, Thomas Renné, Coen Maas
BackgroundPatients with angioedema experience unpredictable attacks of tissue swelling in which bradykinin is implicated. Several distinct mutations in Factor XII (FXII) are associated with hereditary angioedema (HAE) in the presence of normal C1 esterase inhibitor activity (FXII-HAE). The underlying disease mechanisms are unclear, which complicates diagnosis and treatment.ObjectiveWe sought to identify the natural trigger for FXII activation, which causes uncontrolled bradykinin production in patients with FXII-HAE.MethodsWe generated recombinant variants of FXII, representing health and disease, and studied their behavior in functional studies. We investigated bradykinin-forming pathways in blood plasma with newly developed nanobody-based analytic methods.ResultsWe here report that FXII-HAE mutations collectively introduce new sites that are sensitive to enzymatic cleavage by plasmin. These FXII mutants rapidly activate after cleavage by plasmin, escape from inhibition through C1 esterase inhibitor, and elicit excessive bradykinin formation. Furthermore, our findings indicate that plasmin modulates disease activity in patients with FXII-HAE. Finally, we show that soluble lysine analogs attenuate this mechanism, explaining their therapeutic value in patients with HAE.ConclusionOur findings indicate a new pathway for bradykinin formation in patients with HAE, in which FXII is cleaved and activated by plasmin. This should lead to the identification of new markers for diagnosis and targets for treatment.

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Brief Overview of This Month's JACI

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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Editorial Board

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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Information for Readers

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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News & Notes

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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Cover 1

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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CME Activities Calendar

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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News Beyond Our Pages

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Marc E. Rothenberg, Jean Bousquet

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Immune modules shared by innate lymphoid cells and T cells

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Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Michelle L. Robinette, Marco Colonna
In recent years, innate lymphoid cells (ILCs) have emerged as innate correlates to T cells. The similarities between ILCs and T cells indicate that lymphocytes of fundamentally distinct lineages can share core "immune modules" that encompass transcriptional circuitry and effector functions while using nonredundant complementary mechanisms of pattern recognition to enact these functions. We review modules currently recognized to be shared between ILCs and T cells.

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Immune modules shared by innate lymphoid cells and T cells

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5

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Innate lymphoid cells in allergic and nonallergic inflammation

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Hideaki Morita, Kazuyo Moro, Shigeo Koyasu
In the last decade, the full picture of the role of innate lymphoid cells (ILCs) has been gradually revealed. ILCs are classified into 3 groups based on their transcription factors and cytokine production patterns, which mirror helper T-cell subsets. Unlike T cells and B cells, ILCs do not have antigen receptors. They promptly respond to multiple tissue-derived factors, such as cytokines and alarmins, and produce multiple proinflammatory and immunoregulatory cytokines. It has been reported that ILC-derived cytokines are important for the induction and regulation of inflammation. Accumulating evidence suggests that ILCs play substantial roles in protection against infection and the pathogenesis of inflammatory diseases, such as allergic diseases and autoimmune diseases. Different ILC subsets localize in distinct tissue/organ niches and receive tissue-derived signals on different types of inflammation, which allows them to acquire diverse phenotypes with specialized effector capacities. In this review we highlight the roles of ILCs in a variety of organs, such as the airway, skin, and gastrointestinal tract, in the context of allergic and nonallergic inflammation.

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Advances in rhinitis and rhinosinusitis in 2015

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Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Claus Bachert, Elien Gevaert
The last year has seen great progress in the understanding of upper airway disease and in its management. For allergic rhinitis, authors focused on the prediction of and effect on the natural course of disease. New evidence was published for the disease-modifying effect of allergen immunotherapy in terms of avoidance of new sensitizations and prevention of asthma in either randomized or real-life studies. Specifically, for patients with house dust mite allergies, which are often underestimated and difficult to diagnose, the efficacy of SQ house dust mite sublingual immunotherapy tablets has been demonstrated in patients with allergic rhinitis and asthma. For the first time, allergen immunotherapy significantly reduced asthma exacerbations. In patients with chronic rhinosinusitis, a novel endotyping approach purely based on T helper cell biomarkers has been developed and has shown clinical relevance through associations with asthma comorbidity and recurrence after surgery. Severe nasal polyposis with high risk for asthma comorbidity and disease recurrence is characterized by type 2 inflammatory patterns, including IgE antibodies to staphylococcal superantigens; several studies using biologic agents have targeted exactly this spectrum of mediators. This goes in parallel with new knowledge on even more type 2 mediators derived from epithelial cells, which will expand the number of possible candidates for innovative intervention.

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Advances in allergen immunotherapy in 2015

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Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Robert K. Bush
The year 2015 saw a significant number of advances in allergen immunotherapy (AIT), and several of these are reviewed in this report. Although AIT has been used for more than 100 years, investigations into optimal treatment approaches and mechanisms are ongoing. Among the highlights was a report by an international group of experts who reviewed AIT guidelines from the major specialty societies and addressed potential unmet needs. Herein, advances in the effectiveness, safety, and mechanisms of sublingual and oral immunotherapy are reviewed. Development of hypoallergenic vaccines to enhance safety, newer routes and regimens to improve efficacy, and biomarkers to monitor immunotherapy are also discussed.

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The Editors' Choice

Publication date: November 2016
Source:Journal of Allergy and Clinical Immunology, Volume 138, Issue 5
Author(s): Cezmi A. Akdis, Zuhair K. Ballas

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Resolution of left ventricular postinfarction thrombi in patients undergoing percutaneous coronary intervention using rivaroxaban in addition to dual antiplatelet therapy

Constantinos Andreas Makrides Oct 26, 2016; 2016:201621784-201621784 case-report

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Coexisting pulmonary haemorrhage and venous thrombosis: a tricky but novel case

Alexandra Fielding, Mira Pecheva, Aser Farghal, Russell Phillips Oct 20, 2016; 2016:201621716-201621716 case-report

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Native valve Proteus mirabilis endocarditis: successful treatment of a rare entity formulated by in vitro synergy antibiotic testing

Caroline R Brotzki, Kari A Mergenhagen, Zackery P Bulman, Brian T Tsuji, Charles S Berenson Oct 20, 2016; 2016:201621595-201621595 case-report

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Role of diagnostic laparoscopy in penetrating anterior abdominal wall trauma

David Parizh, Vadim Meytes, Anthony Kopatsis Oct 14, 2016; 2016:201621764-201621764 case-report

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Ascites: it is not all alcohol--a case of constrictive pericarditis

Asgher Champsi, Muzzammil Ali Oct 8, 2016; 2016:201621502-201621502 case-report

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Bleeding manifestations in a patient with amyloidosis

Luai Alhazmi, Abdulelah Nuqali, Ragheb Assaly Oct 8, 2016; 2016:201621694-201621694 case-report

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Severe hypercalcaemia in a child secondary to use of alternative therapies

Catriona Boyd, Abdul Moodambail Oct 6, 2016; 2016:201621584-201621584 case-report

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Aortic valve replacement for Libman-Sacks endocarditis

Jack B Keenan, Rajesh Janardhanan, Brandon T Larsen, Zain Khalpey Oct 4, 2016; 2016:201621591-201621591 case-report

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Immune-mediated Disease in Ipilimumab Immunotherapy of Melanoma with FDG PET-CT

Publication date: Available online 4 November 2016
Source:Academic Radiology
Author(s): Jason W. Wachsmann, Ramapriya Ganti, Fangyu Peng
Rationale and ObjectivesThe purposes of this study were to provide a case-based overview of various immune-mediated side effects detected by 18F-Fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) in the patients receiving ipilimumab immunotherapy for treatment of malignant melanoma, and discuss the importance of recognizing immune-mediated side effects in the use of F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on metastatic melanoma.Materials and MethodsThis is a retrospective case series study of the patients diagnosed with melanoma who were subjected to immunomodulating therapy with ipilimumab. F-18 FDG PET-CT findings were reviewed, and the patients with immune-mediated side effects were selected for further analysis, in conjunction with review of clinical progress notes, the results of laboratory tests, and findings of other imaging tests.ResultsFour patients with immune-mediated side effects were identified among the patients being treated with ipilimumab and subjected to F-18 FDG PET-CT for monitoring therapeutic effects. These immune mediated side effects include new findings of abnormal increased FDG uptake associated with immune-mediated pancreatitis and hypophysitis, as well as immune-mediated thyroiditis and colitis reported previously.ConclusionsVarious immune-mediated side effects were detected by F-18 FDG PET-CT in the patients subjected to immunomodulating therapy with ipilimumab. It is essential for the interpreting provider to recognize and differentiate abnormal FDG uptake associated with immune-mediated side effects from hypermetabolic malignant lesions when using F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on melanoma lesions.

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Are diet diaries of value in recording dietary intake of sugars? A retrospective analysis of completion rates and information quality

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Παρασκευή 4 Νοεμβρίου 2016

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