Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity

Abstract

Introduction

Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN.

Materials and methods

We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density. A retrospective study was carried out on patients with colorectal cancer who had received oxaliplatin-based chemotherapy. DNA for KCNN3 genotyping was extracted from leukocytes. The region containing the CAG repeats was amplified by PCR and the products separated by capillary electrophoresis for length analysis. The patients were divided into three groups depending on whether they carried two short alleles, one short allele and one long allele, or two long alleles. The primary endpoint was the onset of grade 2 or 3 neuropathy to oxaliplatin.

Results

There was no difference in current density, but oxaliplatin induced a differential effect on apamin-sensitive current density between the two isoforms expressed in the HEK cell lines. There was a significant reduction of store-operated calcium entry into cells expressing the short and more active isoform only after high concentration of oxaliplatin exposition. Eighty-six patients were included in the clinical study. There was no significant association between OIN and KCNN3 polymorphism for the three groups.

Conclusion

We observed a slight association between OIN and CAG repeat polymorphisms of the KCNN3 gene in a preclinical model, but not a clinical study.

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Heterogeneity in Positive Predictive Value of RAS Mutations in Cytologically Indeterminate Thyroid Nodules

Thyroid, Ahead of Print.


https://ift.tt/2k4QIDx

Identification of a Recurrent LMO7–BRAF Fusion in Papillary Thyroid Carcinoma

Thyroid, Ahead of Print.


https://ift.tt/2rNkOyF

Predominantly cystic clear cell renal cell carcinoma and multilocular cystic renal neoplasm of low malignant potential form a low-grade spectrum

Abstract

Multilocular cystic renal cell carcinoma has been recently excluded from clear cell renal cell carcinoma (CCRCC) category and re-designated as multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) due to its uniformly good outcomes. While strict distinction between MCRNLMP from predominantly cystic CCRCC (pc-CCRCC) is being emphasized, the significance of extensive true cystic component in CCRCC has not been investigated. Herein, we analyzed 57 MCRNLMP, 69 pc-CCRCC, and 46 non-cystic CCRCC. There were no statistically significant differences between the three subtypes in age, gender, and laterality. ISUP grades were 1 (73%) or 2 (27%) for MCRNLMP; for pc-CCRCC were 1 (31%), 2 (60%), and 3 (9%); and for non-cystic CCRCC were 1 (9%), 2 (52%), 3 (26%), and 4 (13%). MCRNLMP were either pT stage 1 (91%) or 2 (9%), pT stages for pc-CCRCC were 1 (92.5%), 2 (1.5%), and 3 (6%) and for non-cystic CCRCC were 1 (58.7%), 2 (6.5%), and 3 (34.8%). None of MCRNLMP patients developed recurrences or metastases, and only 1 contralateral kidney tumor and 1 metastasis developed in pc-CCRCC. In contrast, 19 patients with non-cystic CCRCC developed metastases (5-year PFS 58%, CI 38.3–73.5%), and 1 patient died of disease. Monosomy 3 was common in both MCRNLMP (3/3) and pc-CCRCC (6/7). This large series of MCRNLMP confirms its indolent behavior, shows that pc-CCRCC has significantly better prognosis than non-cystic CCRCC and may define the lower grade spectrum of CCRCC. We recommend that the presence and extent of CCRCC cystic component should be documented in the pathology report.

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Allergen‐specific immunotherapy induces regulatory T cells in an atopic dermatitis mouse model

Allergy, EarlyView.


https://onlinelibrary.wiley.com/doi/abs/10.1111/all.13465?af=R

Incidence of pediatric atopic dermatitis following thymectomy: A Danish register study

Allergy, EarlyView.


https://onlinelibrary.wiley.com/doi/abs/10.1111/all.13457?af=R

A Commentary on: “Effects of Regular Physical Activity on the Cognitive Performance of Type 2 Diabetic Patients: A systematic Review” by Podolski et al. (Metab Syndr Relat Disord 2017;15:481–493)

Metabolic Syndrome and Related Disorders, Ahead of Print.


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Out of my league: Appraisals of anxiety and confidence in others by individuals with and without social anxiety disorder

Publication date: Available online 16 May 2018
Source:Journal of Anxiety Disorders
Author(s): Tatiana Bielak, David A. Moscovitch, Stephanie Waechter
Forty participants with social anxiety disorder (SAD) and 42 healthy controls (HCs) were randomized to watch a confederate deliver a speech in either a visibly anxious or confident manner. Participants rated their perception of the presenter's desirability across five attributes and compared themselves to the presenter along these same dimensions. Participants then delivered their own speeches, and were rated in a similar manner by trained research assistants who were naïve to participants' group status and study objectives. Results demonstrated that all participants, irrespective of group status, judged the visibly anxious presenter as being less desirable and the confident presenter as more desirable. Socially anxious participants tended to view themselves as inferior to confident others. Coders also rated participants with SAD, based on their speeches, as being less interpersonally desirable than HCs. These results suggest that individuals who appear visibly anxious may be objectively disadvantaged in their ability to make a positive first impression on others. We discuss these findings in relation to theoretical models of social anxiety and explore how to address such interpersonal factors in psychological interventions for SAD.



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Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust

AbstractGlobally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale.Implications for Practice.Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars can contribute to cancer care will depend on their level of acceptance by health care systems, health care professionals, and patients. A better understanding of the regulatory basis for the approval of biosimilars may enhance confidence and trust in these agents. In order to have informed discussions about treatment choices with their patients, oncologists should familiarize themselves with the biosimilar paradigm.

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Phase II Study of Irinotecan Plus Panitumumab as Second‐Line Therapy for Patients with Advanced Esophageal Adenocarcinoma

AbstractLesson Learned. Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma.Background.Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second‐line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second‐line therapy for advanced EAC.Methods.The primary endpoint was response rate (RR). Patients with one prior treatment were given Pa 9 mg/m2 on day 1 and Ir 125 mg/m2 on days 1 and 8 of each 21‐day cycle. Inclusion criteria were confirmed EAC, measurable disease, no prior Ir or Pa, performance status <2, and normal organ function.Results.Twenty‐four patients were enrolled; 18 were eligible and evaluable. These patients were all white, with a median age of 62.5 years (range, 33–79 years), and included 15 men and 3 women. The median number of cycles was 3.5. The most common grade 1–2 adverse events were fatigue, diarrhea, anemia, leukopenia, and hypoalbuminemia. Grade 3–4 adverse events included hematologic, gastrointestinal, electrolyte, rash, fatigue, and weight loss. The median follow‐up was 7.2 months (range, 2.3–14 months). There were no complete remissions. The partial response rate was 6% (1/18; 95% confidence interval [CI], 0.01–0.26). The clinical benefit (partial response [PR] plus stable disease [SD]) rate was 50%. The median overall survival was 7.2 months (95% CI, 4.1–8.9) with an 11.1% 1‐year survival rate. The median progression‐free survival was 2.9 months (95% CI, 1.6–5.3).Conclusion.Irinotecan and panitumumab as second‐line treatment for advanced EAC are not active.

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Meta‐Research on Oncology Trials: A Toolkit for Researchers with Limited Resources

Abstract"Meta‐research" is a discipline that investigates research practices. Meta‐research on clinical trials is an attempt to summarize descriptive and methodological features of published or ongoing clinical trials, including aspects of their implementation, design, analysis, reporting, and interpretation. In this type of investigation, the unit of analysis is a primary source of information about a clinical trial (e.g., published reports, study protocols, or abstracts), with meta‐research being a second layer of information that summarizes what is known from various primary sources. After the formulation of the primary research question, the methodology of meta‐research resembles that of other research projects, with predefined eligibility criteria, exposure variables, primary and secondary outcomes of interest, and an analysis plan. This type of study usually provides a high‐level picture of the literature on a specific topic, always accompanied by a critical evaluation of the methodology and/or the quality of reporting of the studies included. Because relatively few resources are consumed to produce meta‐research, these studies offer a great opportunity for clinical scientists working in settings with limited resources. In this article, we present the principles of designing and conducting meta‐research and use our experience to suggest recommendations on how to perform and how to report this type of potentially very creative study.Implications for Practice.The term meta‐research pertains to a type of study in which the unit of analysis is, in most cases, the publication of a clinical trial. This type of study usually provides a high‐level picture of the literature on a specific topic, always accompanied by a critical evaluation of the methodology, design, and/or the quality of reporting of the studies included. Because relatively few resources are consumed to produce meta‐research, these studies offer a great opportunity for clinical scientists who work in low‐income countries. This article presents the principles of designing and conducting meta‐research and proposes practical recommendations on how to perform and report this type of potentially very creative study.

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Incidence of Thyroid Function Test Abnormalities in Patients Receiving Immune‐Checkpoint Inhibitors for Cancer Treatment

AbstractBackground.With the advent of immune‐checkpoint inhibitor (ICI) therapy (anti‐CTLA‐4, anti‐PD‐1), immune‐related adverse events such as thyroid function test abnormalities (TFTAs) are common, with a reported incidence range of 2%–15% depending upon the ICI used. The aim of this study is to describe the incidence of TFTAs retrospectively in patients who received ICI therapy.Methods.A total of 285 patients were reviewed (178 male, 107 female; 16–94 years of age), of whom 218 had no baseline TFTAs, 61 had baseline TFTAs, and 6 had a history of thyroidectomy (excluded). At least one dose of ipilimumab and/or nivolumab or pembrolizumab was administered. Post‐ICI therapy TFTAs were classified according to standard definitions of thyroid conditions when possible.Results.A total of 35% (76/218) patients had new‐onset TFTAs on ICI therapy. Of note, 70.5% (43/61) had baseline TFTAs that were exacerbated by ICI therapy. The median times to new‐onset or exacerbated baseline TFTA were 46 and 33 days, respectively. Of note, 64.5% (20/31) of patients on both ipilimumab and nivolumab had new‐onset TFTAs, compared with 31.3% (15/48) on ipilimumab, 31.5% (28/89) on nivolumab, and 26% (13/50) on pembrolizumab.Conclusion.The incidence of TFTAs with ICI therapy was higher than previously reported. Patients with baseline TFTAs and/or who were receiving ipilimumab and nivolumab combination therapy had a higher incidence of TFTAs than patients receiving single‐agent ICI therapy. We recommend more frequent evaluation of thyroid function in the first 8 weeks, especially in patients with baseline TFTAs.Implications for Practice.Increased use of immune‐checkpoint inhibitors in cancer treatment has highlighted the importance of monitoring for and treating immune‐related adverse events. This study was conducted to assess the incidence of thyroid function test abnormalities retrospectively in patients with cancer on immune‐checkpoint inhibitors, which is not known exactly. This study is unique in that it included patients with a variety of histologic subtypes of cancer and also followed the clinical course of patients with baseline thyroid function test abnormalities. This study can help make oncologists aware that the incidence of thyroid function test abnormalities is higher than anticipated. Early identification and timely treatment can help ameliorate symptoms for patients and improve their overall quality of life.

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Personalized Symptom Goals and Patient Global Impression on Clinical Changes in Advanced Cancer Patients

AbstractBackground.The aim of this study was to assess the patients' global impression (PGI) after symptom management, as well as the achievement of personalized symptom goals (PSG). The secondary outcome was to assess related factors.Subjects, Materials, and Methods. Advanced cancer patients admitted to palliative care units rated symptom intensity by using the Edmonton Symptom Assessment Score (ESAS) at admission and then after 1 week. For each symptom, patient‐reported PGI and PSG, as well as the rate of PSG response, were evaluated.Results.Eight hundred seventy‐six patients were taken into consideration for this study. A mean of 1.71–2.16 points was necessary to perceive a bit better improvement of symptom intensity. Most patients had a PSG of ≤3. A statistically significant number of patients achieved their PSG after starting palliative care. Patients with high intensity of ESAS items at admission achieved a more favorable PGI response. In the multivariate analysis, symptom intensity and PSG were the most frequent factors independently associated to a best PGI, whereas high levels of Karnofsky had a lower odd ratio.Conclusion.PSG and PGI seem to be relevant for patients' assessment and decision‐making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response.Implications for Practice.Personalized symptom goals and global impression of change are relevant for patients' assessment and decision‐making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response.

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The clinical significance of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in gastric cancer: A systematic review and meta-analysis

Publication date: July 2018
Source:Critical Reviews in Oncology/Hematology, Volume 127
Author(s): Hai Qian, Kwaku Appiah-Kubi, Ying Wang, Min Wu, Yan Tao, Yan Wu, Yongchang Chen
BackgroundThe overexpression and mutation of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are widespread in cancers and have been recognized as attractive oncologic targets with diverse therapeutic targets. Reports of the overexpression of genes, proteins and mutations of PDGFs/PDGFRs in gastric cancer and their associations with clinicopathological features, Western and Asian patients, as well as prognostic role have shown variable outcomes. This study sought to employ meta-analysis to evaluate PDGFs/PDGFRs status prognostic significance and their association with clinicopathological features of gastric cancer.MethodA comprehensive search of PubMed database for studies that investigated the overexpression of mRNA/Protein and mutation of PDGFs/PDGFRs in gastric cancer of Western and Asian patients, their prognostic significance and association with clinicopathological characteristics in May, 2017 or earlier was carried out by two reviewers independently. Pooled odd ratios and hazard ratios at 95% confidence intervals were estimated and summarized using fixed-effect and random-effect Mantel-Haenszel models and Inverse Variance models in Review Manager software version 5.3.ResultsFourteen studies with 16 datasets of 1178 patients were included in meta-analysis. Fourteen studies of 1178 patients with 1446 cases and 7 studies of 1076 patients with 1280 cases were included in meta-analysis of clinicopathological and prognostic significance of high or positive PDGF/PDGFR status respectively. Odd ratio at 95% confidence intervals for different groups of analysis are as follows: males versus females(OR = 1.38, 95% CI: 1.04–1.83, POR = 0.03); ≥T2 stage versus T1 stage(OR = 2.06, 95% CI: 1.22–3.49, POR = 0.007); nodal metastasis versus no nodal metastasis(OR = 2.78, 95% CI: 1.48–5.22, POR = 0.002); TNM stage ≥II versus TNM stage I(OR = 3.55, 95% CI: 1.89–6.69, POR<0.0001). Subgroup analysis of the association of PDGF/PDGFR among Western patients(OR = 0.24 95% CI: 0.10–0.58, POR = 0.002) and association of PDGFs/PDGFRs gene mutation among gastric cancer patients(OR = 0.15, 95% CI: 0.05–0.45, POR = 0.0008) were significant. The association of PDGFs/PDGFRs in young and middle age versus elderly aged, undifferentiated versus well differentiated tumors, large tumor size group(>6 cm) versus small tumor size group(≤6 cm) were insignificant. Subgroup analysis of the association of PDGFs/PDGFRs among Western Asian patients; PDGF/PDGFR mRNA expression and protein expression among gastric cancer patients were insignificant. In addition, PDGF/PDGFR status among gastric cancer patients was insignificant in overall effect analysis PDGF/PDGFR status has shown to predict reduced overall survival(HR = 1.25, 95% CI: 0.49–3.22, PHR = 0.64) and relapse free survival(HR = 0.93, 95% CI: 0.36–2.41, PHR = 0.88) insignificantly. Also, overall prognostic effect analysis(HR = 1.07, 95% CI: 0.58–1.96, PHR = 0.84) was insignificant.ConclusionPDGFs/PDGFRs status amongst gastric cancer patients plays a key role in clinical variables and nodal metastasis. These insights might be helpful in providing guidelines for diagnosis, molecular target therapy, and prognosis of gastric cancer.



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33. SNP microarray autozygosity-directed mutation assessment of children and families with heritable retinal dystrophies in Costa Rica; identification of autosomal recessive mutations and one copy number variant

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Daynna J. Wolff, Iya Znoyko, W. Bailey Glen, Joaquin Martinez Arguedas, Rames Badilla Porras, Mae Millicent Peterseim




https://ift.tt/2Iq0deU

21. Clinical utility of comprehensive genomic profiling in pediatric acute leukemias

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Gordana Raca, Jianling Ji, Matthew Oberley, Deepa Bhojwani, Jaclyn Biegel, Matthew Hiemenz




https://ift.tt/2Gticvm

29. Development and validation of 15-min FISH hybridization technology for interphase and metaphase cytogenetic samples

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Ramesh Babu, Daniel L. Van Dyke, Stephen L. Papa, Ernesto Fuentes, Sarah Fuentes, Srikanthi Kopuri, Cynthia Williamson, Mingya Liu, Vaithilingam G. Dev, Jim Tepperberg, Stuart Schwartz, Peter Papenhausen, Prasad Koduru




https://ift.tt/2L6qn47

37. Microdeletions Including the RYR2 Gene Are Not Associated with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) in Four Unrelated Families

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Matthew Thomas, George McDaniel, Kaitlyn Amos, Eli Williams




https://ift.tt/2GqwD37

Editorial Board

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225





https://ift.tt/2IqTkdz

1. Detection of mosaicism and chimerism using SNP arrays in pediatric clinical testing: 10 year experience

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Laura K. Conlin, Brooke Weckselblatt, Jinbo Fan, Elaine Zackai, Matthew C. Dulik, Nancy B. Spinner, Minjie Luo




https://ift.tt/2GoLZ8g

23. Prevalence of KANK1-NTRK3 fusion in renal metanephric adenomas that lack BRAF mutations

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Aida Catic, Amina Kurtovic-Kozaric, Ardis Sophian, Lech Mazur, Faruk Skenderi, Ondrej Hes, Stephen Rohan, Dinesh Rakheja, Jillene Kogan, Michael R Pins




https://ift.tt/2L6yn5h

27. Treating patients with lymphoma as a paradigm for “personalized medicine”

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): James Armitage




https://ift.tt/2IoZUkH

31. Assessing telomere length and chromosome aberrations in twin and unrelated astronauts

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Susan M. Bailey, Miles J. McKenna, Lynn Taylor, Kerry A. George




https://ift.tt/2L5jO1G

4. Non-invasive prenatal screening: Understanding the underlying mechanisms for discordance

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Rupa Udani, Kim Oxendine, Jennifer Laffin, Vanessa Horner




https://ift.tt/2IneRDJ

35. Runs of homozygosity (ROH) reveal that segmental-UPD is associated with the repair of genomic imbalance

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Andrea Penton, Peter Papenhausen, Stuart Schwartz, James Tepperberg




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5. Modeling Synovial Sarcoma from initiation through metastasis

Publication date: August 2018
Source:Cancer Genetics, Volumes 224–225
Author(s): Mario Capecchi




https://ift.tt/2GoImPT

Un dernier Qui suis-je !

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): O. Laccourreye, A. Werner, I. McGill




https://ift.tt/2k12C0X

Reconstruction hypopharyngée à l’aide d’une pince à agrafage circulaire

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): P. Schultz, A. Dupret-Bories, S. Ciftci, L. Fath
L'anastomose distale par lambeau tubulisé est une des principales difficultés dans la reconstruction de l'hypopharynx. Si la probabilité de survie du lambeau est élevée grâce à l'expérience des équipes chirurgicales, deux complications restent courantes, la fistule et la sténose de la jonction lambeau- œsophage. L'usage d'une pince à agrafage circulaire permet de diminuer la fréquence de ces complications en réalisant une suture parfaitement circulaire et solide. La mise en place d'un stent salivaire n'est pas utile et l'alimentation peut-être reprise plus précocement. Son utilisation est simple moyennant quelques impératifs techniques, puisque les pinces disponibles n'ont pas été conçues dans cette indication. Nous décrivons ici, les indications, la procédure chirurgicale et les résultats globaux des cas réalisés. Le lambeau antébrachial est pour nous le lambeau idéal pour cette reconstruction, mais la technique autorise des lambeaux plus épais jusqu'au lambeau de grand pectoral avec cependant des résultats moins satisfaisants en terme de cicatrisation et de déglutition.



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Évaluation de l’efficacité de la labioglossopexie dans la triade de Pierre Robin

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): H. Broucqsault, M.-D. Lamblin, G. Hosana, P. Fayoux
ObjectifsÉvaluer l'efficacité de la labioglossopexie sur le SAOS par polysomnographie chez des enfants porteurs d'une séquence de Pierre Robin.Matériel et méthodesÉtude rétrospective monocentrique de 2004 à 2015 chez des enfants ayant bénéficié d'une labioglossopexie pour un syndrome d'apnée obstructif du sommeil dans le cadre d'un syndrome de Pierre Robin. Dans le cadre du bilan préopératoire, une polysomnographie et une endoscopie laryngotrachéale étaient réalisées. Les données recueillies étaient le diagnostic syndromique, l'assistance respiratoire en pré opératoire et ses modalités. Le syndrome d'apnée obstructif du sommeil était classé en 3 catégories selon sa sévérité. La polysomnographie de contrôle était réalisée 1 mois après l'intervention.RésultatsAu total, 37 patients ayant eu une labioglossopexie ont été inclus. L'âge médian lors de l'intervention était de 45jours (8–210). Au total, 31 patients avaient une séquence de Pierre Robin isolée et 6 avaient un syndrome associé. Tous les patients avaient un syndrome d'apnée obstructif du sommeil sévère nécessitant une aide respiratoire en préopératoire : 8 intubations orotrachéale, 15 ventilations non invasive, 14 sondes nasopharyngées. La labioglossopexie améliore significativement la saturation en oxygène, la capnie et l'index d'apnée hypopnée (p<0,005). Dans certains cas, l'amélioration n'était pas suffisante et nécessitait la réalisation d'une trachéotomie (n=5) ou la mise en place d'une ventilation non invasive (n=3).ConclusionLa labioglossopexie améliore l'obstruction respiratoire chez les enfants avec un syndrome de Pierre Robin permettant d'éviter dans la plupart des cas (n=29) des thérapeutiques plus invasives.



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Place de l’allergie dans la caractérisation phénotypique et endotypique de la polypose nasosinusienne

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): G. Mortuaire, I. Gengler, M. Balden, M. Capron, G. Lefèvre
ObjectifsÉvaluer la place de l'allergie en tant que facteur influençant la présentation clinique (phénotype) et le profil inflammatoire (endotype) de la polypose nasosinusienne (PNS).Matériel et méthodesUne étude prospective monocentrique était menée sur 18 mois incluant 57 patients suivis pour PNS en situation d'échec du traitement médical. L'allergie était diagnostiquée sur la concordance des tests cutanés allergéniques et des manifestations cliniques. L'analyse du profil phénotypique s'appuyait sur le score de sévérité clinique, la taille des polypes et le score tomodensitométrique de Lund-Mackay. Le profil endotypique était établi par la mesure des concentrations dans le sang et les sécrétions nasales en IgE totales, IgA, interleukine-5, interleukine-9, ECP et EDN. Les taux de polynucléaires éosinophiles dans le sang, les sécrétions nasales et le polype étaient aussi comparés.RésultatsLes profils phénotypiques et endotypiques des patients allergiques (n=15) et non allergiques (n=42) étaient comparables. Seuls l'asthme et les IgE totales sanguines étaient associés à la présence d'une allergie.ConclusionCe travail suggère que l'allergie n'est pas directement impliquée dans l'expression clinique et les processus inflammatoires de la PNS. À l'heure de nouvelles approches thérapeutiques ciblant les voies de signalisation inflammatoire, l'identification de marqueurs sanguins et tissulaires pertinents constitue l'axe de recherche la plus susceptible de modifier la prise en charge de la PNS.



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Laryngectomie totale et pharyngolaryngectomie totale pour carcinome épidermoïde du larynx et de l’hypopharynx : fréquence, distribution et facteurs de risque de survenue de métastases ganglionnaires

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): D. Riviere, J. Mancini, L. Santini, A. Giovanni, P. Dessi, N. Fakhry
ObjectifsÉvaluer la fréquence et la distribution des métastases ganglionnaires chez des patients opérés de laryngectomie totale ou de pharyngolaryngectomie totale.Matériel et méthodesÉtude rétrospective monocentrique réalisée à partir de 136 patients ayant bénéficié d'une laryngectomie totale ou d'une pharyngolaryngectomie totale pour carcinome épidermoïde pharyngolaryngé associée à un traitement chirurgical des aires ganglionnaires.RésultatsAu total, 110 patients présentaient une tumeur du larynx et 26 patients une tumeur de l'hypopharynx. Soixante-trois patients étaient opérés en première intention et 73 patients étaient opérés en situation de récidive. Le taux de métastases ganglionnaires confirmées histologiquement était de 44,8 %, quelle que soit la localisation de la tumeur primitive. La localisation tumorale hypopharyngée était un facteur de risque de métastases ganglionnaires (73,1 %, p=0,002) tout comme la sous-localisation tumorale sus-glottique (64,3 %, p=0,039). Les groupes IIa et III étaient envahis dans 28,7 % et 25,7 % des cas respectivement. Parmi les patients ayant bénéficié d'un évidement des groupes VIb, le taux d'envahissement ganglionnaire dans ces territoires était de 23,8 %. Le taux de récidive ganglionnaire était de 10,3 % dans les groupes II à IV et de 13,2 % dans les groupes VIb.ConclusionsQuelle que soit la localisation tumorale, les groupes IIa et III sont les plus fréquemment envahis. L'importance du taux d'envahissement histologique dans les groupes VIb évidés, mais également de récidive, doit faire discuter un évidement ganglionnaire prophylactique bilatéral systématique de ces territoires dans certaines localisations tumorales.



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Editorial Board

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3





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Comparaison entre le Video Head Impulse Test (VHIT) et les épreuves caloriques dans la maladie de Menière définie unilatérale à un stade avancé

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): F. Rubin, F. Simon, B. Verillaud, P. Herman, R. Kania, C. Hautefort
ObjectifPeu de publications étudient le VHIT au cours de la maladie de Menière (MM), et ces études sont contradictoires (certaines observent un VHIT systématiquement normal au cours de la maladie, et d'autres non). Ces incohérences pourraient peut-être être liées au fait que les patients les moins sévères auraient des résultats différents des patients les plus sévères. Le but de cette étude était de comparer les résultats du VHIT aux épreuves caloriques chez des patients atteints de MM définie unilatérale à un stade avancé.Matériel et méthodeÉtude prospective de 37 patients inclus consécutivement, d'âge moyen 56 ans (±12). La surdité moyenne était de 59dB HL (±18) et 12 patients subissaient des crises de Tumarkin. L'anormalité des caloriques était définie par une hyporéflexie d'au moins 20 %. L'anormalité du VHIT était définie par la présence de saccades ou d'un gain <0,64 pour les canaux verticaux et 0,78 pour les horizontaux.RésultatsTous les patients avaient un VHIT normal et 3 patients avaient un calorique normal. L'hyporéflexie moyenne était de 45 % aux caloriques.ConclusionÀ ce jour, ce travail est le seul publié utilisant l'actuelle définition de MM (août 2015). Cette étude suggère qu'en dehors de toute crise, le VHIT est normal au cours de la MM définie unilatérale à un stade avancé, ceci contrastant avec des caloriques anormaux. Cette situation inhabituelle pourrait aider les cliniciens à distinguer les hydrops d'autres maladies de l'oreille interne et il serait très intéressant d'étayer cette hypothèse en étudiant davantage de patients souffrant d'hydrops.



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Paralysie laryngée unilatérale idiopathique de l’adulte

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): F. Rubin, A. Villeneuve, L. Alciato, L. Slaïm, P. Bonfils, O. Laccourreye
ButAnalyse des caractéristiques de la paralysie laryngée unilatérale idiopathique de l'adulte.Matériel et méthodesÉtude rétrospective (difficultés diagnostiques, données cliniques, récupération) d'une cohorte de 100 patients avec une paralysie laryngée unilatérale idiopathique (groupe A) et comparaison avec une cohorte de 211 patients avec une paralysie laryngée unilatérale isolée non idiopathique et non traumatique (groupe B).RésultatsUne difficulté diagnostique était notée dans 24 % des cas, au sein du groupe A : huit patients avec une affection virale ORL commune concomitante à l'apparition de la paralysie, cinq patients avec une affection concomitante pouvant entrainer une immunodépression et 11 patients chez qui la surveillance notait l'apparition d'une affection tumorale maligne sur le trajet des nerfs pneumogastrique et laryngé ipsilatéraux ou au sein du larynx paralysé. En analyse actuarielle, aucune récupération de la mobilité laryngée ne survenait après le 51^e mois suivant le début de la paralysie pour un taux actuariel de récupération à cinq ans de 53,2 % dans le groupe A et de 17,9 % dans le groupe B (p<0,0001). Au sein du groupe A, la récupération de la mobilité laryngée survenait avant la fin de la deuxième année dans 93 % des cas. En analyse monovariée, la récupération de la mobilité laryngée au sein du groupe A était d'autant plus fréquente que le sujet était jeune (p=0,033), que le délai de consultation était court (p<0,001), et qu'il n'existait pas d'antécédent carcinologique (p=0,028). En l'absence de récupération, au sein du groupe A, une pathologie tumorale maligne sur le trajet des nerfs pneumogastrique ou laryngé inférieur ipsilatéraux apparaissait dans 17,2 % des cas dont 81 % étaient dépistés dans les 30 mois qui suivaient le début de la paralysie.ConclusionEn présence d'une paralysie laryngée unilatérale non traumatique isolée et en l'absence de récupération de la mobilité laryngée, chez l'adulte, une surveillance régulière poursuivie au moins trois ans est conseillée.



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Modèles animaux de l’otite moyenne aiguë – une mise au point avec des implications pratiques pour la recherche en laboratoire

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): N.H. Davidoss, Y.K. Varsak, P.L. Santa Maria
Un nombre considérable d'études animales s'est concentré sur le développement de nouvelles stratégies pour la prévention et le traitement de l'otite moyenne aiguë (OMA). Plusieurs modèles expérimentaux de l'OMA ont ainsi été développés. L'analyse de la littérature publiée dans la base de données PubMed, sur la période allant de 1975 à juillet 2016, en utilisant les mots clés « animal model » et « otitis media », notait 91 études et 123 modèles animaux. Le rat, la souris et le chincilla étaient les animaux les plus fréquemment utilisés pour les modèles expérimentaux d'OMA, avec leurs avantages et leurs désavantages propres. Streptococcus pneumoniae, Haemophilus influenzae et Moraxella catarrhalis, Streptococcus pneumoniae (types 3, 23 et 6A) et Haemophilus influenzae non typable (HINT) étaient les pathogènes les plus couramment utilisés pour induire des OMA chez les rats et les souris. L'ajout de pathogènes viraux tels que le VRS et le virus Influenza A, couplé à l'induction de dysfonctionnements au niveau des trompes d'Eustache, peut aussi être utile dans les modèles animaux de l'OMA. La prophylaxie antibiotique peut également interférer avec la réponse immunitaire sans réduire de manière significative la mortalité animale.



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La polypose nasale (ou rhinite olfactive chronique)

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): R. Jankowski, C. Rumeau, P. Gallet, D.T. Nguyen
Le concept de rhinosinusite chronique avec ou sans polype repose sur l'unicité structurale et fonctionnelle de la muqueuse pituitaire et sa réponse univoque aux agressions de l'environnement (allergènes, virus, bactéries, pollution…). Il est confronté dans la présente mise au point à la théorie évo-dévo des trois nez qui, au contraire, individualise la polypose nasale comme une maladie intrinsèque du nez olfactif et en particulier de la muqueuse non olfactive de l'ethmoïde (qui dans la théorie évo-dévo n'est pas un sinus mais l'os de la base du crâne abritant la muqueuse olfactive). L'approche évo-dévo permet un diagnostic positif simple et précis de la polypose nasale et de ses différentes formes cliniques, améliore le diagnostic différentiel en précisant les maladies chroniques du nez respiratoire et celles des sinus paranasaux, soulève l'hypothèse d'une origine auto-immune dirigée spécifiquement contre des auto-antigènes du système olfactif, et corrobore le concept chirurgical de nasalisation aux détriments de celui de chirurgie fonctionnelle des sinus et du complexe ostio-méatal. La ventilation sinusienne semble en effet mineure par rapport à sa fonction de production, stockage et libération active de monoxyde d'azote (NO) utile à l'oxygénation du sang artériel au niveau des alvéoles pulmonaires. Cette fonction respiratoire des sinus paranasaux est peut-être la plus importante de celles qui leur ont été attribuées. Le piégeage du NO dans les espaces ethmoïdaux permet en outre de comprendre certains aspects radiologiques associés à la polypose nasale.



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Technique de l’épiglottoplastie dans la chirurgie partielle du larynx par voie endoscopique

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): M. Moulin, C.A. Righini, P.F. Castellanos, I. Atallah
L'intérêt de la chirurgie partielle du larynx par voie endoscopique est de réaliser une exérèse tumorale de qualité tout en limitant les séquelles fonctionnelles permettant ainsi l'amélioration des suites postopératoires. Dans ce type de chirurgie, l'épiglotte est souvent partiellement sectionnée avec une zone d'exérèse laissée en cicatrisation dirigée, sans temps de reconstruction. La technique chirurgicale présentée s'intéresse au temps de reconstruction endoscopique en cas de section partielle de l'épiglotte. La suture du bord sectionné de l'épiglotte à la base de langue permet de recréer une néo-épiglotte avec un plan valléculaire, se rapprochant ainsi de l'anatomie préopératoire afin d'améliorer les capacités de déglutition dans les suites opératoires.



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L’injection de toxine botulinique par voie endoscopique en ambulatoire dans les mouvements anormaux du larynx

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): A. Kaderbay, C.A. Righini, P.F. Castellanos, I. Atallah
IntroductionL'injection de toxine botulinique est largement utilisée dans le traitement des mouvements anormaux du larynx. L'injection transcutanée sous contrôle électromyographique est la technique la plus commune pour réaliser l'injection intra-laryngée de toxine botulinique.ObjectifNous décrivons une approche endoscopique pour l'injection intra-laryngée de toxine botulinique sous anesthésie locale sans avoir recours à l'électromyographie.TechniqueUn vidéo-endoscope flexible avec un canal opérateur est utilisé. Après une anesthésie locale du larynx par instillation de lidocaïne, une aiguille flexible est insérée dans le canal opérateur afin d'injecter la dose désirée de toxine botulinique dans les plis vocaux et/ou vestibulaires.ConclusionL'injection de toxine botulinique par voie endoscopique sous anesthésie locale dans les mouvements anormaux du larynx est une technique fiable. Elle peut être réalisée par tout laryngologiste sans avoir recours à l'électromyographie. Elle est pratique pour l'opérateur et confortable pour le patient.



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Syndrome de Forestier et apnée obstructive du sommeil : traitement chirurgical

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): D.K. Ribeiro, J.A. Pinto, G.S. Freitas
IntroductionNous rapportons un cas d'apnée obstructive du sommeil causé par la maladie de Forestier et décrivons le traitement chirurgical réalisé.RésuméUn patient de 56 ans présentait une dysphagie aux solides et liquides, ainsi qu'un ronflement (score coté à 10) et une somnolence diurne excessive depuis cinq ans. Lors de l'examen nasofibroscopique, il y avait un œdème de la région inter-aryténoïdienne et une protrusion de la paroi postérieure du larynx. La radiographie cervicale a montré une protrusion des disques intervertébraux entre C3-C5 (hyperostose squelettique) et la polysomnographie a révélé un index d'apnée-hypopnée (IAH) de 56 événements/h. La chirurgie a été réalisée par les équipes d'otorhinolaryngologie et d'orthopédie. Le patient a évolué vers une résolution complète des symptômes et un IAH de 3,9 événements/h à la polysomnographie de contrôle.DiscussionIl s'agit du premier cas de syndrome de Forestier (SF) associé à l'apnée obstructive du sommeil (AOS) traitée par chirurgie avec amélioration complète des symptômes.



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Schwannome du sinus frontal

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): J. Petersen, L. Gilain, A. Coutu, N. Saroul
IntroductionLes schwannomes nasosinusiens sont rares, et particulièrement au niveau du sinus frontal.Cas cliniqueNous rapportons le cas d'une patiente atteinte d'un schwannome du sinus frontal gauche découvert lors d'une complication à type de sinusite frontale avec complications orbitaire et oculaire. Le geste a consisté en une exérèse tumorale par voie endonasale et un drainage par voie externe.DiscussionL'origine des schwannomes du sinus frontal sont multiples avec des expressions clinico-radiologiques variées, rendant leur diagnostic difficile leur exérèse étant par ailleurs complexe.



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Anosmie et obstruction nasale

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): J.J. Braun, S. Riehm




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Papillomatose laryngée au Sénégal : bilan d’une experience de 10 ans

Publication date: June 2018
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 135, Issue 3
Author(s): S. Maiga, C. Ndiaye, M. Diouf, B.K. Diallo, M. Ndiaye, M.S. Diouf, I.C. Ndiaye, R. Diouf
ObjectifsLes objectifs de cette étude étaient de montrer les aspects épidémiologiques, cliniques et thérapeutiques de la papillomatose laryngée, dans les services d'ORL et de chirurgie cervicofaciale du centre hospitalier national universitaire de Fann, Dakar, Sénégal.Patients et méthodesIl s'agit d'une étude rétrospective menée à la clinique ORL Lamine Sine Diop du CHNU de Fann du 01 janvier 2006 au 31 décembre 2015 concernant tous les patients hospitalisés pour la prise en charge d'une papillomatose laryngée. Les paramètres étudiés étaient épidémiologiques, cliniques et thérapeutiques. Les données obtenues ont été analysées par le logiciel spécialisé dans le traitement des données statistiques « SPSS 18 ».RésultatsL'âge médian au moment du diagnostic était de 11 ans, le sex-ratio était de 1,88. Le délai moyen de consultation était de 4,5 ans. La dysphonie était le symptôme le plus constant, elle était présente dans tous les cas, suivie de la dyspnée laryngée qui était présente dans 64,6 % des cas. La localisation glottique était présente chez tous les patients soit 100 % des cas. Une trachéotomie était réalisée chez 20,8 % des cas. Tous les patients de notre étude ont bénéficié d'une exérèse per endoscopique des papillomes à la pince.ConclusionLa papillomatose laryngée est la plus fréquente des tumeurs bénignes de l'enfant, mais elle peut aussi débuter à l'âge adulte. Son traitement a été révolutionné par les progrès de l'endoscopie et des traitements antiviraux. Cependant, la trachéotomie occupe toujours une place importante dans notre pratique.



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Biomimetic soft fibrous hydrogels for contractile and pharmacologically responsive smooth muscle

Publication date: Available online 10 May 2018
Source:Acta Biomaterialia
Author(s): Yonghui Ding, Xin Xu, Sadhana Sharma, Michael Floren, Kurt Stenmark, Stephanie J. Bryant, Corey P. Neu, Wei Tan
The ability to assess changes in smooth muscle contractility and pharmacological responsiveness in normal or pathological-relevant vascular tissue environments is critical to enable vascular drug discovery. However, major challenges remain in both capturing the complexity of in vivo vascular remodeling and evaluating cell contractility in complex, tissue-like environments. Herein, we developed a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition to resemble the native vascular tissue environment. This hydrogel platform was further combined with the combinatory protein array technology as well as advanced approaches to measure cell mechanics and contractility, thus permitting evaluation of smooth muscle functions in a variety of tissue-like microenvironments. Our results demonstrated that biomimetic fibrous structure played a dominant role in smooth muscle function, while the presentation of adhesion proteins co-regulated it to various degrees. Specifically, fibre networks enabled cell infiltration and upregulated expression of actomyosin proteins in contrast to flat hydrogels. Remarkably, fibrous structure and physiologically relevant stiffness of hydrogels cooperatively enhanced smooth muscle contractility and pharmacological responses to vasoactive drugs at both the single cell and intact tissue levels. Together, this study is the first to demonstrate alterations of human vascular smooth muscle contractility and pharmacological responsiveness in biomimetic soft, fibrous environments with a cellular array platform. The integrated platform produced here could enable investigations for pathobiology and pharmacological interventions by developing a broad range of patho-physiologically relevant in vitro tissue models.Statement of SignificanceEngineering functional smooth muscle in vitro holds the great potential for diseased tissue replacement and drug testing. A central challenge is recapitulating the smooth muscle contractility and pharmacological responses given its significant phenotypic plasticity in response to changes in environment. We present a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition that enables the creation of functional smooth muscle tissues in the native vascular tissue-like microenvironment. Such fibrous hydrogel is further combined with the combinatory protein array technology to construct cellular array for evaluation of smooth muscle phenotype, contraction, and cell mechanics. The integrated platform produced here could be promising for developing a broad range of normal or diseased in vitro tissue models.

Graphical abstract

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Alternate vaccine strain selection in the wake of emerging foot-and-mouth disease virus serotype A antigenic variants in India

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Jajati Keshari Mohapatra, Biswajit Das, Manoranjan Rout, B.P. Sreenivasa, Saravanan Subramaniam, Aniket Sanyal, Bramhadev Pattnaik
'National foot-and-mouth disease (FMD) control programme' is being implemented in India and therefore predicting vaccine match is a key surveillance task. Recently, a considerable proportion of field viruses (75.6%) showed antigenic drift from the existing serotype A vaccine strain A IND 40/2000 necessitating search for an alternate strain. Here, antigenic relationship ('r1' value) of 87 field viruses with each of the 8 candidate strains was estimated by virus neutralization test. A IND 27/2011 strain emerged to be the one with the widest spectrum of antigenic coverage showing 'r1' value of more than 0.3 with 81.6% of field strains. It achieved a reasonably high titre of log10 7.5 TCID50/ml in BHK-21 suspension cell which was accompanied by positive charge gaining substitutions (E82–K and E131–K in VP2) thought to have adaptive significance. However, potency trial remains to be conducted before A IND 27/2011 finds a place in the vaccine formulation.



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An audit of the reliability of influenza vaccination and medical information extracted from eHealth records in general practice

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Annette K. Regan, Robyn A. Gibbs, Paul V. Effler
To evaluate the reliability of information in general practice (GP) electronic health records (EHRs), 2100 adult patients were randomly selected for interview regarding the presence of specific medical conditions and recent influenza vaccination. Agreement between self-report and data extracted from EHRs was compared using Cohen's kappa coefficient (k) and interpreted in accordance with Altman's Kappa Benchmarking criteria; 377 (18%) patients declined participation, and 608 (29%) could not be contacted. Of 1115 (53%) remaining, 856 (77%) were active patients (≥3 visits to the GP practice in the last two years) who provided complete information for analysis. Although a higher proportion of patients self-reported being vaccinated or having a medical condition compared to the EHR (50.7% vs 36.9%, and 39.4% vs 30.3%, respectively), there was "good" agreement between self-report and EHR for both vaccination status (κ = 0.67) and medical conditions (κ = 0.66). These findings suggest EHR may be useful for public health surveillance.



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Recent advances in the development of vaccines for chronic inflammatory autoimmune diseases

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Naru Zhang, Kutty Selva Nandakumar
Chronic inflammatory autoimmune diseases leading to target tissue destruction and disability are not only causing increase in patients' suffering but also contribute to huge economic burden for the society. General increase in life expectancy and high prevalence of these diseases both in elderly and younger population emphasize the importance of developing safe and effective vaccines. In this review, at first the possible mechanisms and risk factors associated with chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D) are discussed. Current advances in the development of vaccines for such autoimmune diseases, particularly those based on DNA, altered peptide ligands and peptide loaded MHC II complexes are discussed in detail. Finally, strategies for improving the efficacy of potential vaccines are explored.



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Final analysis of a study assessing genital human papillomavirus genoprevalence in young Australian women, following eight years of a national vaccination program

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Suzanne M. Garland, Alyssa M. Cornall, Julia M.L. Brotherton, John D. Wark, Michael J. Malloy, Sepehr N. Tabrizi
ObjectivesThe VACCINE [Vaccine Against Cervical Cancer Impact and Effectiveness] study evaluated the prevalence of quadrivalent vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst young women of vaccine-eligible age.MethodsBetween October 2011 – June 2015, women aged 18–25 years from Victoria, Australia, were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire and provided a self-collected vaginal swab for HPV DNA detection and genotyping (Linear Array HPV genotyping assay). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR).ResultsOf 1223 who agreed to participate, 916 (74.9%) completed the survey and, for 1007 (82.3%) sexually-active participants, 744 (73.9%) returned the self-collected swab, of which 737 contained detectable DNA. 184/737 (25.0%) were positive for HPV. Vaccine-targeted HPV genotypes were detected in only 13 (1.7%) women: 11 HPV 16 (six vaccinated after sexual debut, five unvaccinated) and two HPV 6. Prevalence of any of HPV 31/33/45 collectively was 2.9%, varying significantly by vaccination status (fully 2.0%, unvaccinated 6.8%; p = 0.01). Vaccination rates among the sexually-active cohort were high, with 65.6%, 71.6% and 74.2% of participants having received three, at least two or at least one dose of vaccine, respectively. Of women self-reporting HPV vaccination, the NHVPR confirmed one or more doses were received in 90%. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners.ConclusionSurveillance five to eight years' post-initiation of a national HPV vaccination program demonstrated a consistent and very low prevalence of vaccine-related HPV genotypes and some evidence of cross protection against related types amongst vaccine-eligible women from Victoria, Australia.



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Editorial Board/Aims and Scope

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23





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Population-level factors predicting variation in influenza vaccine uptake among adults and young children in England, 2015/16 and 2016/17

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): E. Tessier, F. Warburton, C. Tsang, S. Rafeeq, N. Boddington, M. Sinnathamby, R. Pebody
England's influenza vaccination programme targets persons with clinical risk factors, pregnant women, those aged 65 years and older and children. Low vaccine uptake amongst primary school children was previously found to be significantly associated with increasing deprivation, Black or Minority Ethnic (BME) and certain religions. It is unknown whether these population predictors are associated with vaccine uptake in other groups. GP level data for target groups during the 2015/16 and 2016/17 seasons were linearly regressed against various factors to determine potential predictors associated with variation in uptake.Adjusted uptake for 2–4 year olds during both seasons was more than 11% lower in the most deprived decile and more than 3% lower in 34%+ BME populations compared to the least deprived and non-BME populations. Pregnant women in deprived areas had significantly lower vaccine uptake than in non-deprived areas. Patients 16–64 years old at risk showed no significant variation in uptake by deprivation, whereas patients 65 years and older had more than 3% higher vaccine uptake in the least deprived populations than the most deprived populations. Areas with the highest Muslim and BME populations had a significantly higher vaccine uptake among patients ages 16 to under 65 years old in a clinical risk group than non-Muslim and non-BME populations during both seasons. Population-factors have different effects on vaccine uptake for the various target groups. These findings support segmenting public health activities to improve vaccine uptake and reduce inequalities.



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Estimating effectiveness of HPV vaccination against HPV infection from post-vaccination data in the absence of baseline data

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Simopekka Vänskä, Anna Söderlund-Strand, Ingrid Uhnoo, Matti Lehtinen, Joakim Dillner
BackgroundHPV vaccination programs have been introduced in large parts of the world, but monitoring of effectiveness is not routinely performed. Many countries introduced vaccination programs without establishing the baseline of HPV prevalences. We developed and validated methods to estimate protective effectiveness (PE) of vaccination from the post-vaccination data alone using references, which are invariant under HPV vaccination.MethodsType-specific HPV prevalence data for 15–39 year-old women were collected from the pre- and post-vaccination era in a region in southern Sweden. In a region in middle Sweden, where no baseline data had been collected, only post-vaccination data was collected. The age-specific baseline prevalence of vaccine HPV types (vtHPV, HPV 6, 11, 16, 18) were reconstructed as Beta distributions from post-vaccination data by applying the reference odds ratios between the target HPV type and non-vaccine-type HPV (nvtHPV) prevalences. Older non-vaccinated age cohorts and the southern Sweden region were used as the references. The methods for baseline reconstructions were validated by computing the Bhattacharyya coefficient (BC), a measure for divergence, between reconstructed and actual observed prevalences for vaccine HPV types in Southern Sweden, and in addition, for non-vaccine types in both regions. The PE estimates among 18–21 year-old women were validated by comparing the PE estimates that were based on the reconstructed baseline prevalences against the PE estimates based on the actual baseline prevalences.ResultsIn Southern Sweden the PEs against vtHPV were 52.2% (95% CI: 44.9–58.5) using the reconstructed baseline and 49.6% (43.2–55.5) using the actual baseline, with high BC 82.7% between the reconstructed and actual baseline. In the middle Sweden region where baseline data was missing, the PE was estimated at 40.5% (31.6–48.5).ConclusionsProtective effectiveness of HPV vaccination can be estimated from post-vaccination data alone via reconstructing the baseline using non-vaccine HPV type data.



https://ift.tt/2Gq8SIz

Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Garth S. Herbert, Timothy J. Vreeland, Guy T. Clifton, Julia M. Greene, Doreen O. Jackson, Mark O. Hardin, Diane F. Hale, John S. Berry, Pauline Nichol, Sook Yin, Xianzhong Yu, Thomas E Wagner, George E. Peoples
IntroductionTumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial results.MethodsThis trial includes patients with any stage solid tumors, ECOG ≤1, and >4 months life-expectancy. A personalized vaccine is created using 1 mg of tumor and 120 ml blood (to isolate DC). Primary vaccination series (PVS) is four monthly inoculations. Patients are followed per standard of care (SOC). Endpoints include safety and tumor response (RECIST v1.1).Results44 patients were enrolled and vaccinated consisting of 31 late stage patients with residual/measurable disease, and 13 disease-free patients after SOC therapies. While 4 patients progressed before completing the PVS, 12/31 (39%) demonstrated clinical benefit (2 complete responses, 4 partial responses, 6 stable disease). In the adjuvant setting, 46% of late stage patients remain disease free at a median of 22.5 months.ConclusionsThe TLPLDC vaccine is scalable, generates a personalized DC vaccine, and requires little autologous tumor tissue and few DC. The vaccine is safe, with primarily grade 0–2 toxicities, and nearly 40% clinical benefit rate in varied tumors, warranting further study.Trial Registration: ISRCTN81339386, Registered 2/17/2016.



https://ift.tt/2L87Nsw

The effect of exercise on vaccine-related pain, anxiety and fear during HPV vaccinations in adolescents

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): V.Y. Lee, R. Booy, R. Skinner, K.M. Edwards
IntroductionWith increased school-based vaccinations for improved coverage rates and practicality, the World Health Organization (WHO) recently endorsed research to identify possible interventions to reduce vaccine-related pain in mass clinical and school-based settings. In particular, the lack of research in adolescents indicate a particular need in this population. Acute exercise has analgesic effects and has been used as a behavioural adjuvant to vaccination. Here, we examine the effect of exercise on vaccine-related pain, anxiety and fear in adolescents, during a school-based program for HPV vaccinations.Methods116 students (Female: 61, Male: 55) aged 11–13 years were randomly allocated to either an Exercise (n = 60) or Control (n = 56) group. All participants completed demographic and Trait-anxiety questionnaires prior to receiving the vaccine according to usual care. The Exercise group also performed upper body exercise for 15 min prior to receiving the vaccine. Immediately after the vaccine administration, all participants reported on pain, anxiety and fear at the time of receiving the vaccine.ResultsFemale adolescents in the Exercise group reported significantly less pain (3.64; 95% CI, 2.98–4.30) than Controls (4.58; 95% CI, 3.96–5.19; p = 0.04). Further, females reported greater pain and anxiety than males in the Control group but not the Exercise group.ConclusionThis study supports the use of exercise prior to vaccine administration, especially in female adolescents who are particularly vulnerable to negative experiences during vaccination procedures. Furthermore, the ease of application, as well as the benefit of exercise, provides support for the use of simple exercise prior to vaccination in mass vaccination settings.Clinical trial registry: ANZCTR, ACTRN12614001185651.



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Enhancing immunization during second year of life by reducing missed opportunities for vaccinations in 46 countries

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Celina M. Hanson, Imran Mirza, Richard Kumapley, Ikechukwu Ogbuanu, Robert Kezaala, Robin Nandy
BackgroundDelivering vaccination services during the second year of life (2YL)1 Abbreviations: 2YL, denotes Second Year of Life or 2nd Year of Life.¹ provides countries with an opportunity to achieve greater coverage, to provide booster doses and vaccines missed during the first year of life, as well as contribute towards disease control and elimination goals.MethodsUsing data from demographic health surveys (DHSs) conducted during 2010 to 2016, this paper explores the proportion of missed opportunities for vaccinations generally provided during routine immunization among children in their 2YL.ResultsDHS data in 46 countries surveyed 478,737 children, from which 169,259 children were 12–23 months old and had vaccination/health cards viewed by surveyors. From this group, 69,489 children aged 12–23 months had contact with health services in their 2YL. Three scenarios for a missed opportunity for vaccinations were analysed: (1) a child received one vaccine in the immunization schedule and was eligible for another vaccine, but did not receive any further vaccination, (2) a child received a vitamin A supplementation (VAS) and was due for a vaccine, but did not receive vaccines that were due, and (3) a child was taken to a health facility for a sick visit and was due (and eligible) for a vaccine, but did not receive the vaccine. A total of 16,409 (24%) children had one or more missed opportunities for vaccinations.ConclusionThis analysis highlights the magnitude of the problem of missed opportunities in the 2YL. The global community needs to provide better streamlined guidance, policies and strategies to promote vaccination screenings at well-child and sick child visits in the 2YL. Where they do not exist, well-child visits in the 2YL should be established and strengthened.



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Porcine reproductive and respiratory syndrome virus expressing E2 of classical swine fever virus protects pigs from a lethal challenge of highly-pathogenic PRRSV and CSFV

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Fei Gao, Yifeng Jiang, Guoxin Li, Yanjun Zhou, Lingxue Yu, Liwei Li, Wu Tong, Hao Zheng, Yujiao Zhang, Hai Yu, Tongling Shan, Shen Yang, Huan Liu, Kuan Zhao, Guangzhi Tong
Porcine reproductive and respiratory syndrome (PRRS) and classical swine fever (CSF) are economically significant diseases that affect the swine industry worldwide. However, the current vaccination strategy, which uses two single live attenuated vaccines, can result in interference for each other. In addition, the universally used CSFV vaccine C-strain does not allow for differentiation of infected and vaccinated animals. In this study, rPRRSV-E2, PRRS virus (PRRSV) expressing CSF virus (CSFV) E2, was constructed by reverse genetics. The E2 gene of CSFV was inserted between ORF1b and ORF2 in the genome of the PRRS vaccine virus, HuN4-F112. A copy of transcriptional regulatory sequence 6 was inserted at the 3′ terminal of the exogenous gene to produce CSFV E2 as a unique subgenomic mRNA transcript. The rPRRSV-E2 was stable for at least 25 serial cell passages. Single-shot intramuscular immunization of rPRRSV-E2 into pigs induced PRRSV-specific and CSFV-specific antibodies and fully protected pigs from lethal challenge with highly-pathogenic PRRSV and CSFV. These results demonstrate that a novel strategy for recombinant PRRSV production is effective, and suggest that rPRRSV-E2 is a promising live, virus-vectored vaccine against PRRS and a marker vaccine against CSF.



https://ift.tt/2Gp702O

Evaluation of the association of pneumococcal conjugate vaccine immunization and density of nasopharyngeal bacterial colonization using a multiplex quantitative polymerase chain reaction assay

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Courtney P. Olwagen, Peter V. Adrian, Marta C. Nunes, Shabir A. Madhi
BackgroundNasopharyngeal bacterial colonization is a pre-requisite for developing bacterial mucosal and invasive disease. Pneumococcal conjugate vaccine (PCV) immunization of children reduces their risk of colonization by vaccine-serotypes, which could affect the biome of the nasopharynx in relation to colonization by other bacteria. This study evaluated the association of PCV immunization on the prevalence density of nasopharyngeal colonization by common, potentially pathogenic bacteria.MethodsA multiplex qPCR assay was used to evaluate bacterial nasopharyngeal colonization by 7-valent PCV (PCV7) serotypes, non-vaccine serotypes (NVT), Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Neisseria meningitidis in PCV7-vaccinated and PCV-unvaccinated African children at two time points.ResultsPCV7 vaccination was associated with a higher prevalence of NVT and H. influenzae at 9 and 16 months, respectively. While the prevalence of S. aureus was higher in PCV7-vaccinated children at 9 months, no difference was found at 16 months. The density of PCV7 serotypes (3.8 vs. 3.4 log10; p = 0.048), NVT (3.6 vs. 3.1 log10; p = 0.018), H. influenzae (4.34 vs. 3.86 log10; p = 0.008), M. catarrhalis (3.52 vs. 2.98 log10; p < 0.001) and S. aureus (4.02 vs. 3.06 log10; p = 0.02) was higher among PCV-vaccinated compared to PCV-unvaccinated children at 9 months, although, this difference diminished at 16 months of age.ConclusionThe reduction in PCV7-serotype colonization impacted on colonization prevalence and density of other bacterial species of the nasopharynx. The clinical relevance of this needs further exploration in relation to mucosal and invasive disease outcomes, as well as for higher valency PCV vaccines.



https://ift.tt/2IpT9io

Viable spores of Coccidioides posadasii Δcps1 are required for vaccination and provide long lasting immunity

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Lisa F. Shubitz, Daniel A. Powell, Hien T. Trinh, M. Lourdes Lewis, Marc J. Orbach, Jeffrey A. Frelinger, John N. Galgiani
Coccidioidomycosis is a systemic fungal infection for which a vaccine has been sought for over fifty years. The avirulent Coccidioides posadasii strain, Δcps1, which is missing a 6 kb gene, showed significant protection in mice. These studies explore conditions of protection in mice and elucidate the immune response. Mice were vaccinated with different doses and viability states of Δcps1 spores, challenged with virulent C. posadasii, and sacrificed at various endpoints, dependent on experimental objectives. Tissues from vaccinated mice were harvested for in vitro elucidation of immune response. Vaccination with viable Δcps1 spores was required for protection from lethal challenge. Viable spore vaccination produced durable immunity, lasting at least 6 months, and prolonged survival (≥6 months). The C. posadasii vaccine strain also protected mice against C. immitis (survival ≥ 6 months). Cytokines from infected lungs of vaccinated mice in the first four days after Cp challenge showed significant increases of IFN-γ, as did stimulated CD4⁺ spleen cells from vaccinated mice. Transfer of CD4⁺ cells, but not CD8⁺ or B cells, reduced fungal burdens following challenge. IFN-γ from CD4⁺ cells in vaccinated mice indicates a Th1 response, which is critical for host control of coccidioidomycosis.



https://ift.tt/2GoVqEL

Antibody persistence and booster response 68 months after vaccination at 2–10 years of age with one dose of MenACWY-TT conjugate vaccine

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Markus Knuf, Klaus Helm, Devayani Kolhe, Marie Van Der Wielen, Yaela Baine
BackgroundWe evaluated antibody persistence up to 68 months (M) post-vaccination with a quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) or a licensed monovalent MenC conjugate vaccine (MenC-CRM197) and subsequent booster responses to MenACWY-TT in healthy European children.MethodsIn the initial study (NCT00674583), healthy children, 2–10 years of age, were randomized to receive a single dose of either MenACWY-TT or MenC-CRM197. In the follow-up study, we present the persistence at 32, 44, 56, and 68 M post-vaccination, overall and stratified by age (2–5 and 6–10 years), and the immunogenicity and safety of MenACWY-TT administered to all study participants at M68 post-primary vaccination.ResultsAt M68, 33.3% (age group 2–5 years) and 47.1% (age group 6–10 years) of the children vaccinated with MenACWY-TT, and 50.0% (age group 2–5 years) and 75.9% (age group 6–10 years) vaccinated with MenC-CRM197 retained titers ≥1:8 for MenC, as assessed by a serum bactericidal assay using rabbit complement (rSBA). In the MenACWY-TT recipients, the percentages of children retaining rSBA titers ≥1:8 for MenA, MenW, and MenY were 81.7%, 47.3% and 66.7% in age group 2–5 years and 91.8%, 58,8% and 76.5% in age group 6–10 years, respectively. The booster dose induced robust responses (100% for all serogroups) and was well-tolerated.ConclusionsAntibody persistence (rSBA titers ≥ 1:8) for serogroups A, W and Y was observed in more than 50.0% of the children 68 M after receiving one dose of MenACWY-TT; for MenC, antibody persistence was observed in more than one third of MenACWY-TT and more than half of MenC-CRM197 recipients. Vaccination with a booster dose of MenACWY-TT induced robust immune responses for all serogroups.



https://ift.tt/2L9SwqO

Long-term impact of childhood hepatitis B vaccination programs on prevalence among Aboriginal and non-Aboriginal women giving birth in Western Australia

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): J. Reekie, J.M. Kaldor, D.B. Mak, J. Ward, B. Donovan, J.S. Hocking, D. Preen, B. Liu
Background/AimsTo evaluate the long-term effect of infant and childhood hepatitis B (HBV) vaccination programs among birthing women in Western Australia.MethodsA cohort of Western Australian women born from 1974 to 1995 was created using Birth Registrations and Electoral Roll records. They were linked to a perinatal register and notifiable diseases register to identify women having respectively their first births between 2000 and 2012 and diagnoses of HBV infections. HBV prevalence was estimated in Aboriginal and non-Aboriginal women, and according to maternal birth year cohorts.ResultsOf 66,073 women, 155 (0.23%) had a linked non-acute HBV notification. HBV prevalence was five times higher in Aboriginal women compared to their non-Aboriginal counterparts (0.92%, 95%CI 0.65–1.18 versus 0.18%, 0.15–0.21). Among Aboriginal women, after adjusting for year of giving birth and region of residence, those born in the targeted infant and school-based vaccination era (maternal year of birth 1988–1995) had an 89% lower risk (adjusted odds ratio [aOR] 0.11, 0.04–0.33) of HBV than those born in the pre-vaccination era (1974–1981). Prevalence also differed between Aboriginal women residing in rural/remote areas compared to those in major cities (aOR 3.06, 1.36–6.88). Among non-Aboriginal women, no significant difference in HBV prevalence was observed by maternal birth cohort (p = 0.20) nor by residence (p = 0.23), but there were significant differences by ethnicity with a 36-fold higher prevalence (aOR 36.08, 22.66–57.46) in non-Caucasian versus Caucasian women.ConclusionsA significant decline in HBV prevalence in Aboriginal birthing mothers was observed following the introduction of HBV vaccination programs in Western Australia. There were also considerable disparities in prevalence between women by area of residence and ethnicity. Our findings reflect those observed in women in other Australian jurisdictions. Continued surveillance of HBV prevalence in birthing mothers will provide ongoing estimates of HBV vaccination program impact across Australia and the populations most at risk of chronic HBV.



https://ift.tt/2ImG8X4

Long-term immunogenicity of a quadrivalent human papillomavirus vaccine in systemic lupus erythematosus

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): C.C. Mok, L.Y. Ho, C.H. To
ObjectivesTo evaluate the 5-year immunogenicity of a quadrivalent human papillomavirus (HPV) vaccine (GARDASIL) in patients with systemic lupus erythematosus (SLE).MethodsFemale SLE patients and controls, aged 18–35 years, who received GARDASIL in 2011 and sero-converted 12 months post-vaccination were followed for persistence of immunogenicity. Antibody measurement to HPV serotypes 6, 11, 16, 18 was repeated at 5 years. The rate of sero-reversion was compared between patients and controls, and factors associated with sero-reversion of the anti-HPV antibodies were studied.Results50 SLE patients and 50 controls were vaccinated with GARDASIL. Among subjects who sero-converted at 1 year and consented for this study, antibodies to HPV serotypes 6, 11, 16 and 18 at 5 years were persistent in 24/27 (89%), 26/31 (84%), 32/34 (94%) and 24/25 (96%) of the SLE patients; and 32/33 (97%), 32/33 (97%), 32/32 (100%) and 23/24 (96%) of the controls, respectively. Antibody titers to HPV-6 and 16 were significantly lower in patients than controls. Seven (21%) SLE patients had sero-reversion of ≥1 anti-HPV antibodies. Sero-reverted patients experienced significantly more SLE flares, particularly renal, and had received significantly higher cumulative doses of prednisolone, mycophenolate mofetil and tacrolimus than those with persistent immunogenicity. The cumulative doses of prednisolone correlated inversely and significantly with the anti-HPV 6, 11, and 16 titers at 5 years.ConclusionsImmunogenicity of the quadrivalent HPV vaccine was retained in a high proportion of SLE patients at 5 year. Patients with more SLE renal flares and had received more immunosuppression were more likely to have sero-reversion of the anti-HPV antibodies.Clinical trial registration number: US ClinicalTrials.gov (NCT00911521 & NCT02477254).



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Impact of rotavirus vaccine on diarrheal hospitalization and outpatient consultations in the Philippines: First evidence from a middle-income Asian country

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Anna Lena Lopez, Peter Francis Raguindin, Joel Esparagoza, Kimberley Fox, Nyambat Batmunkh, Joseph Bonifacio, Umesh D. Parashar, Jacqueline E. Tate, Maria Joyce Ducusin
BackgroundMonovalent rotavirus (RV) vaccine was introduced in the Philippines in a phased manner beginning in 2012. To assess the impact of RV vaccine, we conducted a retrospective review of diarrheal admissions in two hospitals.MethodsRecords of physician-diagnosed diarrheal admissions were reviewed in D.O. Plaza Hospital (DOPH) from 2009 to 2016 in Agusan del Sur where RV vaccine was introduced in the immunization program; and in Cotabato Regional Medical Center (CRMC) from 2011 to 2016 in a region where the vaccine was not introduced. Reports from consultations in public health clinics in Agusan Del Sur and RV vaccine coverage were obtained.ResultsAll-cause diarrheal admissions among children <5 years old in DOPH declined from 2013 to 2016 following RV vaccine introduction in 2012. Using the 2009–2011 mean number of hospitalizations as baseline (X‾ = 1,141), the reductions were 28% (n = 821), 56% (n = 507), 63% (n = 417) and 59% (n = 466) in 2013, 2014, 2015 and 2016, respectively. In comparison, no substantial declines in diarrheal hospitalizations were seen in CRMC from 2011 to 2016. A declining trend was also seen in outpatient consultations in Agusan del Sur following RV vaccine introduction with declines of 27% (n = 2,333), 33% (n = 2,143), 45% (n = 1,764) and 67% (n = 1,059) in 2013, 2014, 2015 and 2016. From September 2012 to December 2016, the 1 and 2-dose RV vaccine coverage gradually increased from 5% and 4% in 2012 to 92% and 88% in 2015, but decreased in 2016 to 53% and 52%, respectively.DiscussionRV vaccine introduction was associated with a substantial decline in diarrheal hospitalizations and outpatient consultations for diarrhea in Agusan del Sur, Philippines.



https://ift.tt/2InUnKX

Identifying ways to increase seasonal influenza vaccine uptake among pregnant women in China: A qualitative investigation of pregnant women and their obstetricians

Publication date: 31 May 2018
Source:Vaccine, Volume 36, Issue 23
Author(s): Richun Li, Ruiqian Xie, Chong Yang, Jeanette Rainey, Ying Song, Carolyn Greene
BackgroundPregnant women are at higher risk for complications from influenza infection. Nevertheless, seasonal influenza vaccination among pregnant women in China is low. A better understanding of perceptions of pregnant women and their physicians, and factors influencing decisions about receiving seasonal influenza vaccine could be used to develop effective strategies for improving seasonal influenza vaccine uptake during pregnancy.MethodsWe recruited pregnant women from 9 hospitals located in 5 cities across China to participate in focus group interviews. Obstetricians from the same hospitals were recruited for one on one in-depth interviews. We collected information about perceptions of barriers and motivating factors for utilizing seasonal influenza vaccine during pregnancy. We systematically analyzed the information using qualitative methods.ResultsWe conducted 18 focus groups with 108 pregnant women and interviewed 18 obstetricians. Awareness about the use of influenza vaccine during pregnancy was minimal in both subject groups. None of the pregnant women had received influenza vaccine during pregnancy and none of the obstetricians had recommended influenza vaccine for their patients. Both groups noted insufficient knowledge about influenza infection and benefits of the vaccine, concerns about vaccine safety, and lack of local data related to vaccine use in Chinese pregnant women. Obstetricians cited the lack of a national policy as a major barrier to recommending seasonal influenza vaccine to pregnant women. Pregnant women cited not receiving a recommendation for vaccination from healthcare workers as an additional barrier.ConclusionOur findings highlight the immediate need to increase awareness and knowledge about the risks of influenza infection and the benefits and safety of seasonal influenza vaccination among both pregnant women and obstetricians in China. Obstetricians interviewed stated that the development and implementation of a national policy prioritizing pregnant women for seasonal influenza vaccination would facilitate their willingness to recommend seasonal influenza vaccine to pregnant women.



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Weight-Loss Cognitive-Behavioural Treatment and Essential Amino Acid Supplementation in a Patient with Spinal Muscular Atrophy and Obesity

Spinal muscular atrophy is a genetic neuromuscular disease characterised by muscle atrophy, hypotonia, weakness, and progressive paralysis. Usually, these patients display increased fat mass deposition and reductions in fat-free mass and resting energy expenditure—an unfavourable condition that facilitates the development of obesity. However, weight management of these patients remains poorly described. Hence, the aim of this case report was to describe the clinical presentation and weight management of a 31-year-old male patient with spinal muscular atrophy type III, class I obesity, and metabolic syndrome treated for 1 year by means of a personalised multistep cognitive-behavioural treatment for obesity. The treatment produced a weight loss of 7.2 kg (7.1%), which was associated with a marked improvement in both the patient's self-reported general conditions and obesity-related cardiometabolic profile, and no adverse effects in terms of spinal muscular atrophy (i.e., reductions in fat-free mass or resting energy expenditure).

https://ift.tt/2rMbcVL

Immune Factors in Deep Vein Thrombosis Initiation

Publication date: Available online 16 May 2018
Source:Trends in Immunology
Author(s): Ivan Budnik, Alexander Brill
Deep vein thrombosis (DVT) is a major origin of morbidity and mortality. While DVT has long been considered as blood coagulation disorder, several recent lines of evidence demonstrate that immune cells and inflammatory processes are involved in DVT initiation. Here, we discuss these mechanisms, in particular, the role of immune cells in endothelial activation, and the immune cascades leading to expression of adhesion receptors on endothelial cells. We analyze the specific recruitment and functional roles of different immune cells, such as mast cells and leukocytes, in DVT. Importantly, we also speculate how immune modulation could be used for DVT prevention with a lower risk of bleeding complications than conventional therapeutic approaches.



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Humans Are Visual Experts at Unfamiliar Face Recognition

Publication date: June 2018
Source:Trends in Cognitive Sciences, Volume 22, Issue 6
Author(s): Bruno Rossion




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What We See in Unfamiliar Faces: A Response to Rossion

Publication date: June 2018
Source:Trends in Cognitive Sciences, Volume 22, Issue 6
Author(s): Andrew W. Young, A. Mike Burton




https://ift.tt/2KvS5pT

Mind-Wandering as a Natural Kind: A Family-Resemblances View

Publication date: June 2018
Source:Trends in Cognitive Sciences, Volume 22, Issue 6
Author(s): Paul Seli, Michael J. Kane, Jonathan Smallwood, Daniel L. Schacter, David Maillet, Jonathan W. Schooler, Daniel Smilek
As empirical research on mind-wandering accelerates, we draw attention to an emerging trend in how mind-wandering is conceptualized. Previously articulated definitions of mind-wandering differ from each other in important ways, yet they also maintain overlapping characteristics. This conceptual structure suggests that mind-wandering is best considered from a family-resemblances perspective, which entails treating it as a graded, heterogeneous construct and clearly measuring and describing the specific aspect(s) of mind-wandering that researchers are investigating. We believe that adopting this family-resemblances approach will increase conceptual and methodological connections among related phenomena in the mind-wandering family and encourage a more nuanced and precise understanding of the many varieties of mind-wandering.



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Editors, Contents, Cover details

Publication date: June 2018
Source:Trends in Cognitive Sciences, Volume 22, Issue 6





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How Memory Replay in Sleep Boosts Creative Problem-Solving

Publication date: June 2018
Source:Trends in Cognitive Sciences, Volume 22, Issue 6
Author(s): Penelope A. Lewis, Günther Knoblich, Gina Poe
Creative thought relies on the reorganisation of existing knowledge. Sleep is known to be important for creative thinking, but there is a debate about which sleep stage is most relevant, and why. We address this issue by proposing that rapid eye movement sleep, or 'REM', and non-REM sleep facilitate creativity in different ways. Memory replay mechanisms in non-REM can abstract rules from corpuses of learned information, while replay in REM may promote novel associations. We propose that the iterative interleaving of REM and non-REM across a night boosts the formation of complex knowledge frameworks, and allows these frameworks to be restructured, thus facilitating creative thought. We outline a hypothetical computational model which will allow explicit testing of these hypotheses.



https://ift.tt/2INcqtv

Facile preparation of nitrogen and sulfur co-doped graphene-based aerogel for simultaneous removal of Cd 2+ and organic dyes

Abstract

The need in simultaneous removal of heavy metals and organic compounds dictates the development of synthetic adsorbents with tailor-made properties. A nitrogen (N) and sulfur (S) co-doped graphene-based aerogel (GBA) modified with 2,5-dithiobisurea was synthesized hydrothermally for simultaneous adsorption of Cd²⁺ and organic dyes—safranin-O (SO), crystal violet (CV), and methylene blue (MB). 2,5-Dithiobisurea was used as nitrogen and sulfur sources to introduce N and S-containing functional group onto graphene oxide. The adsorption mechanism of GBA towards Cd²⁺ and organic dyes was studied by Dumwald-Wagner models and the results showed that surface and intraparticle diffusion was the key factor in controlling the rate of adsorption. The maximum adsorption capacities of GBA towards Cd²⁺, SO, CV, and MB comprised 1.755, 0.949, 0.538, and 0.389 mmol/g in monocomponent system, respectively. Adsorption synergism was observed with respect to Cd²⁺ in presence of the dyes. The performance of GBA with respect to Cd²⁺ removal from binary solutions, Cd²⁺-SO, Cd²⁺-CV, and Cd²⁺-MB, was enhanced by the presence of the dyes significantly, while the adsorption capacities towards the dyes were not affected by the presence of Cd²⁺.

https://ift.tt/2IK48m5

Degradation of ampicillin antibiotic by electrochemical processes: evaluation of antimicrobial activity of treated water

Abstract

Ampicillin (AMP) is an antibiotic widely used in hospitals and veterinary clinics around the world for treating infections caused by bacteria. Therefore, it is common to find traces of this antibiotic in wastewater from these entities. In this work, we studied the mineralization of this antibiotic in solution as well as the elimination of its antimicrobial activity by comparing different electrochemical advanced oxidation processes (EAOPs), namely electro-oxidation with hydrogen peroxide (EO-H₂O₂), electro-Fenton (EF), and photo electro-Fenton (PEF). With PEF process, a high degradation, mineralization, and complete elimination of antimicrobial activity were achieved in 120-min electrolysis with high efficiency. In the PEF process, fast mineralization rate is caused by hydroxyl radicals (·OH) that are generated in the bulk, on the anode surface, by UV radiation, and most importantly, by the direct photolysis of complexes formed between Fe³⁺ and some organic intermediates. Moreover, some products and intermediates formed during the degradation of the antibiotic Ampicillin, such as inorganic ions, carboxylic acids, and aromatic compounds, were determined by photometric and chromatographic methods. An oxidation pathway is proposed for the complete conversion to CO₂.

https://ift.tt/2KwdxuS

Distal Nerve Transfers: A Perspective on the Future of Reconstructive Microsurgery

J reconstr Microsurg
DOI: 10.1055/s-0038-1656719

Background Nerve transfer can be broadly separated into two categories: proximal nerve graft and/or transfer and distal nerve transfer. The superiority of proximal nerve graft/transfer over distal nerve transfer strategy has been debated extensively, but which strategy is the best has not yet been defined. Each technique has its own advantages and disadvantages. However, proximal nerve graft/transfer is still the main reconstructive procedure based on the principle of "no diagnosis, then no treatment." Proximal nerve transfer can avoid iatrogenic injury where the lesion is still in continuity and neurolysis is the only procedure without further cutting the nerve. Results Our clinical and experimental study show that proximal nerve grafts/transfers yield at least equal or better results compared to distal nerve transfers. Proximal nerve grafts/transfers remain the mainstay of my reconstructive strategy. Proximal nerve graft/transfer offers more accurate diagnosis and proper treatment to restore shoulder and elbow functions simultaneously. Distal nerve transfers can offer more efficient elbow flexion. Conclusion Combined, both strategies in primary nerve reconstruction are especially recommended when there is no healthy or not enough donor nerve available Distal nerve transfers should be considered as a complementary option for proximal nerve grafts/ transfers.
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Lower Extremity Limb Salvage with Cross Leg Pedicle Flap, Cross Leg Free Flap, and Cross Leg Vascular Cable Bridge Flap

J reconstr Microsurg
DOI: 10.1055/s-0038-1641712

Background Lower extremity salvage following significant soft tissue loss can be complicated by lack of recipient vessel for free tissue transfer. We describe our experience in lower limb salvage for patients with no recipient vessels with the use of pedicle, free and cable bridge flaps. Methods A retrospective review from 1985 to 2017 of patients undergoing lower limb salvage using a contralateral pedicle cross leg (PCL) flaps, free cross leg (FCL) flaps, or free cable bridge (FCB) flaps was conducted. Demographics, etiology of the reconstruction, type of flap used, donor-site vessels, defect size, operating time, time of pedicle division, length of hospital stay, time to ambulation, and complications were analyzed. Results A total of 53 patients (48 males and 5 females) with an average age of 35 years (range, 29–38 years) were identified. The etiology for the reconstruction was trauma in 52 patients and oncological resection in 1 patient. There were 18 PCL, 25 FCL, and 10 FCB completed. The recipient vessels for all flaps were the posterior tibial artery and vein. The average operating room times for PCL, FCL, and FCB flaps were 4, 9, and 10 hours, respectively. The average length of hospital stay was 5 weeks and average time to ambulation was 4 weeks. The average follow-up time was 7.5 years (range, 3–12 years). Complications encountered were hematoma (six), prolonged pain (six), total flap loss (two), reoperation (five), and infection (four). Limb salvage rates were 96.2%. Conclusion When ipsilateral limb vessels are not available, and other reconstructive options have been exhausted, cross leg flaps can be a viable option for limb salvage in the setting of extensive defects.
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Rhinocerebrale Mucormykose

Laryngo-Rhino-Otol
DOI: 10.1055/a-0619-5143

Mucormykose ist eine Schimmelpilzinfektion, die insbesondere bei immunsupprimierten Patienten rasch progredient verlaufen kann. Uns wurde eine 47-jährige Patientin mit einer Ptosis links bei sonst unauffälligem augenärztlichen Befund vorgestellt. Die Blutzuckerwerte waren bei Diabetes mellitus deutlich erhöht.Das CT der Nasennebenhöhlen zeigte eine moderate Verlegung des Siebbeins links und in der cMRT erschienen der orbitale Fettkörper und die Augenmuskeln verdickt. Als noch eine Hebungseinschränkung des Bulbus auftrat, erfolgte die Nasennebenhöhlenoperation. Mikrobiologisch wurde dabei eine Mucormykose (Gattung Lichtheimia) gesichert. Die Patientin erblindete links, sodass die Indikation zur Exenteratio orbitae links und Re-Pansinusoperation zur Fokussanierung gestellt wurde. Liposomales Amphotericin B und Posaconazol wurden hochdosiert verabreicht und der Blutzucker wurde streng reguliert. Bei bildmorphologischem Progress waren weitere operative Eingriffe bis zur Duraresektion nötig.Der Verlauf war durch Komplikationen (rezidivierende septische Episoden, Niereninsuffizienz, ein bifrontales Epiduralhämatom sowie multiple zerebrale Mikroinfarkte) erschwert, doch schlussendlich konnte sie nach 8-monatiger Hospitalisation entlassen werden. Eine Epithese wurde angepasst und sie ist seit 24 Monaten (nach Diagnose) rezidivfrei.
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Die Rolle der elektiven Neck dissection bei Salvage Laryngektomie – eine retrospektive Analyse

Laryngo-Rhino-Otol
DOI: 10.1055/a-0619-5388

Im Rahmen der Salvage Laryngektomie (SLE) bei Rezidivkarzinomen des Larynx und Hypopharynx wird häufig, wie bei der primären Laryngektomie (LE), eine elektive beidseitige Neck dissection durchgeführt. Der therapeutische Nutzen muss angesichts des potentiell höheren Morbiditätsrisikos nach definitiver Radiochemotherapie gegenüber den Risiken abgewogen werden.In einer retrospektiven Analyse wurden onkologische Parameter von Patienten erfasst, welche bei Rezidivkarzinomen des Larynx und Hypopharynx nach primärer Radiochemotherapie eine SLE mit beidseitiger Neck dissection erhielten. Zum Vergleich wurden Daten von Patienten mit primärer LE und beidseitiger Neck dissection bei Larynx- und Hypopharynxkarzinomen erfasst.19 Patienten mit SLE und 83 Patienten mit LE wurden in die Analyse eingeschlossen. Bei der Mehrzahl der Patienten waren sowohl das initiale Tumorstadium als auch das Rezidiv-Tumorstadium vor SLE fortgeschritten. Vor SLE wiesen 5 % der Patienten (n = 1) klinisch metastasensuspekte Lymphknoten auf, vor LE 47 % (n = 39). Bei 17 % (n = 14) der Patienten mit LE wurden okkulte Lymphknotenmetastasen nachgewiesen, bei SLE lediglich bei 5 % der Patienten (n = 1). Insgesamt ergab sich ein pN+ -Stadium in 55 % (LE, n = 44) bzw. 10 % (SLE, n = 2) der Fälle. Die Gesamtzahl der entfernten Lymphknoten bei LE war höher als bei SLE (37,3 vs. 18,7, p < 0,001). Das 5-Jahres-Gesamtüberleben der Patienten lag nach LE bei 50,0 %, nach SLE bei 33,3 %.Patienten, welche bei Rezidivkarzinomen des Larynx oder Hypopharynx nach primärer Bestrahlung eine SLE erhalten, weisen selten Lymphknotenmetastasen auf. Dennoch kommt es in Einzelfällen zu einer okkulten Metastasierung. Bei der Planung der letzten kurativen Therapieoption sollte dies in Betracht gezogen werden.
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