Raising Awareness of Graves’ Orbitopathy with Early Warning Cards

Abstract

Background

Clinically significant Graves' orbitopathy (GO) develops in about 25% of those with Graves' disease (GD); most cases of GD in the UK are managed by endocrinologists. Despite this, patients report significant delays before a diagnosis of GO is made. Measures to increase awareness of the early signs of GO and establishing a fast-track referral pathway to specialist care should overcome these delays and potentially improve outcomes.

Aims

We aimed to determine whether issuing a "GO early warning card" to all GD patients raises awareness of GO and facilitates early diagnosis, what percentage of cards result in a telephone contact, the number of "false reports" from card carriers and patient perceptions of the cards.

Methods

We designed cards, detailing common GO symptoms and a telephone number for patients developing symptoms. Cards were distributed to 160 GD patients, without known GO, attending four endocrine clinics in the UK (December 2015 - March 2016). We recorded telephone contacts over twelve months from when the last card was distributed and gathered patient feedback.

Results

The early warning cards were well received by patients in general. Over twelve months, ten telephone contacts from nine patients, all related to ocular symptoms, were received (6% of cards issued). Nine calls resulted in an additional clinic review (for eight patients) and four diagnoses of GO were made.

Conclusions

This pilot study demonstrates that it is feasible to distribute GO early warning cards in clinic and that they can be used to facilitate an early diagnosis of GO.

This article is protected by copyright. All rights reserved.

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A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma

Summary

Background

Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis as well as cell status like metabolism changes in distant metastatic tumors have not been clearly elucidated.

Objective

To identify serum metabolic signature of distant metastatic PTC.

Design, patients and measurementsIn

this study, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA)scores plots were used to analyze the data.

Results

PCA and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed 'alanine, aspartate and glutamate metabolism' and 'inositol phosphate metabolism' were the most relevant pathways.

Conclusion

Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biologic behaviors of tumor cells including proliferation, invasion/migration, and immune escape. Diet/gut microbiota produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding to the distant metastasis of PTC as well as potential adjuvant therapy targets.

This article is protected by copyright. All rights reserved.

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Sarcoid-like granulomas in renal cell carcinoma: The Houston Methodist Hospital experience

Publication date: Available online 29 July 2017
Source:Annals of Diagnostic Pathology
Author(s): Komal Arora, Mukul K. Divatia, Luan Truong, Steven S. Shen, Alberto G. Ayala, Jae Y. Ro
Sarcoid-like (SL) granulomas have been previously described in association with malignant tumors. These granulomas appear to be tumor-related but are not indicative of systemic sarcoidosis, and hence are referred to as SL reactions. These SL reactions can be seen within the primary tumor, its vicinity, or in uninvolved sites such as the spleen, bone marrow, skin, and/or regional lymph nodes draining the tumor. It is a widely held view that SL granulomas are caused by soluble antigenic factors, shed by tumor cells or released due to tumor necrosis. SL reactions reported in Hodgkin lymphoma have been associated with a better prognosis. SL granulomas are thought to play an important role in the host's defenses against metastatic extension. SL granulomas have been reported in approximately 4.4% of carcinomas. Isolated cases of renal cell carcinoma (RCC) with SL granulomas have been reported with questionable prognostic significance. We identified 11 cases of RCCs with SL granulomas. Interestingly, all cases had abundant clear cell cytoplasm (10 clear cell RCC cases and 1 clear cell papillary RCC). We propose that this clear, abundant cytoplasm of the tumor cells with high content of glycogen and lipids may trigger granuloma formation akin to that seen in seminomas with SL granulomas. To date, this is the largest case series of RCCs with SL granulomas.



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Editorial Board

Publication date: October 2017
Source:Medical Image Analysis, Volume 41





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Editorial Board

Publication date: August 2017
Source:Medical Image Analysis, Volume 40





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New methods for the geometrical analysis of tubular organs

Publication date: Available online 29 July 2017
Source:Medical Image Analysis
Author(s): Florent Grélard, Fabien Baldacci, Anne Vialard, Jean-Philippe Domenger
This paper presents new methods to study the shape of tubular organs. Determining precise cross-sections is of major importance to perform geometrical measurements, such as diameter, wall-thickness estimation or area measurement. Our first contribution is a robust method to estimate orthogonal planes based on the Voronoi Covariance Measure. Our method is not relying on a curve-skeleton computation beforehand. This means our orthogonal plane estimator can be used either on the skeleton or on the volume. Another important step towards tubular organ characterization is achieved through curve-skeletonization, as skeletons allow to compare two tubular organs, and to perform virtual endoscopy. Our second contribution is dedicated to correcting common defects of the skeleton by new pruning and recentering methods. Finally, we propose a new method for curve-skeleton extraction. Various results are shown on different types of segmented tubular organs, such as neurons, airway-tree and blood vessels.

Graphical abstract

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d-Tyrosyl-tRNA Deacylase: A New Function

Publication date: Available online 29 July 2017
Source:Trends in Biochemical Sciences
Author(s): Richard Calendar
d-Aminoacyl-tRNA deacylase (DTD) hydrolyzes d-amino acids mistakenly attached to tRNAs and, thus, has been implicated in perpetuating protein homochirality. Fifty years after the discovery of DTD, it has now been shown that its function extends beyond 'chiral proofreading' because it also eliminates glycine that has been erroneously coupled to tRNA^Ala.



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The potential of proton therapy to reduce acute haematological toxicity in concurrent chemoradiotherapy for oesophageal cancer

Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Samantha Warren, Christopher N. Hurt, Thomas Crosby, Mike Partridge, Maria A. Hawkins
Radiotherapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy, we therefore investigated the potential of bone marrow sparing with protons for oesophageal tumours.21 mid-oesophageal cancer patients treated with conformal radiotherapy (3D50) were selected. Two surrogates for bone marrow were created by outlining thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse (Varian). The % overlap of TV with the PTV was recorded for each patient. Additional plans were created retrospectively: a volumetric modulated arctherapy plan (VMAT50) with the same dose as 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high risk sub-region within the planning treatment volume (VMAT62.5); a re-optimised TV sparing VMAT plan (VMAT62.5bm) and a proton therapy plan (SFO62.5) with the same SIB dose prescription. Bone and TV dose-metrics were recorded and compared across all plans and variation with respect to PTV size and % overlap for each patient was studied.3D50 plans show the highest bone mean dose and TV V30Gy values for each patient. VMAT plans irradiate a larger bone V10Gy volume than 3D50 plans. Re-optimised VMAT62.5bm plans showed improved sparing of the TV volume, but only proton plans showed significant sparing for bone V10Gy and bone mean dose, especially for patients with larger PTV size.

Teaser

Radiotherapy dose escalation is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. We investigated the bone marrow dose of VMAT, proton plans, and marrow-sparing VMAT plans for oesophageal tumours. Improved marrow sparing was possible with VMAT, but only protons showed significant sparing for bone V10Gy and bone mean dose, especially for patients with larger PTV size.


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Reirradiation for Recurrent Pediatric CNS Malignancies: A Multi-Institutional Review

Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Avani D. Rao, Arif Rashid, Qinyu Chen, Rosangela C. Villar, Daria Kobyzeva, Kristina Nilsson, Karin Dieckmann, Alexey Nechesnyuk, Ralph Ermoian, Sara Alcorn, Shannon M. MacDonald, Matthew M. Ladra, Eric C. Ford, Brian A. Winey, Maria Luisa S. Figueiredo, Michael J. Chen, Stephanie A. Terezakis
PurposeReirradiation has been proposed as an effective modality for recurrent CNS malignancies for adults. We evaluated toxicity and outcomes of CNS reirradiation in pediatric patients.Methods and MaterialsPediatric patients age <21 years at time of initial diagnosis who developed a recurrent CNS malignancy treated with repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed.ResultsSixty-seven pediatric patients were treated with CNS reirradiation. Primary diagnoses included medulloblastoma/primitive neuroendocrine tumor (n=20, 30%), ependymoma (n=19, 28%), germ cell tumor (n=8, 12%), high grade glioma (n=9, 13%), low grade glioma (n=5, 7%), and other (n=6, 9%). Median age at first course of RT was 8.5 years (range:0.5-19.5 years) and 12.3 years (range:3.3-30.2 years) at time of reirradiation. The median time interval between RT courses was 2.0 years (range: 0.3-16.5). Median dose and fractionation of RT in equivalent 2 Gy fractions (EQD2) was 63.7 Gy (range 27.6-74.8 Gy) for initial RT and 53.1 Gy (range 18.6-70.1 Gy) for repeat RT. Location of relapse was infield in 52 patients (78%) and surrounding initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross- or sub-total resection at time of recurrence. Techniques for reirradiation were IMRT (n=46), 3D-CRT (n=9), SRS (n=4, 12-13Gyx1 or 5 Gyx5), protons (n=4), combined modality (n=3), 2D-RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 cases after first course of RT and 1 additional patient after reirradiation. Six patients (9%) experienced secondary neoplasms following initial RT (1 hematologic, 5 intracranial neoplasms). One patient developed a secondary neoplasm identified shortly after repeat RT. Median overall survival following end of reirradiation was 12.8 months in the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma following reirradiation.ConclusionsCNS reirradiation in pediatric patients may be a reasonable treatment option with moderate survival noted following repeat RT; although, prospective data characterizing rates of local control and toxicity are needed.

Teaser

This is a unique study evaluating the treatment parameters, toxicity, and outcomes of pediatric CNS reirradiation through a multi-national, multi-institutional pediatric research consortium. Low rates of radiation necrosis were observed and patients experienced reasonable survival rates following repeat radiation therapy to recurrent CNS tumors that may justify the risks of reirradiation.


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Hamartome conjonctif étendu de l’enfant

Publication date: Available online 29 July 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Lafargue, S. Fraitag, O. Boccara, F. Comoz, J. Rod, C. Turgis Mezerette, A. Dompmartin
IntroductionL'hamartome conjonctif (HC) est une anomalie rare des composants de la matrice extracellulaire qui se présente habituellement sous la forme de papules couleur de peau normale. Cette atteinte peut être syndromique ou sporadique.ObservationsNous rapportons deux cas d'HC isolés de l'enfant, très étendus et infiltrants, qui entraînaient un risque d'enraidissement articulaire. Il s'agissait d'un hamartome mixte et d'un collagénome.DiscussionIl est difficile de dater l'apparition de ces lésions qui passent souvent inaperçues au début. Devant un HC étendu, les principaux diagnostics différentiels à éliminer grâce à la biopsie cutanée sont la fasciite à éosinophiles et la morphée. L'HC peut être associé à des lésions d'osteopœcilie dans le syndrome de Buschke-Ollendorf, à rechercher par un bilan radiologique itératif. La prise en charge est symptomatique.BackgroundConnective tissue nevus (CTN) is a rare condition of the extracellular matrix components that generally presents as papulae of normal skin colour. This condition may be syndromic or sporadic.Patients and methodsWe report herein two isolated cases of extensive and infiltrative CTN in children at risk for subsequent joint stiffening. The pathology samples displayed respectively mixed hamartoma and a collagenoma.DiscussionThe onset of these lesions is often difficult to establish, since they are usually unnoticeable at first. When confronted with extensive CTN, the main differential diagnoses are eosinophilic fasciitis and morphea, and these must be ruled out by skin biopsy. CTN is associated with osteopoikilosis in Buschke-Ollendorf syndrome. Skeletal lesions are asymptomatic and are detected by means of iterative X-ray. Their management comprises symptomatic care.



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Hypersensibilité aux sels de platine et aux taxanes : intérêt des tests cutanés et des inductions de tolérance

Publication date: Available online 29 July 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): F. Brault, J. Waton, C. Poreaux, J.-L. Schmutz, A. Barbaud
ButLes réactions d'hypersensibilité (HS) aux sels de platine (SP) et aux taxanes (TX) sont fréquentes. L'objectif de notre étude était d'évaluer l'intérêt des tests cutanés et des inductions de tolérance aux SP et TX.MéthodesIl s'agit d'une étude rétrospective réalisée entre janvier 2007 et février 2016, incluant les patients adressés pour suspicion d'HS immédiate ou retardée. Les tests cutanés, prick tests (pT) et intradermoréaction (IDR), étaient réalisés selon les recommandations de l'ENDA/EAACI et les inductions de tolérance (IT) selon un protocole en 12 paliers.RésultatsChez les 99 patients inclus (30 hommes, 69 femmes, âge moyen 60,4 ans), les SP étaient suspectés chez 86 et les TX chez 13. Les tests cutanés étaient positifs chez 25 patients (7 pT et 18 IDR), 23 avec les SP et 2 avec les TX. Une IT était proposée chez 50 patients, réalisée chez 33 (30 avec SP et 3 avec TX), bien supportée chez 29, nécessitant une adaptation chez 7 mais échouait chez 4 patients. Chez ces 4 derniers, les tests cutanés étaient positifs. Parmi les patients ayant des tests positifs à l'oxaliplatine, 75 % avaient une réaction d'HS lors de l'IT, soit une proportion deux fois plus grande que parmi les patients ayant des tests cutanés négatifs. Des réactions croisées survenaient dans 2 % des cas avec les SP et 7 % avec les TX.ConclusionCette expérience française confirme l'intérêt des IT en 12 étapes, permettant dans la plupart des cas de poursuivre une chimiothérapie chez un patient avec HS. Les tests cutanés sont utiles pour l'étude des réactions croisées, cependant leur réalisation doit être considérée au cas par cas.AimThe rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization.Patients and methodsThis was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization.ResultsAmong the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity.ConclusionThis French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history.



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Strategies for Decreasing Screening Mammography Recall Rates While Maintaining Performance Metrics

Publication date: Available online 29 July 2017
Source:Academic Radiology
Author(s): Lisa A. Mullen, Babita Panigrahi, Jacqueline Hollada, Benita Panigrahi, Eniola T. Falomo, Susan C. Harvey
Rationale and ObjectiveThis study aimed to determine the impact of interventions designed to reduce screening mammography recall rates on screening performance metrics.Materials and MethodsWe assessed baseline performance for full-field digital mammography (FFDM) and digital breast tomosynthesis mammography (DBT) for a 3-year period before intervention. The first intervention sought to increase awareness of recalls from screening mammography. Breast imagers discussed their perceptions regarding screening recalls and were required to review their own recalled cases, including outcomes of diagnostic evaluation and biopsy. The second intervention implemented consensus double reading of all recalls, requiring two radiologists to agree if recall was necessary. Recall rates, cancer detection rates, and positive predictive value 1 (PPV1) were compared before and after each intervention.ResultsThe baseline recall rate, cancer detection rate, and PPV1 were 11.1%, 3.8/1000, and 3.4%, respectively, for FFDM, and 7.6%, 4.8/1000, and 6.0%, respectively, for DBT. Recall rates decreased significantly to 9.2% for FFDM and to 6.6% for DBT after the first intervention promoting awareness, as well as to 9.9% for FFDM after the second intervention implementing group consensus. PPV1 increased significantly to 5.7% for FFDM and to 9.0% for DBT after the second intervention. Cancer detection rate did not significantly change with the implementation of these interventions. An average of 2.3 minutes was spent consulting for each recall.ConclusionReduction in recall rates is desirable, provided performance metrics remain favorable. Our interventions improved performance and could be implemented in other breast imaging settings.



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Does the Oral “Mock Board” Examination Still Have a Role as a Training Tool?

Publication date: Available online 29 July 2017
Source:Academic Radiology
Author(s): Colin Strickland, Alexandria Jensen, Tatum McArthur
Rationale and ObjectivesThe American Board of Radiology has adopted a new standardized board examination and the traditional oral examination has been abandoned. Although many programs have changed their educational efforts to reflect the new test format, some faculty members and residents have expressed a desire to keep an oral examination as a component of education and evaluation in radiology residency programs.Materials and MethodsAn oral comprehensive examination including all the appropriate subspecialties was administered to each second year and third year resident in our training program by faculty members. Both the resident examinees and faculty examiners were surveyed after the examination to gauge the perceived value of the experience.ResultsResidents were divided in their perceptions of the fairness and utility of an oral examination as a tool to aid in board preparation and as an assessment of their knowledge and communication skill. Faculty members were universal in their endorsement of the oral examination and suggested continued use of the technique.ConclusionsResidents and faculty members have differing perceptions of an oral examination delivered during training to assess knowledge and communication skill. The value of an oral examination in providing actionable feedback to trainees and the possibility of detecting struggling residents made it useful in our training program, and it thus it has been implemented for future years. Whether resident performance measured by this technique is predictive of success on American Board of Radiology examinations remains unclear.



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The Addition of Automated Breast Ultrasound to Mammography in Breast Cancer Screening Decreases Stage at Diagnosis

Publication date: Available online 29 July 2017
Source:Academic Radiology
Author(s): Ian Grady, Nailya Chanisheva, Tony Vasquez
Rationale and ObjectivesThis study aimed to determine the best screening strategy using automated whole-breast ultrasound and mammography in women with increased breast density or an elevated risk of breast cancer.Materials and MethodsAfter an institutional review board waiver was obtained, a retrospective review of 122 cancer cases diagnosed in 3435 women with increased breast density or an elevated risk of breast cancer, screened with mammography and supplemental automated whole-breast ultrasound, was performed. The imaging modality on which each cancer was seen was noted. Screening strategies were postulated.For each screening strategy, rates of advanced cancer diagnosis, with 95% confidence limits, are calculated using the Clopper-Pearson method. Differences in outcomes were calculated using Cochrane Q test and McNemar test for paired observations. Results were expressed for all stages of cancer and for invasive cancers only.ResultsWhen all cancer stages are considered, mammographic screening reduces advanced cancers by 31% over no screening. Ultrasound-only screening results in a 32% reduction. The combination of mammographic and ultrasound screening reduces advanced cancers by 40% (P < .05).Compared to mammographic screening, mammographic plus ultrasound screening reduces advanced-stage cancers by 5.7% (P = 0.03) for all stages and 10.8% (P = 0.02) for invasive cancers.ConclusionsFor women with increased breast density or who are at high risk of developing breast cancer, a combination of screening mammography and whole-breast automated ultrasound is superior to mammographic screening. Screening ultrasound alone is also an effective screening strategy.



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Auditory Dysfunction in Patients with Huntington’s Disease

Publication date: Available online 29 July 2017
Source:Clinical Neurophysiology
Author(s): Oliver Profant, Jan Roth, Zbyněk Bureš, Zuzana Balogová, Irena Lišková, Jan Betka, Josef Syka
ObjectiveHuntingtońs disease (HD) is an autosomal, dominantly inherited, neurodegenerative disease. The main clinical features are motor impairment, progressive cognitive deterioration and behavioral changes. The aim of our study was to find out whether patients with HD suffer from disorders of the auditory system.MethodsA group of 17 genetically verified patients (11 males, 6 females) with various stages of HD (examined by UHDRS – motor part and total functional capacity, MMSE for cognitive functions) underwent an audiological examination (high frequency pure tone audiometry, otoacoustic emissions, speech audiometry, speech audiometry in babble noise, auditory brainstem responses). Additionally, 5 patients underwent a more extensive audiological examination, focused on central auditory processing. The results were compared with a group of age-matched healthy volunteers.ResultsOur results show that HD patients have physiologic hearing thresholds, otoacoustic emissions and auditory brainstem responses; however, they display a significant decrease in speech understanding, especially under demanding conditions (speech in noise) compared to age-matched controls. Additional auditory tests also show deficits in sound source localization, based on temporal and intensity cues. We also observed a statistically significant correlation between the perception of speech in noise, and motoric and cognitive functions. However, a correlation between genetic predisposition (number of triplets) and function of inner ear was not found.ConclusionsWe conclude that HD negatively influences the function of the central part of the auditory system at cortical and subcortical levels, altering predominantly speech processing and sound source lateralization.SignificanceWe have thoroughly characterized auditory pathology in patients with HD that suggests involvement of central auditory and cognitive areas.



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Benevolent personification of the MoH increases compliance with an emergency polio vaccination

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Golan Shahar, Gal Noyman-Veksler, Shai Itamar, David Greenberg, Itamar Grotto
ObjectiveParental compliance is crucial to the success of mass vaccination campaigns targeting children. Relying on psychological/neuroscientific research concerning the role of personification (i.e., viewing the inanimate as human) in behavior, the authors examined the effect of parents' personification of the Israeli Ministry of Health (MoH) on compliance with a publicly controversial mass vaccination campaign, which was aimed at stopping the spread of a wild poliovirus.MethodsParticipants were 555 parents of children aged 9 or younger, residing in the center/north of Israel, an area covered by Phase 2 of the campaign. T1 assessment, employed two days prior to Phase 2, tapped into demographics, attitudes towards vaccination, intent to comply, and a benevolent personification of the MoH (i.e., "The MoH is caring") vs. a malevolent personification of the MoH ("The MoH is hysteric"). T2 assessment, transpiring four months after the end of the campaign, addressed presence and reasons for (non-)compliance.ResultsThe study's overall compliance rate was 61.8%. The principal reason for compliance was "adherence to the recommendations of the MoH" (68.49%). In a multivariate logistic regression analysis, prospective predictors of compliance were: an early intent to comply (O.R.=2.56, p=0.000), being male (O. R.=1.51, p=0.023), and a benevolent personification of the MoH (O.R.=1.21, p=0.019).ConclusionParents who experienced the Israeli MoH as a benevolent protagonist were more likely to comply with the mass vaccination campaign. Findings highlight the role of leadership in public health campaigns during emergencies.



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Macrophage-derived insulin-like growth factor-1 affects influenza vaccine efficacy through the regulation of immune cell homeostasis

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Il-Sub Yoon, Hyelim Park, Hye-Won Kwak, Yong Woo Jung, Jae-Hwan Nam
The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice showed a relatively weak booster effect of repeated immunization. In contrast, antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT mice. After viral challenge, the viral titer and the pathological damage in lungs of MIKO mice were higher than those in WT mice despite vaccination. Interestingly, the proportions of proinflammatory immune cells including M1 macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in unvaccinated WT mice. This suggests that nonspecific activation of immune cells may paradoxically impair the response to the vaccine. In addition, although the proportions of T follicular helper (Tfh) cells and GL-7⁺ germinal center (GC) B cells were higher in MIKO mice than in WT mice, the population of CD138⁺B220⁺ antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of the low influenza-specific antibody titer in MIKO mice. Taken together, these results suggest that macrophage-derived IGF-1 might play an important role in the vaccine-triggered immune response by regulating immune cell homeostasis.



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Influenza vaccination rates in children decline when the live attenuated influenza vaccine is not recommended

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Benjamin Fogel, Steven Hicks
BackgroundIn 2016 the Centers for Disease Control and Prevention (CDC) recommended against using the live attenuated influenza vaccine (LAIV) for the 2016–2017 influenza season. This recommendation is potentially important for vaccination rates because perceived effectiveness and ease of administration are among the primary determinants of families decisions to vaccinate their children. This investigation sought to determine whether rates of pediatric influenza vaccination changed in a season when the LAIV was not recommended.MethodsThis study used cohort and cross sectional data from an academic primary care pediatric center in central Pennsylvania that serves approximately 12,500 patients. Early season (prior to November 1) and end-of-season (prior to March 1) vaccination rates in the 2015–16 and 2016–17 influenza seasons were recorded for individuals 2–17years old. Repeat vaccination rates (percentage of children receiving influenza vaccination in one season who were also vaccinated in the next season) were recorded for the 2015–16 into 2016–17 seasons. A logistic regression model adjusting for race, ethnicity, age, insurance type and type of vaccination received was employed to identify predictors of repeat vaccination.ResultsIn the absence of LAIV (2016–17) early vaccination rates were significantly higher (24.7% vs 22.8%, p=0.004), but end-of-season rates were lower (50.4% vs 52.0%, p=0.03) than when LAIV was offered (2015–16). After adjusting for covariates, those who had received IIV in the 2015–16 season had higher odds (OR 1.32, 95% CI, 1.15–1.52) of getting a repeat vaccination in the 2016–17 season, compared with those who had received LAIV in the 2015–16 season.ConclusionsEnd-of-season vaccination rates were lower in 2016–17 when LAIV was not recommended, particularly among children who received LAIV in the preceding year. Unavailability of LAIV in the 2016–17 season may have impacted influenza vaccination convenience and perceived effectiveness, two factors which could influence vaccine uptake in pediatric populations.

Graphical abstract

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Summary of workshop “global burden of diarrheal diseases among children in developing countries: Incidence, etiology, and insights from new molecular diagnostic techniques”

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Karen L. Kotloff, James A. Platts-Mills, Dilruba Nasrin, Anna Roose, William C. Blackwelder, Myron M. Levine
The Global Enteric Multicenter Study (GEMS) demonstrated that Shigella and enterotoxigenic Escherichia coli (ETEC) producing heat stable toxin (ST) (either alone or in combination with heat labile toxin) are among the most important pathogens associated with moderate-to-severe diarrhea (MSD) in children younger than 5years of age living in developing countries. To inform the design of vaccines and other interventions, we reviewed published data and new results from GEMS characterizing the burden of Shigella and ST-ETEC infections. Clinical parameters were assessed to examine the value of various case definitions as indicators of MSD associated with Shigella and ST-ETEC for use in clinical trials. We discussed advantages and disadvantages of culture-based and culture-independent molecular diagnostics for detecting clinically and epidemiologically relevant disease. Shigella serotyping data from GEMS were examined to identify desirable components of Shigella and ETEC vaccines likely to confer broad protection. These findings can inform the development and implementation of vaccines to prevent these important infections among infants and children in developing countries.



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WHO position paper, Meningococcal A conjugate vaccine: Updated guidance, February 2015

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): World Health Organization
This article presents the World Health Organization's (WHO) updated recommendations on the use of meningococcal vaccines excerpted from the WHO position paper on Meningococcal A conjugate vaccine: updated guidance, February 2015, published in the Weekly Epidemiological Record [1].A position paper on meningococcal vaccines was published in 2011 and its recommendations remain valid [2]. This update adds to the previous recommendations specifically concerning routine immunization of infants and young children in the African meningitis belt with meningococcal A conjugate vaccine.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of the Meningococcal A conjugate vaccine were discussed by SAGE in October 2014; evidence presented at these meetings can be accessed at: http://ift.tt/2u7r0k0.



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