This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larg...
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Παρασκευή 24 Νοεμβρίου 2017
Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique
A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial
Source:European Journal of Cancer, Volume 88
Author(s): Gilberto de Castro Junior, José Getúlio Segalla, Sérgio Jobim de Azevedo, Carlos José Andrade, Daniel Grabarz, Bruno de Araújo Lima França, Auro Del Giglio, Nicolas Silva Lazaretti, Maria Nunes Álvares, José Luiz Pedrini, Celio Kussumoto, João Nunes de Matos Neto, Nora Manoukian Forones, Hezio Jadir Fernandes Júnior, Giuliano Borges, Gustavo Girotto, Ismael Dale Cotrim Guerreiro da Silva, Fauze Maluf-Filho, Nils Gunnar Skare
PurposeChemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR).Patients and methodsUntreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated.ResultsWe enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44–1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm.ConclusionCombined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL.Clinical trialsIdentification number: EF024-201; Trial registry: NCT01249352.
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Farewell to monomodality treatment in patients with WHO lower grade glioma?
Source:European Journal of Cancer
Author(s): Emilie Le Rhun, Thierry Gorlia
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Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Kavit Amin, Alexandra L. Ball, Chandanpreet Chhina, Rebecca J. Edge, John P. Stone, William R. Critchley, Jason K. Wong, James E. Fildes
BackgroundPassenger leukocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia.MethodsBilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice. Each limb from the same pig underwent a post-preservation intravascular flush with isotonic solution at either 2 or 6hrs. Venous effluent underwent flow cytometry to phenotype leukocyte populations, with additional quantification of cytokines and cell-free DNA.ResultsWe identified large populations of viable leukocytes in the flush effluent (8.65x108 ±3.10x108 cells at 2hrs and 1.02x109 ±2.63x108 at 6hrs). This comprised T cells, B cells, NK cells and monocytes. Post-preservation flush yielded significant concentrations of pro-inflammatory cytokines including IL-6, IL-18, GM-CSF, IL-1β, IL1α and CXCL-8 and mitochondrial DNA. The regulatory cytokine, IL-10 was undetectable.ConclusionsThis study supports the finding that a post-preservation flush removes leukocytes and inflammatory components that are responsible for direct presentation. This study also gives an indication of how ischaemia impacts on the inflammatory burden transferred to the recipient upon reperfusion.
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Experimental assessment of the Advanced Collapsed-cone Engine for scalp brachytherapy treatments
Source:Brachytherapy
Author(s): Brie Cawston-Grant, Hali Morrison, Ron S. Sloboda, Geetha Menon
PurposeTo experimentally assess the performance of the Advanced Collapsed-cone Engine (ACE) for 192Ir high-dose-rate brachytherapy treatment planning of nonmelanoma skin cancers of the scalp.Methods and MaterialsA layered slab phantom was designed to model the head (skin, skull, and brain) and surface treatment mold using tissue equivalent materials. Six variations of the phantom were created by varying skin thickness, skull thickness, and size of air gap between the mold and skin. Treatment planning was initially performed using the Task Group 43 (TG-43) formalism with CT images of each phantom variation. Doses were recalculated using standard and high accuracy modes of ACE. The plans were delivered to Gafchromic EBT3 film placed between different layers of the phantom.ResultsDoses calculated by TG-43 and ACE and those measured by film agreed with each other at most locations within the phantoms. For a given phantom variation, average TG-43– and ACE-calculated doses were similar, with a maximum difference of (3 ± 12)% (k = 2). Compared to the film measurements, TG-43 and ACE overestimated the film-measured dose by (13 ± 12)% (k = 2) for one phantom variation below the skull layer.ConclusionsTG-43– and ACE-calculated and film-measured doses were found to agree above the skull layer of the phantom, which is where the tumor would be located in a clinical case. ACE appears to underestimate the attenuation through bone relative to that measured by film; however, the dose to bone is below tolerance levels for this treatment.
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Dosimetric impact of inter-observer catheter reconstruction variability in ultrasound-based high-dose-rate prostate brachytherapy
Source:Brachytherapy
Author(s): Alexandru Nicolae, Jure Murgic, Ivan Kruljac, Lior Dubnitzky, Laura D'Alimonte, Lin Lu, Aaron Cumal, Niki Law, Gerard Morton, Andrew Loblaw, Hans T. Chung, Ananth Ravi
PurposeTo investigate the dosimetric impact of interobserver catheter reconstruction variability in transrectal ultrasound–guided prostate high-dose-rate (HDR) brachytherapy.Methods and MaterialsTwenty consecutive patients with intermediate- or high-risk prostate cancer were treated with a single, 15-Gy HDR brachytherapy boost as part of this study. The treated plan was used as the study reference plan (PR). Three expert treatment planners (observers) manually reconstructed the catheter paths on the static three-dimensional transrectal ultrasound images, and new plans were generated from the updated positions (POBS); subsequently, the dwell time and positions from the POBS plans were superimposed on the PR catheter paths to evaluate the dosimetric effect of the interobserver variations (PEVAL). Plans from each group were stratified by observer and by number of catheters (12 or 16) and then compared using a one-way Kruskal–Wallis H test with post hoc Mann–Whitney U tests reserved for significant variations (α = 0.05).ResultsGreater than 98.9% of catheter reconstruction variations were <3 mm. When stratified by observer, there was a significant decrease (p << 0.05) in planning target volume (PTV) V100% and increases in the urethral Dmax between the POBS plans propagated to the PR catheter paths and dosimetry evaluated and PR plans only. Stratification of plans by catheter number showed nonclinically significant decreases in PTV V100%, and D90% and increases in urethral Dmax for the 12-catheter plans.ConclusionsLimiting interobserver variability, and its effects on prostate HDR brachytherapy plan quality, is critical to achieving good dosimetric outcomes; small variations in catheter reconstruction may translate to inadequate PTV coverage, excessive urethral dose, or both.
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Wound healing of cutaneous substance losses based on infectious, inflammatory and traumatic skin disorders: The experience of a center
Source:Annales de Chirurgie Plastique Esthétique
Author(s): K. Khoshim, B. Hersant, C. Hotz, M. SidAhmed-Mezi, J.P. Meningaud
IntroductionThere is no reference available concerning the standard healing time based on dermatological diseases responsible for cutaneous substance losses. The aim of our study was to assess the healing time after surgical debridement of necrotizing fasciitis (NF), hidradenitis suppurativa (HS) and skin necrosis due to trauma (SNT) based on multiples existing co-morbidities among these patients to provide surgeons with accurate scientific data in order to inform and educate patients and nurses who are practicing care under the supervision of the surgeon.Materials and methodsThis was a retrospective study. The primary endpoint was the time for complete wound healing, which was calculated from the time of the last surgical procedure to the complete wound healing corresponding to the time of complete reepithelialization, when daily dressings were no longer needed.ResultA total of 107 patients were included. The mean time for complete wound healing was 64.94±31.55 days in patients with NF, 45.70±21.40 days in patients with SNT and 75.02±26.41 days in patients with HS (SNT versus NF, P=0.004** and SNT versus HS, P<0.0001**).ConclusionThe mean time for complete wound healing was 64.94 days in patients with NF, 45.70 days in patients with SNT, 75.02 days in patients with HS. This study can be considered as a referential based on the experience of a reference centre for these 3 pathologies (NF, HS, and SNT) whose aim is to inform plastic surgeons in order to anticipate the management or educate the patient.
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Diagnostic accuracy of coronary opacification derived from coronary computed tomography angiography to detect ischemia: first validation versus single-photon emission computed tomography
Abstract
Background
Estimation of functional relevance of a coronary stenosis by fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) has recently provided encouraging results. Due to its limited availability, the corrected contrast opacification (CCO) decrease and the transluminal attenuation gradient (TAG) were suggested as less complex alternatives. The aim of the present study was to assess the accuracy of CCO decrease and TAG to predict ischemia as assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).
Results
This retrospective study included 72 patients who underwent hybrid CCTA/SPECT MPI with at least one coronary artery stenosis. Of 127 vessels with a coronary stenosis in CCTA, 38 (30%) were causing ischemia in its subtending myocardium. The area under the curve (AUC) for CCO decrease to predict ischemia was 0.707 with sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 74, 64, 85, 47, and 67%, respectively. For TAG, the AUC was 0.469.
Conclusions
CCTA-derived CCO decrease but not TAG predicts ischemia in SPECT MPI. The negative predictive value of CCO decrease of 85% may confer clinical implications in the diagnostic work-up of patients with a coronary stenosis.
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Evaluation of the novel TSPO radiotracer [ 18 F] VUIIS1008 in a preclinical model of cerebral ischemia in rats
Abstract
Background
In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [18F] VUIIS1008 have shown promising properties to visualize and quantify the in vivo expression of TSPO.
Methods
Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[18F] fluoroethoxy) phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([18F] VUIIS1008), and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a] yrimidin-3-yl)-acetamide ([18F] DPA-714) were carried out before and at days 1, 3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion (MCAO) in rats.
Results
MRI images showed the extension and evolution of the brain infarction after ischemic stroke in rats. PET imaging with [18F] VUIIS1008 and [18F] DPA714 showed a progressive increase in the ischemic brain hemisphere during the first week, peaking at day 7 and followed by a decline from days 14 to 28 after cerebral ischemia. [18F] DPA714 uptake showed a mild uptake increase compared to [18F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [18F] VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714. Finally, immunohistochemistry confirmed a high expression of TSPO in microglial cells at day 7 after the MCAO in rats.
Conclusions
Altogether, these results suggest that [18F] VUIIS1008 could become a valuable tool for the diagnosis and treatment evaluation of neuroinflammation following ischemic stroke.
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Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma
Abstract
Background
Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before.
Case presentation
Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later.
Conclusions
We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.
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Comparison between anterior segmental osteotomy versus conventional orthodontic treatment in root resorption: a radiographic study using cone-beam computed tomography
Abstract
Background
Patients who received orthodontic treatment are likely to have apical root shortening. It appears that external apical root resorption results from a combination of patient-related risk factors such as genetic influences, systemic factors, and orthodontic treatment-related factors. Regarding the fact that the anterior segmental osteotomy (ASO) has been known for its possibility of complementing external apical root resorption and of buffering periodontal problems, it has been the preferred treatment. However, the studies on the efficacy of ASO in preserving the root are not sufficient. In this study, we compared the amount of root resorption between the patients who only received orthodontic treatment and the patients who received orthodontic treatment with ASO.
Methods
This study included 28 patients (the number of incisor = 198) who received orthodontic treatment with or without ASO. We categorize them into groups A and B by the type of orthodontic treatment (group A: conventional orthodontic treatment; group B: orthodontic treatment with ASO). Cone-beam computed tomographic and cephalometric evaluations were retrospectively performed on the radiographs taken for the diagnosis of the treatment before treatment and at the end of active treatment.
Results
In group B, root resorption itself and its rate both turned out to have significantly lower than those in group A. Also, the change of incisal angle is significantly smaller in group B than in group A. On the other hand, in group A, the change of incisal angle was positively correlated with the change of AP (anteroposterior) position. In group B, the change of incisal angle was negatively correlated with the duration of the orthodontic treatment. In group B, amount of root resorption (mm) was positively correlated with the duration of the orthodontic treatment.
Conclusions
The results show lesser root resorption and shorter treatment duration with ASO than with conventional orthodontic treatment. Therefore, if the indications are accurately determined, ASO can be an effective treatment option when the amount of root resorption is expected to be high, especially in late adults.
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Treatment of dental implant displacement into the maxillary sinus
Abstract
Background
Displacement of dental implants into the maxillary sinus is rare, but it primarily occurs in patients with severe pneumatization of the maxillary sinus and/or deficiency of the alveolar process. Some complications such as the infection of the paranasal sinuses and formation of the oroantral fistula can be followed by the displacement of a dental implant. Therefore, the displaced implant has to be removed immediately with surgical intervention show and another plan for rehabilitation should be considered.
Main body
The conventional procedure for the removal of a displaced implant from the maxillary sinus involves sinus bone grafting and new implant placement performed in two or more steps with a significant time gap in between. Simplification of these surgical procedures can decrease the treatment duration and patient discomfort.
Conclusions
In this review, we discuss the anatomical characteristics of the maxillary sinus and the complications associated with implant displacement into the sinus.
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Infectious Complications following Breast Reconstruction Using Tissue Expanders in Patients with Atopic Dermatitis
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Instructions for Contributors
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PRDM14 directly interacts with heat shock proteins HSP90α and GRP78
Abstract
PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 needs to be clarified. Here, we identified the proteins interacting with PRDM14 in triple-negative breast cancer cells (TNBCs), which do not express the three most common types of receptors (estrogen receptors, progesterone receptors, and HER2). We obtained thirteen candidates that were pulled down with PRDM14 in TNBC HCC1937 and identified them by mass spectrometry. Two candidates - glucose-regulated protein 78 (GRP78) and heat shock protein 90-α (HSP90α) – were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance (SPR) analysis using GST-PRDM14 revealed that these two proteins directly interacted with PRDM14 and that the interactions required the C-terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem-like CD24-CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggested HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.
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Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010)
Abstract
This study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5,192 children with cancer (age 0-14 years) from six prefectural cancer registries in Japan and 21,295 children diagnosed in England during 1993-2010. Differences in incidence rates between the two countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumours, and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumours, hepatic tumours, neuroblastoma, and acute myeloid leukaemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumours, soft tissue sarcomas, malignant bone tumours, and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening programme for neuroblastoma. The large improvement in survival from CML coincided with the introduction of effective therapy (imatinib).
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CT Imaging of Emergent Renal Conditions
The kidneys are paired intra-abdominal organs which provide essential functions and maintain homeostasis throughout the human body. Numerous disease processes affect the kidneys and cause acute renal dysfunction or other potentially catastrophic complications. These conditions can be broadly categorized into obstructive, infectious, hemorrhagic, traumatic and vascular diseases. Imaging plays a vital role in the work-up and diagnosis of acute and emergent renal conditions. Evaluation of emergent renal conditions with a focus on CT imaging are discussed.
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Association Between Pepsin in the Saliva and the Subjective Symptoms in Patients With Laryngopharyngeal Reflux
Our study was designed to further evaluate the relationships between the saliva pepsin level and the symptoms and quality of life of patients with laryngopharyngeal reflux (LPR).
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Pin-up Glottoplasty: Feasibility Study of a Novel Approach Medializing or Lateralizing Immobile Vocal Folds
Principles in medializing and lateralizing vocal folds have not changed a lot within the last decades (Isshiki et al, 1974; Bruenings, 1911). We present a feasibility study for a completely new approach to perform medialization and lateralization of immobile vocal folds.The method was tested on 20 human larynges by inserting a 21G needle into the vocal fold, medializing (or, in other cases, lateralizing) the vocal cord and fixing the needle at the cricoid cartilage posteriorly. The anterior and posterior fixation points of the needle allow for a stable positioning of the needle, which we consider necessary in both cases of medialization or lateralization.
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Dimensions of hard and soft tissue around adjacent, compared with single-tooth, zirconia implants
Preservation or regeneration of the papilla has always been a challenge around consecutive implants or with implants next to teeth, and many studies have evaluated the papilla's behaviour and patterns based on surgical technique and prosthetic design, though evidence about its behaviour around zirconia implants is scarce. The aim of this study was to evaluate papilla behaviour between implants and teeth (tooth-implant group) and between consecutive implants (implant–implant group). Ninety patients with 122 zirconia implants (Straumann® PURE Ceramic Implant) were examined at the one-year follow up.
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Recurrence of oral mucocoeles in adolescents after excision
Although mucocoeles can occur at any age, children and adolescents are most commonly affected, and excision is the most common treatment.1
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Upregulation of angiogenesis in oral lichen planus
Abstract
Objectives
Since angiogenesis is fundamental to the pathogenesis of many chronic inflammatory disorders this study investigated the expression of various vascular markers in oral lichen planus and non-specific oral mucosal inflammatory tissues.
Methods
Archival specimens of oral lichen planus (n=15) and inflamed tissues (n=13) were stained using immunohistochemistry with antibodies to CD34, vascular endothelial growth factor, vascular endothelial growth factor receptor and vasohibin. Nine representative sites at the epithelial-connective tissue junction and through the fibrous connective tissue were selected and automated analysis techniques were used to determine the extent of positivity expressed as the percentage of positive cells. Significance was denoted when p<0.05.
Results
The expression of pro-angiogenic factors was higher in lichen planus samples compared with inflamed controls. A higher level of CD34 was observed in the deeper parts of the connective tissue of OLP (p=0.04), whereas VEGF and VEGFR2 expression was higher all through the tissues (respectively p<0.02 and p<0.01). The expression of the anti-angiogenic VASH1 was higher in inflamed tissue compared with lichen planus in all sites evaluated (p<0.01).
Conclusions
The findings indicate that angiogenic factors are differentially expressed in oral lichen planus compared with inflamed controls, with increased expression of pro-angiogenic factors and decreased anti-angiogenic expression.
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Somatosensory Evoked Potentials and Central Motor Conduction Times in Children with Dystonia and their correlation with outcomes from Deep Brain Stimulation of the Globus pallidus internus
The benefits of Deep Brain Stimulation (DBS) of the Globus Pallidus internus (GPi) for isolated idiopathic or genetic (formerly termed primary) dystonia are now well recognised in both adults and children, with improvements of 52-88% being seen in the Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-m)(Coubes et al., 2004; Vidailhet et al., 2005; Zorzi et al., 2005, Alterman et al., 2007). However, isolated dystonia, in which the dystonic movements are the only feature of the neurological disease and structural neuroimaging is normal, is rare, especially in childhood (Roubertie et al., 2002).
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Clinical effects of submucosal middle turbinectomy for eosinophilic chronic rhinosinusitis
The preservation or resection of the middle turbinate (MT) during endoscopic sinus surgery (ESS) currently remains a matter of debate. The present study aimed to investigate the effects of submucosal middle turbinectomy (SMT) in ESS for eosinophilic chronic rhinosinusitis (ECRS).
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The association between atopic dermatitis and hand eczema: a systematic review and meta-analysis
Abstract
Atopic dermatitis (AD) and hand eczema (HE) are common chronic and relapsing inflammatory skin conditions that often co-occur. While several studies have addressed their relationship, the exact association estimate is unknown. We systematically reviewed published literature on the association between AD and HE in PubMed, Embase, and Web of Science using the following search terms; (atopic dermatitis OR atopic eczema) AND (hand dermatitis OR hand eczema). Meta-analyses were then performed to examine the association between AD and the point-, one-year- and lifetime prevalence of HE, respectively. We identified 35 relevant studies, of which 26 were included in the meta-analyses. AD was associated with an increased prevalence of HE with regards to point- (odds ratio (OR) 2.35; 95% CI: 1.47-3.76), one-year- (OR 4.29; 95% CI: 3.13-5.88), and lifetime prevalence (OR 4.06; 95% CI: 2.72-6.06). Furthermore, positive associations between AD and occupational HE were identified when assessing the one-year- 4.31 (95% CI: 2.08-8.91) and lifetime prevalence (OR 2.81; 95% CI: 2.08-3.79). Similar positive associations were found in the general population studies, i.e. OR 4.19 (95% CI: 3.46-5.08) and OR 5.69 (95% CI: 4.41-7.36). Important study limitations include the wide use of questionnaire studies, and lack of prospective studies as well as poor clinical phenotype descriptions. In conclusion, our systematic review and meta-analysis showed that patients with AD had a strongly increased prevalence of HE. Clinicians should continue to guide patients with AD away from occupations with high risk of HE.
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Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation
Passenger leukocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia.
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Sensitivity and specificity of Frontal Assessment Battery in newly diagnosed and untreated Obstructive Sleep Apnea patients
Executive dysfunction (ED) is often observed in subjects diagnosed with obstructive sleep apnea (OSA), but their assessment requires facilities that are not always available. We aim to evaluate the extent to which Frontal Assessment Battery (FAB) discriminates ED in newly diagnosed, untreated and without comorbidities OSA patients.
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Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: An IRLSSG task force report
Brain iron deficiency has been implicated in the pathophysiology of RLS, and current RLS treatment guidelines recommend iron treatment when peripheral iron levels are low. In order to assess the evidence on the oral and intravenous (IV) iron treatment of RLS and periodic limb movement disorder (PLMD) in adults and children, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force to review these studies and provide an evidence-based and consensus guidelines for the iron treatment of RLS in adults, and RLS and PLMD in children.
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Limb girdle muscular dystrophy due to mutations in POMT2
Background
Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have been reported so far.
ClinicalTrials.gov ID: NCT02759302
MethodsWe report 12 new cases of LGMD2N, aged 18–63 years. Muscle involvement was assessed by MRI, muscle strength testing and muscle biopsy analysis. Other clinical features were also recorded.
ResultsPresenting symptoms were difficulties in walking, pain during exercise, delayed motor milestones and learning disabilities at school. All had some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10 patients, showing ventricular enlargement in one, periventricular hyperintensities in another and frontal atrophy of the left hemisphere in a third patient. Most affected muscle groups were hip and knee flexors and extensors on strength testing. On MRI, most affected muscles were hamstrings followed by paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles with known mutations, whereas 11 novel mutations accounted for the remaining 13 alleles.
ConclusionWe describe the first cohort of patients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment. Primary muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI, which correlated well with reduced muscle strength in hip and knee flexors and extensors. The study expands the mutational spectrum for LGMD2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N.
Clinical trial registrationNCT02759302.
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Compulsive sexual behaviour in Parkinsons disease is associated with higher doses of levodopa
Introduction
Previous research estimates the lifetime prevalence of compulsive sexual behaviour (CSB) in individuals with Parkinson's disease (PD) to be 2.7%. CSB has also been associated with male gender and earlier onset of PD.1 Although both dopamine agonists (DAs) and, to a lesser extent, levodopa have been associated with impulsive compulsive behaviours (ICBs),2 it is still unclear whether higher levodopa doses are a risk factor for the development of CSB in patients with PD.
MethodsPatients with ICBs were identified from a database of individuals with PD and ICBs who were seen at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK, and who had participated in three previous research projects over an 8-year period (from 2008 to 2016). All the ICB cases were recruited to research studies from PD clinics at the National Hospital and selected due to the reporting of ICBs. All cases underwent a...
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Oral corticosteroid dosing regimen and long-term prognosis in generalised myasthenia gravis: a multicentre cross-sectional study in Japan
Objective
We examined the correlation between the dosing regimen of oral prednisolone (PSL) and the achievement of minimal manifestation status or better on PSL ≤5 mg/day lasting >6 months (the treatment target) in patients with generalised myasthenia gravis (MG).
MethodsWe classified 590 patients with generalised MG into high-dose (n=237), intermediate-dose (n=187) and low-dose (n=166) groups based on the oral PSL dosing regimen, and compared the clinical characteristics, previous treatments other than PSL and prognosis between three groups. The effect of oral PSL dosing regimen on the achievement of the treatment target was followed for 3 years of treatment.
ResultsTo achieve the treatment target, ORs for low-dose versus high-dose regimen were 10.4 (P<0.0001) after 1 year of treatment, 2.75 (P=0.007) after 2 years and 1.86 (P=0.15) after 3 years; and those for low-dose versus intermediate-dose regimen were 13.4 (P<0.0001) after 1 year, 3.99 (P=0.0003) after 2 years and 4.92 (P=0.0004) after 3 years. Early combined use of fast-acting treatment (OR: 2.19 after 2 years, P=0.02; OR: 2.11 after 3 years, P=0.04) or calcineurin inhibitors (OR: 2.09 after 2 years, P=0.03; OR: 2.36 after 3 years, P=0.02) was associated positively with achievement of treatment target.
ConclusionA low-dose PSL regimen with early combination of other treatment options may ensure earlier achievement of the treatment target in generalised MG.
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Clinical course of MOG antibody-associated recurrent demyelinating diseases
Antibodies to the myelin oligodendrocyte glycoprotein are associated with a relapsing disease course, with optic neuritis being the most frequent clinical presentation at onset and relapse
Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are present in patients with acute disseminated encephalomyelitis (ADEM), aquaporin-4 antibody-negative neuromyelitis optica spectrum disorders (NMOSD), isolated optic neuritis (ON), transverse myelitis, encephalomyelitis or brainstem encephalitis, but only rarely in people with multiple sclerosis (MS). Initial studies indicated that MOG antibodies are associated with a monophasic and more benign disease course, whereas recent findings challenged this assumption. These studies revealed that MOG antibodies are also found in patients with a recurrent non-MS disease course, particularly in adolescents and adults.1–4 The most frequent clinical presentation at relapse is ON, and the majority of patients are finally diagnosed with NMOSD or related disorders such as recurrent ON.
In their JNNP manuscript, Ramanathan and colleagues
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Mediterranean fever gene mutations in patients with possible neuro-Sweet disease: a case series
Introduction
Neuro-Sweet disease (NSD) is defined as Sweet disease with central nervous system (CNS) involvement. Also known as acute febrile neutrophilic dermatosis, NSD is characterised by painful erythematous plaques and multisystem neutrophilic infiltration.1
Familial Mediterranean fever (FMF), characterised by recurrent fever and serositis, is caused by mutations of the Mediterranean fever (MEFV) gene. FMF is rarely reported in patients with Sweet's syndrome.2 In this report, we discuss three cases of possible NSD. Our findings indicate that some mutations in the MEFV gene may act as additional susceptibility factors in autoimmune inflammatory neurological diseases, including NSD.
Patients and methodsWe conducted MEFV mutation analyses on genomic DNA samples from three patients diagnosed with possible NSD between 1 April 2014 and 31 October 2016. Patients were diagnosed with NSD in accordance with previously described criteria.1 In all patients, infection, malignancy and other autoimmune diseases were clinically excluded. All patients provided...
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Acute-onset chronic inflammatory demyelinating polyneuropathy after Zika virus infection
Case description
In December 2016, a 69-year-old man with a history of hypertension, hypercholesterolaemia and knee operations developed an erythematous pruritic rash on his trunk, cold shivers and swollen hands and feet with paraesthesias and numbness while on holiday in Curacao. Eight days later he developed pain in his right leg and back, provoked by walking and stretching. This pain slowly increased over the next 5 weeks to the point that it became difficult to walk. He was admitted to the neurology ward of a regional hospital in The Netherlands, and neurological examination showed an antalgic gait, hypaesthesia of fingertips and feet and normal muscle strength and tendon reflexes. MRI of the cervical, thoracic and lumbar spine without gadolinium was normal. Eight days after admission he developed a progressive weakness of the legs starting in the right leg. Neurological examination showed a proximal and distal flaccid paraparesis with absent reflexes...
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Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1
Abstract
Background
Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project.
Methods
The ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mAb to compete with patients' IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site-directed mutagenesis and hydrogen/deuterium exchange-mass spectrometry.
Results
The 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping with the binding sites of patients' serum IgEs. Mutation of residues P59, E60 and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44-K55 and R70-F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mAbs interact with >90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross-reactivity with other allergens of the PR-10 family.
Conclusions
MAbs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1-specific quantitative ELISA adopted by the European Pharmacopoeia.
This article is protected by copyright. All rights reserved.
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Oxalate Enhances Desorption of Perfluorooctane Sulfonate from Soils and Sediments
Abstract
Perfluorooctane sulfonate (PFOS) is one of the most widespread toxic substances in water distribution systems, posing a significant risk to public health and the environment due to its toxic and non-biodegradable nature. In this study, the effect of oxalate on PFOS adsorption/desorption to/from soil and sediment samples was studied with batch experiments. Dissolved organic carbon content in soil strongly enhanced the retention of organic halogens. Oxalate increased PFOS desorption by 1.43- to 17.14-fold and significantly increased the release of dissolved organic carbon and inorganic ions in soils. The effects of root exudates were similar to those of oxalate. Addition of low molecular weight dissolved organic carbon caused partial dissolution of the soil structure (e.g., through formation of organo-mineral complexes), resulting in the release of organic carbon and metal ions and subsequently enhancing PFOS desorption. The effects of oxalate on organic halogen desorption were influenced by dissolved organic carbon content and formation of calcium oxalate.
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Low Arid1a Expression Correlates with Poor Prognosis and Promotes Cell Proliferation and Metastasis in Osteosarcoma
Abstract
AT-rich interactive domain-containing protein 1A (ARID1A) has been shown to function as a tumour suppressor in various malignancies. However, the biological role of ARID1A in osteosarcoma is not clear. The present study aimed to investigate the expression pattern, prognostic value and the biological role of ARID1A in human osteosarcoma. ARID1A expression in 53 osteosarcoma surgical specimens was examined by quantitative real-time polymerase chain reaction, and its clinical significance was analysed. The role of ARID1A in cell proliferation, apoptosis, and metastasis were examined. ARID1A mRNA expression were significantly down-regulated in osteosarcoma tumours from that in matched adjacent non-tumour tissues. ARID1A expression was significantly inversely correlated with tumour stage and distant metastasis, as well as poor overall survival in patients with osteosarcoma. Furthermore, ARID1A mRNA was down-regulated in four human osteosarcoma cell lines MG-63, U2OS, HOS and Saos-2. Restoring of ARID1A expression in MG-63 and U2OS cells significantly inhibited cell proliferation and metastasis in vitro. Collectively, our data demonstrate that ARID1A may serve as a tumour suppressor in osteosarcoma progression, and represent a valuable prognostic marker and potential therapeutic target for osteosarcoma.
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Risk of inferior alveolar nerve injury with coronectomy versus surgical extraction of mandibular third molars - A comparison of two techniques and review of the literature
Abstract
Background
The removal of mandibular third molar teeth is one of the most common oral surgical procedures. In a significant number of patients it carries a degree of associated morbidity, including damage to the inferior alveolar nerve (IAN). For this reason, practitioners desire the most up-to-date guidance on the most appropriate technique, informed by the best available evidence that will produce the lowest incidence of iatrogenic complications.
Objective
Perform a systematic review comparing the effect of coronectomy versus complete surgical extraction of mandibular third molar teeth on the risk of IAN injury and other complications in adults.
Data Sources
Studies were identified through Embase (1980-2015) and Ovid MEDLINE (1946-2015) database searches. Search terms included coronectomy, partial root removal, deliberate vital root retention, odontectomy, surgical removal, surgical extraction, complete tooth extraction, and extract*. Limits included humans, English language, and randomized controlled trials (RCTs).
Inclusion criteria
Only RCTs comparing IAN damage associated with surgical extraction of mandibular third molars versus coronectomy were included.
Results
From our database searches, we identified two unique RCTs matching the inclusion criteria. Both evaluated patients who had specific radiographic signs of intimate relationships with the IAN. Upon detailed analysis, the studies were noted to exhibit a high risk of bias in many categories, thereby rendering their results inconclusive.
Conclusion
Although evidence from two RCTs suggests that coronectomy can reduce the risk of IAN injury compared to surgical removal of high-risk mandibular third molars, the quality of evidence is insufficient to provide definitive conclusions regarding the preferred technique.
This article is protected by copyright. All rights reserved.
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Mutant huntingtin protein expression and blood-spinal cord barrier dysfunction in Huntington's disease
Abstract
Objective: The aim of the study was to assess the distribution, frequency and specific location of mutant huntingtin protein (mHTT) aggregates - the pathological hallmark of HD - within the various compartments of the spinal cord and their potential impact on the local vasculature and BSCB.
Methods: We performed a series of post-mortem immunohistochemical and immunofluorescent stainings, as well as western blot analyses, on cervical and lumbar sections of the spinal cord in patients diagnosed with HD (n=11 of all grades of disease severity) along with sex and age-matched healthy controls (n=9).
Results: We observed that mHTT was preferably expressed within the anterior horn of the grey matter, in both cervical and lumbar sections. At the cellular level, mHTT aggregates were more often encountered in the extracellular matrix but could also be observed within cell bodies, neurites as well as within the endothelium of blood vessels with an increase in the density of small blood vessels in cervical sections of HD cases. These vasculature changes were accompanied with features of BSCB leakage, as assessed by the presence of increased levels of fibrinogen in the surrounding parenchyma and enhanced leukocyte infiltration.
Interpretation: This alteration in BSCB integrity may be explained, in part, by the dysregulation we found in some of the main proteins associated with it such as the junctional adhesion molecule-1 (JAM-1) and vascular endothelial cadherin (VE-cadherin). These observations have important implications for our understanding of HD pathology and may also have significant therapeutic implications. This article is protected by copyright. All rights reserved.
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Building on NeuroNEXT: “Next Generation” Clinics to Cure Chronic Neurological Disability
Abstract
Chronic disability from neurological conditions is a looming, if not present, epidemic. The combination of an increasingly aged population, and our improved ability to keep patients alive after acute neurological injury, means that the ranks of the chronically disabled are swelling. Indeed, it is estimated that by 2050, the leading causes of motor and cognitive disability in the United States- stroke and Alzheimer's disease-, will cost the country $1.4 trillion per year1-3. If these daunting numbers do not provoke action to accelerate progress on their own, the human suffering wrought by these conditions should. This article is protected by copyright. All rights reserved.
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Clinical and genetic findings in children with CNS arteriovenous fistulas
Abstract
Objective:
To assess the spectrum of genetic anomalies in a cohort of children presenting at least one cerebral or spinal pial arteriovenous fistula (AVF), and to describe their clinical characteristics.
Methods:
From 1988 to 2016, all consecutive patients with at least one cerebral or spinal pial AVF were screened for genetic disease. All patients under the age of 18 years were included. Symptoms associated with AVF were recorded: heart failure, neurologic deficit/seizure, hemorrhage. The outcome was assessed using the mRS and school performance in children with cerebral AVF and the ASIA impairment scale in children with spinal AVF.
Results:
Forty-three children were included. Twenty-five children were male and 18 were female. A germline mutation was identified in 23 probands (53.5%±14.9%): 8 in ENG (34.8%±14.2%), 1 in ACVRL1 (4.3%±6%) leading to a diagnosis of HHT and 14 in RASA1 (60.9%±14.4%) leading to a diagnosis of CM-AVM1. No EphB4 gene mutation was identified. HHT patients presented a significantly lower rate of heart failure at diagnosis (p =0.047). A trend towards an increased bleeding rate at presentation was observed in HHT (p=0.069) and an increased rate of giant venous pouch in children in whom no mutation was identified (p=0.097). Finally, an association with RASA1 mutation was observed in children with associated skin capillary hemangioma (p<0001).
Interpretation:
These results highlight the importance of genetic testing in this setting in view of the high frequency of gene mutations in pediatric cerebrospinal AVFs, and show the predominance of RASA1 over HHT mutations. This article is protected by copyright. All rights reserved.
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Increasing motor neuron excitability to treat weakness in sepsis
Abstract
Objective: Weakness induced by critical illness (intensive care unit acquired weakness) is a major cause of disability in patients and is currently untreatable. We recently identified a defect in repetitive firing of lower motor neurons as a novel contributor to intensive care unit acquired weakness. In order to develop therapy for intensive care unit acquired weakness, it was necessary to determine the mechanism underlying the defect in repetitive firing.
Methods: Both computer simulation and in vivo dynamic voltage clamp of spinal motor neurons in septic rats were employed to explore potential mechanisms underlying defective repetitive firing.
Results: Our results suggested alteration in subthreshold voltage-activated currents might be the mechanism underlying defective repetitive firing. It has been shown previously that pharmacologic activation of serotonin receptors on motor neurons increases motor neuron excitability, in part by enhancing subthreshold voltage-activated inward currents. Administration of a food and drug administration approved serotonin agonist (lorcaserin) to septic rats greatly improved repetitive firing and motor unit force generation.
Interpretation: Our findings suggest activation of serotonin receptors with lorcaserin may provide the first ever therapy for intensive care unit acquired weakness in patients. This article is protected by copyright. All rights reserved.
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Targeting Hypersensitive Corticostriatal Terminals in Restless Legs Syndrome
ABSTRACT
Objective: The first aim was to demonstrate a previously hypothesized increased sensitivity of corticostriatal glutamatergic terminals in the rodent with brain iron deficiency (BID), a pathogenetic model of Restless Legs Syndrome (RLS). The second aim was to determine if these putative hypersensitive terminals could constitute a significant target for drugs effective in RLS, including dopamine agonists (pramipexole and ropinirole) and α2δ ligands (gabapentin).
Methods: A recently introduced in vivo optogenetic-microdialysis approach was used, which allows the measurement of the extracellular concentration of glutamate upon local light-induced stimulation of corticostriatal glutamatergic terminals. The method also allows to analyze the effect of local perfusion of compounds within the same area being sampled for glutamate.
Results: BID rats showed hypersensitivity of corticostriatal glutamatergic terminals (lower frequency of optogenetic stimulation to induce glutamate release). Both hypersensitive and control glutamatergic terminals were significant targets for locally perfused pramipexole, ropinirole and gabapentin, which significantly counteracted optogenetically-induced glutamate release. The use of selective antagonists demonstrated the involvement of dopamine D4 and D2 receptor subtypes on the effects of pramipexole.
Interpretation: Hypersensitivity of corticostriatal glutamatergic terminals can constitute a main pathogenetic mechanism of RLS symptoms. Selective D4 receptor agonists, by specifically targeting these terminals, should provide a new efficient treatment with less secondary effects. This article is protected by copyright. All rights reserved.
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Matching-Adjusted Indirect Comparison of Efficacy in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Ixekizumab Versus Secukinumab
Abstract
Background
Head-to-head randomised studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available.
Objective
Assess efficacy and quality of life with ixekizumab vs. secukinumab treatment using matching-adjusted indirect comparisons.
Methods
Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved doses of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) and two modified versions of the Signorovitch method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis.
Results
In meta-analysis of studies with active comparators, PASI 90 response rates were 12.7% (95% CI: 5.5%-19.8%; p=0.0005), 10.0% (2.1%-18.0%; p=0.01) and 11.2% (3.2%-19.1%; p=0.006) higher and PASI 100 response rates 11.7% (5.9%-17.5%; p<0.001), 12.7% (6.0%-19.4%; p<0.001) and 13.1% (6.3%-19.9%; p<0.001) higher for ixekizumab compared to secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and in favor of ixekizumab using BU method. Week 12 DLQI 0/1 response rates did not differ significantly.
Conclusion
Ixekizumab had higher PASI 90 and PASI 100 responses at Week 12 compared to secukinumab using adjusted indirect comparisons.
This article is protected by copyright. All rights reserved.
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Description of the sagittal alignment of the degenerative human spine
Abstract
Purpose
To present the description of sagittal alignment of the degenerative human spine and its possible evolution.
Materials and methods
This is a retrospective observational study of degenerative evolution in spinal alignment in low back pain patients. Full spine EOS® sagittal X-rays were analyzed, and pelvic and spinal parameters were measured. Spinal shapes were classified on the hypothesis that the possible sagittal shapes of degenerative spine would be divided into four categories: "classical" Roussouly types 1–4, anteverted types (PT ≤ 5), retroverted types (PT ≥ 25) and kyphotic types.
Results
A total of 331 patients (280 women and 51 men) were included. "Classic" types 1–4 represented the majority in this cohort (71.9%). Retroverted types made the second most common category with 20.8% of the cohort. Kyphosis group (lumbar and global) make only 5.8% of this cohort, while anteverted group make the lowest incidence (1.5%). Retroverted type 2 with thoracic kyphosis should be considered a separate type and made 1.5% of this cohort. Two theoretical subtypes, retroverted type 1 and type 4 were not found.
Conclusions
This is the first description of degenerative spine disease based on its shape and based on the classification of the normal variation in the sagittal alignment of the human lumbar spine described by Roussouly. Eleven types, divided into classical types, anteverted types, false shapes (retroverted) and kyphotic shapes, are described and an evolution pathway is proposed. An evaluation of surgical results in order to propose a treatment algorithm based on this classification should follow.
Level of evidence
Level IV cross sectional observational study.
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AHNS Series: Do you know your guidelines? Principles of treatment for locally advanced or unresectable head and neck squamous cell carcinoma
Abstract
This article is a continuation of the "Do You Know Your Guidelines" series, initiated by the Education committee of the American Head and Neck Society. Treatment guidelines for advanced head and neck squamous cell carcinoma are reviewed here, including the critical roles of radiotherapy, chemotherapy, and the recent application of immunotherapy agents. We will be limiting this discussion to include cancers of the oral cavity, oropharynx, hypopharynx, and larynx. It should be noted that much of the article pertains to human papillomavirus (HPV)-negative oropharyngeal cancer where applicable, as HPV-positive oropharyngeal squamous cell carcinoma carries a different natural history, different prognosis, and now different staging criteria. Additionally, the article will not include information on nasopharyngeal or sinus cancers, as these latter topics are covered in separate "Do you know your guidelines?" installments and these diagnoses carry somewhat different approaches to diagnosis and management that diverge from the focus of this article.
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Concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat allergy
Abstract
Background
Buckwheat (Fagopyrum esculentum) has become increasingly popular as a healthy food in Europe. However, for sensitized individuals, consumption can cause anaphylactic reactions. The aim of this study was to identify individual well-characterized buckwheat allergens for component resolved diagnosis.
Methods
Patients were selected by positive skin prick test to buckwheat and divided into two groups: (1) sensitized to buckwheat without clinical symptoms and (2) buckwheat allergy. Buckwheat proteins were extracted from raw buckwheat seeds, purified applying a combination of protein precipitation and chromatographic methods and analyzed by IgE immunoblotting and ELISA.
Results
Buckwheat-allergic patients had a significantly larger median skin prick test wheal diameter for buckwheat than the sensitized group and the positive control. Also, IgE-immunoblotting clearly showed a distinct pattern in sera from allergic patients when compared to sensitized individuals. Several IgE-reactive proteins were purified from crude buckwheat extract, namely legumin (Fag e 1 plus its large subunit), Fag e 2 (2S albumin), and newly identified Fag e 5 (vicilin-like) as well as hevein-like antimicrobial peptides, designated Fag e 4. All four allergens showed superior diagnostic precision compared to extract-based ImmunoCAP with high sensitivity as well as high specificity.
Conclusions
Patients with clinical symptoms clearly show a distinct allergen recognition pattern. We characterized a buckwheat vicilin-like protein as a new relevant marker allergen, designated Fag e 5. Additionally, another new allergen, Fag e 4, potentially important for cross-reactivity to latex was added to the allergen panel of buckwheat. Further, our data show that the full-length legumin comprising both, large and small subunit should be applied for component resolved diagnosis. Our data indicate that concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat allergy.
This article is protected by copyright. All rights reserved.
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Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain Injury
Abstract
Objective
Neuronal exosomes purified from peripheral blood samples have been proposed as diagnostic tool in the setting of acute brain injury but never tested clinically. We hypothesized that exosome protein biomarkers would change over time following acute hypoxic brain injury and would predict response to therapy.
Methods
Synaptopodin (SYNPO), an actin-associated protein present in postsynaptic spines, was evaluated as a potential biomarker as well as: synaptophysin, neuron-specific enolase, and mitochondrial cytochrome c oxidase. A secondary analysis was performed on neonatal samples collected at 8, 10, and 14 h after the initiation of therapeutic-controlled hypothermia for acute hypoxic–ischemic encephalopathy (n = 14). Neuronal exosomes were purified from serum and protein levels were quantified using standard ELISA methods. The primary study outcomes were length of stay (LOS), discharge on seizure medication (DCMED), and composite neuroimaging score (NIS).
Results
The slope of change in neuronal exosome SYNPO between 8 and 14 h appeared to be the most promising biomarker for all three clinical study outcomes. SYNPO was highly correlated with LOS (−0.91, P < 0.001). SYNPO increased in 6/8 without DCMED and was worse or neutral in 5/5 with DCMED (P = 0.02). All four neonates with an abnormal NIS had neutral or decreasing SYNPO (P = 0.055). Other candidate biomarkers were not associated with outcomes.
Interpretation
This report provides the first clinical evidence that neural exosomes turn over rapidly enough in the peripheral circulation to be used as a "troponin-like" test following acute brain injury. Optimal sampling and biomarkers likely vary with type of brain injury.
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Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy
Abstract
Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in the degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to accumulation of partially degraded heparan sulphate within lysosomes and the extracellular matrix, giving rise to severe CNS degeneration with progressive cognitive impairment and behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy in the related disease mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the brain following bone marrow engraftment, secrete the missing enzyme and cross-correct neighbouring cells. However, little neurological correction is achieved in patients with mucopolysaccharidosis IIIB. We have therefore developed an ex vivo haematopoietic stem cell gene therapy approach in a mouse model of mucopolysaccharidosis IIIB, using a high-titre lentiviral vector and the myeloid-specific CD11b promoter, driving the expression of NAGLU (LV.NAGLU). To understand the mechanism of correction we also compared this with a poorly secreted version of NAGLU containing a C-terminal fusion to IGFII (LV.NAGLU-IGFII). Mucopolysaccharidosis IIIB haematopoietic stem cells were transduced with vector, transplanted into myeloablated mucopolysaccharidosis IIIB mice and compared at 8 months of age with mice receiving a wild-type transplant. As the disease is characterized by increased inflammation, we also tested the anti-inflammatory steroidal agent prednisolone alone, or in combination with LV.NAGLU, to understand the importance of inflammation on behaviour. NAGLU enzyme was substantially increased in the brain of LV.NAGLU and LV.NAGLU-IGFII-treated mice, with little expression in wild-type bone marrow transplanted mice. LV.NAGLU treatment led to behavioural correction, normalization of heparan sulphate and sulphation patterning, reduced inflammatory cytokine expression and correction of astrocytosis, microgliosis and lysosomal compartment size throughout the brain. The addition of prednisolone improved inflammatory aspects further. Substantial correction of lysosomal storage in neurons and astrocytes was also achieved in LV.NAGLU-IGFII-treated mice, despite limited enzyme secretion from engrafted macrophages in the brain. Interestingly both wild-type bone marrow transplant and prednisolone treatment alone corrected behaviour, despite having little effect on brain neuropathology. This was attributed to a decrease in peripheral inflammatory cytokines. Here we show significant neurological disease correction is achieved using haematopoietic stem cell gene therapy, suggesting this therapy alone or in combination with anti-inflammatories may improve neurological function in patients.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2svXy
Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?
Abstract
The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma (RCC) led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in RCC, including interpretation of currently available conflicting data and future direction of research.We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate endpoint for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A9bPf9
Meta-analysis of induction chemotherapy as selection marker for chemoradiation in the head and neck
Objective
Many trials incorporate induction chemotherapy (IC) in selecting for organ preservation in head and neck squamous cell carcinomas (HNSCC). However, few studies examine IC response in predicting for chemoradiation therapy (CRT) response. This meta-analysis aims to determine the predictive accuracy of IC for subsequent response to CRT and overall survival (OS).
Data sources
Medline, EMBASE, Cochrane register.
Methods
A systematic search identified studies from database inception to October 2016 that used IC prior to CRT as definitive treatment for advanced HNSCC. The sensitivities and specificities of IC response predicting for complete CRT response were calculated, and the results were pooled in a summary receiver operating curve. One-, 2- and 5-year OS data were extracted.
Results
Seven studies (n = 423 patients) were analyzed for response and six (n = 439) for OS. Pooled median sensitivity and specificity of IC response predicting CRT response were 0.95 (95% confidence interval [CI]: 0.72–0.98) and 0.43 (95% CI: 0.00–0.61), respectively. Patients were more likely to respond to CRT given previous response to IC (positive likelihood ratio = 1.6; 95% CI: 1.21–2.11) and less likely to respond to CRT if they failed to respond to IC (negative likelihood ratio = 0.16; 95% CI: 0.07–0.38). At 2 years, good response to IC was a statistically significant prognostic marker with a risk ratio of 1.35 (95% CI: 1.12–1.64).
Conclusion
Our data suggests that patients with poor IC response will have poorer response to CRT and should be directed to other modalities. In contrast, good IC response does not guarantee a favorable outcome to CRT; however, because these patients are likely to have better prognoses, they should be offered salvage therapies of curative intent despite treatment failure.
Level of Evidence
NA. Laryngoscope, 2017
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Cognitive impairment in epilepsy: the role of reduced network flexibility
Abstract
Objective
The dominant model of cognitive impairment in focal epilepsy has emphasised structural bases for cognitive deficits. Current theories of cognition in the healthy brain emphasise the importance of the reweighting of brain network interactions in support of task performance. Here, we explore the hypothesis that cognitive deficits in epilepsy arise through abnormalities of dynamic functional network interactions.
Method
We studied 19 healthy controls and 37 temporal lobe epilepsy (TLE) patients, using a behavioural measure of verbal fluency (the Controlled Oral Word Association Test) and an fMRI verbal fluency paradigm (Orthographic Lexical Retrieval).
Results
Behaviourally, verbal fluency was significantly impaired in TLE. Psychophysiological interaction analyses of the fMRI data, which capture state-dependent changes in network connectivity, revealed reduced task-dependent modulations of connectivity from left superior medial frontal cortex to left middle frontal gyrus in TLE patients. Individual differences in verbal fluency among TLE cases was correlated with task-dependent changes in connectivity from left posterior cingulate to left superior medial frontal cortex, and from left superior medial frontal cortex to a range of right predominant brain areas.
Interpretation
These data reveal that the typical pattern of task-driven shifts in network connectivity is not observed in TLE. Our observations go beyond simple structure-function associations and suggest that failure of network flexibility can be an important contributor to cognitive impairment in epilepsy.
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Infectious risk stratification in multiple sclerosis patients receiving immunotherapy
Abstract
The increasing number of potent treatments for multiple sclerosis warrants screening for infections. To investigate the prevalence of infections in two independent German patient cohorts with multiple sclerosis/neuromyelitis optica spectrum disorders (NMOSD), we performed a retrospective chart review study of multiple sclerosis/NMOSD patients who underwent testing for infections between 2014 and 2016. We show that 6 out of 80 tested patients (Düsseldorf cohort) and 2 out of 97 tested patients (Münster cohort) had a latent tuberculosis infection; total 3.95%, 95% CI: 2–8%. Our findings suggest that latent tuberculosis infection is frequent (>1%). Screening should be performed before embarking on immunomodulatory therapies to allow treatment and mitigation of the risk of a reactivation.
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Anaphylactic shock following castor bean contact: a case report
The castor bean plant, Ricinus communis, is known to have allergenic and toxic properties. Castor bean allergy has been described mainly as an occupational inhalation allergy in laboratory workers, in persons wor...
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Potential treatment for vocal fold scar with pirfenidone
Objectives/Hypothesis
Pirfenidone (PFD) is a strong antifibrotic agent that has been clinically approved in Japan for idiopathic pulmonary fibrosis. We examined the antifibrotic effects of PFD on fibroblasts isolated from scarred vocal folds (VFs) of ferrets in vitro.
Study Design
Prospective animal experiments with controls.
Methods
Scar fibroblasts (SFs) were isolated from scarred VFs that had been electrocauterized 2 weeks before harvesting (N = 4). Normal fibroblasts (NFs) were isolated from intact VFs (N = 4). SFs and NFs were incubated in the presence of 10 ng/mL transforming growth factor β1 (TGF-β1), with or without PFD. After the 48-hour incubation, mRNA expression levels of α smooth muscle actin (αSMA), TGF-β1, collagen type I, and hyaluronan synthase 2 (HAS2) were examined by real-time polymerase chain reaction. Immunohistochemistry with anti-αSMA anti-collagen type I and phosphorylated Smad (p-Smad)2/3 antibodies in SFs with or without PFD was performed. SFs and NFs were cultured in collagen gel with or without PFD for 48 hours, and the extent of gel contraction was examined quantitatively.
Results
PFD treatment significantly (P < .05) decreased mRNA expression of collagen type I, significantly increased mRNA expression of TGF-β1 and HAS2, and significantly suppressed collagen gel contraction. However, it did not have a significant effect on the expression of αSMA. The expression of p-Smad2/3 in the nucleus was faded with PFD, possibly demonstrating the suppression of translocation of p-Smad2/3 from cytoplasm to nucleus with PFD.
Conclusions
This is the first report to demonstrate the in vitro antifibrotic effects of PFD on fibroblasts isolated from scarred VFs of ferrets.
Level of evidence
NA Laryngoscope, 2017
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Teaching frontal sinus anatomy using the frontal sinus masterclass 3- D conceptualization model
Objective
Frontal sinus anatomy is complex and often is a difficult subject to both teach and learn. The traditional surgical dogma of "see one, do one, teach one" is impractical and dangerous in the frontal sinus. Based on the building block three-dimensional conceptualization module, the Frontal Sinus Masterclass (FSMC) was created to teach this anatomy.
Methods
Study was performed at two academic centers among second- to fifth-year otolaryngology residents. A pretest assessed knowledge prior to the course. Computed tomography scans of the sinuses were evaluated in triplanar view, and participants attempted to reconstruct the anatomy. Subsequently, the course instructor explained the anatomy using the building block method and showed a short video of the surgical dissection, pointing out relevant anatomy. Cases progressed in anatomical difficulty and inflammatory load. A posttest determined knowledge after the course.
Results
Thirty of 50 participating residents completed the pre- and posttests (14 junior, 16 senior residents). Correct identification of the frontal sinus drainage pathway increased from 42% to 63% correct (P = 0.054). Anatomical assessment increased from 61% to 68% correct (P = 0.047), and overall assessment increased from 52% to 66% correct (P = 0.016).
Conclusion
Objectively, participants of the FSMC expanded on their ability to recognize cells of the frontal recess on CT scans. Before the class, residents could answer less than half of the answers correctly, and by the end of the class they were answering over two-thirds of these complex questions correctly. Subjectively, participants reported benefit from the course and felt they would be better surgeons.
Level of Evidence
NA. Laryngoscope, 2017
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Does the diameter of the stapes prosthesis really matter? A prospective clinical study
Objectives/Hypothesis
To evaluate the influence of the diameter of stapes prosthesis on functional outcomes in stapes surgery.
Study Design
Prospective cohort study.
Methods
Fifty consecutive small fenestra stapedotomies performed using a 0.4-mm-diameter prosthesis were compared with 50 consecutive small fenestra stapedotomies carried out using a 0.6-mm-diameter piston. Audiological assessment following the recommendations of the Committee on Hearing and Equilibrium was performed 1 month after surgery. Postoperative complications between the two groups were noted.
Results
There were no statistically significant differences in demographic data between the two groups, and no differences in preoperative bone-conduction (BC) or air-conduction (AC) hearing thresholds for all frequencies (analysis of variance [ANOVA] and χ2 tests). No differences were found in the mean preoperative BC and AC pure-tone average and air-bone gap (ABG). In the postoperative evaluation, a statistically significant difference was found for the mean AC gain (20 ± 8.7 vs. 24 ± 11.5, P = .042, ANOVA) as well as for the postoperative AC threshold at 0.125 and 0.25 kHz and the postoperative BC threshold at 0.25 kHz (P < .01, ANOVA). A postoperative ABG ≤10 dB was obtained in 90% and 94% of patients in the 0.4-mm- and 0.6-mm-diameter piston groups, respectively (difference not significant, χ2 test). No postoperative dead ear and/or sensorineural hearing loss was noted in either group.
Conclusions
The 0.6-mm piston allowed a statistically significant higher AC gain compared with the 0.4-mm diameter piston. A larger diameter piston may be preferable if there are no anatomical or technical reasons that would favor a smaller prosthesis.
Level of Evidence
2b Laryngoscope, 2017
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Long-term outcomes in unilateral vocal fold paralysis patients
Objectives/Hypothesis
At presentation, unilateral vocal fold paralysis (UVFP) patients have different treatment options, including conservative management (CM), injection laryngoplasty (IL) with a temporary agent, or permanent medialization (PM). This study evaluates long-term outcomes for UVFP patients relative to intervention.
Study Design
Retrospective chart review.
Methods
A retrospective chart review was performed of UVFP patients who presented to the University of California San Francisco Voice and Swallowing Center. Videolaryngostroboscopy examinations were reviewed. Maximum glottic closure was quantified with the normalized glottic gap area (NGGA). Perceptual voice analysis was performed using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) at corresponding time points.
Results
Fifty-three patients met inclusion criteria. Six underwent CM only, 20 went on to require PM, 19 underwent IL only, and eight underwent IL and subsequent PM. NGGA at presentation was similar among groups; however, the CM group was noted to have more favorable CAPE-V scores for Breathiness (P = .007) and Loudness (P = .018). All groups had similar NGGA and CAPE-V scores at last follow-up. When compared to pooled data for patients who underwent PM, the IL group was noted to have similar NGGA and CAPE-V scores at presentation. Although improvements in both groups were noted following intervention, both groups appeared similar at last follow-up with the exception of Roughness, for which the IL group retained a slightly improved outcome (13.3 vs. 18.3, P = .03).
Conclusions
At presentation, UVFP patients have similar NGGA. This finding suggests that treatment recommendations cannot be made on the size of the glottic gap alone. Furthermore, in many patients, IL results in long-term benefit with glottic closure and CAPE-V scores equivalent to that obtained with PM.
Level of Evidence
4 Laryngoscope, 2017
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Investigation of the presence of HPV on KTP laser fibers following KTP laser treatment of papilloma
Objectives
Recurrent respiratory papillomatosis is often treated with in-office laser procedures using a potassium titanyl phosphate (KTP) laser transmitted through a laser fiber. Although effective, this procedure has notable downsides, including the possibility of transmitting human papillomavirus (HPV) in the smoke plume and the high cost of these single-use fibers. The objective of this study is to determine if HPV can be detected on a laser fiber after use, with or without sterilization.
Methods
Twelve patients with laryngeal papillomas were treated with KTP laser energy transmitted via a KTP fiber. Ten fibers were sterilized in CIDEX (ASP, Irvine, California), a glutaraldehyde disinfectant, for 12 minutes, whereas two fibers were left unsterilized. Human papillomavirus DNA amplification was done on all 12 fiber samples with real-time polymerase chain reaction (PCR) using general primer mediated 5+ and 6+. Human papillomavirus genotyping detection was done using type specific probes and/or Sanger sequencing.
Results
Over 27 strains of HPV were not detected on KTP fibers after use, with or without sterilization.
Conclusion
Human papillomavirus was undetectable by PCR on KTP laser fibers that were sterilized or unsterilized after use. Further studies are needed utilizing a transmission model to determine if HPV can be incubated from this fiber after sterilization.
Level of Evidence
NA. Laryngoscope, 2017
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Relationship between degree of obstruction and airflow limitation in subglottic stenosis
Objectives
Subglottic stenosis (SGS) is one of the most common airway disorders in pediatric patients. Currently, treatment decisions rely primarily on the Cotton-Myer scale, which classifies SGS severity based on percentage reduction in airspace cross-sectional area (CSA). However, the precise relationship between upper airway resistance and subglottic CSA is unknown. We hypothesize that airway resistance can be described by the Bernoulli Obstruction Theory, which predicts that airway resistance is inversely proportional to airspace CSA ( ) in cases of severe constriction.
Methods
Computed tomography (CT) scans of six healthy subjects and five SGS patients were used to create three-dimensional models of the respiratory tract from nostrils to carina. Cylindrical segments of varying lengths and varying diameters were digitally inserted in the subglottis of the healthy subjects to create simulated SGS models. Computational fluid dynamics simulations were run, and airway resistance was computed in the simulated SGS models and actual SGS models.
Results
Constriction diameter had a greater impact in airway resistance than constriction length. In agreement with the Bernoulli Obstruction Theory, airway resistance in the simulated SGS models was well represented by the power law , where
is a constant and the exponent b ranged from −0.85 to −1.07. The percentage reduction in airflow
at a constant pressure drop was found to be directly proportional to the percentage reduction in CSA
in the limit of severe constrictions, namely
, where
. Airway resistances in the simulated SGS models were similar to resistances in models based on CT scans of actual SGS patients, suggesting that our simulated SGS models were representative of airway resistance in actual SGS patients.
Conclusion
Our computer simulations suggest that the degree of airflow limitation in SGS patients may be estimated based on anatomic measurements alone. Future studies are recommended to test these predictions in larger cohorts.
Level of Evidence
4. Laryngoscope, 2017
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Oral sampling methods are associated with differences in immune marker concentrations
Objective
To determine whether the concentration and distribution of immune markers in paired oral samples were similar.
Study Type
Clinical research.
Study Design
Cross-sectional study.
Methods
Paired saliva and oral secretions (OS) samples were collected. The concentration of immune markers was estimated using Luminex multiplex assay (Thermo Fisher Scientific, Waltham, MA). For each sample, the concentration of respective immune markers was normalized to total protein present and log-transformed. Median concentrations of immune markers were compared between both types of samples. Intermarker correlation in each sampling method and across sampling methods was evaluated.
Results
There were 90 study participants. Concentrations of immune markers in saliva samples were significantly different from concentrations in OS samples. Oral secretions samples showed higher concentrations of immunoregulatory markers, whereas the saliva samples contained proinflammatory markers in higher concentration.
Conclusion
The immune marker profile in saliva samples is distinct from the immune marker profile in paired OS samples.
Level of Evidence
2b. Laryngoscope, 2017
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Epistaxis in children and adolescents with hereditary hemorrhagic telangiectasia
Objectives/Hypothesis
Our objective was to describe epistaxis onset and severity in pediatric hereditary hemorrhagic telangiectasia (HHT) patients and study the cumulative incidence of epistaxis by age of onset within each genetic subtype.
Study Design
Retrospective cohort chart review.
Methods
Charts were reviewed of patients age 0 to 18 years with a clinical or genetic diagnosis of HHT who were evaluated at a tertiary multidisciplinary HHT clinic from January 2010 to June 2016. The epistaxis severity score (ESS), a validated tool for assessing epistaxis severity, was used to assess epistaxis. Statistical analyses were conducted on the full HHT cohort as well as subgroups stratified by the HHT causative gene (HHT1 = ENG and HHT2 = ACVRL1).
Results
Sixty-nine pediatric subjects were identified; 60 had HHT confirmed by genetic testing, and nine (from families with known mutations) met published clinical diagnostic criteria alone. Fifty-nine (85%) had onset of epistaxis. The median age of onset of epistaxis was 5 years (interquartile range [IQR]: 2–9 years). The median ESS for the entire cohort was 1.6 (IQR: 0–2.6). The median ESS was higher in HHT1 versus HHT2 (2.3 vs. 1.1, P = .002), and age of epistaxis onset was earlier in HHT1 (3 vs. 5 years, P = .03). Sex and age were not associated with ESS.
Conclusions
Epistaxis may present early in HHT, but is typically mild in the pediatric period. Severity in the pediatric population is worse in patients with HHT1. By recognizing the significance of even mild, infrequent epistaxis in a child with a family history of HHT, and understanding that not all HHT patients have epistaxis during childhood, community providers and otolaryngologist can assist in the early detection of HHT.
Level of Evidence
4 Laryngoscope, 2017
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Bodycontouring beim Mann
Zusammenfassung
Verfahren der Körperformung werden bei Männern immer häufiger eingesetzt. Die Jahresstatistiken der International Society of Aesthetic Plastic Surgery (ISAPS) belegen diese Entwicklung. Etwa 20 % der Patienten, die sich weltweit einer Körperformung unterziehen, sind Männer. Für gute Behandlungsergebnisse und im Sinne der Sicherheit ist es wichtig, die Besonderheiten der männlichen Anatomie zu kennen und sie bei der Operationsplanung sowie bei der Festlegung der Inzisionslinien zu berücksichtigen. Im vorliegenden Beitrag werden die geschlechtsspezifischen Unterschiede herausgestellt, insbesondere in Bezug auf die Abdominoplastik.
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Perspectives in allergen immunotherapy: 2017 and beyond
Abstract
The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalised AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase III studies in the field, the future role of allergen exposure chambers in AIT-studies, and specific considerations in performing AIT-studies in the paediatric population.
Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardisation of practice in the treatment of allergies. This supplement presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.
This article is protected by copyright. All rights reserved.
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The impact of speech and language problems in kindergarten on academic learning and special education status in grade three
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Cisplatin triggers cancer stem cell enrichment in platinum-resistant cells through NF-κB-TNFα-PIK3CA loop
Parallel to complex alteration in molecular and cellular events, enrichment of cancer stem cells (CSC) contributes significantly in deliberation and maintenance of cisplatin resistance. Cisplatin mediated CSC ...
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Hypermethylation and loss of retinoic acid receptor responder 1 expression in human choriocarcinoma
Human placental development resembles tumorigenesis, due to the invasive and fusogenic potential of trophoblasts. However, these features are tightly controlled in trophoblasts. Disturbance of this spatial and...
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ID1 promotes hepatocellular carcinoma proliferation and confers chemoresistance to oxaliplatin by activating pentose phosphate pathway
Drug resistance is one of the major concerns in the treatment of hepatocellular carcinoma (HCC). The aim of the present study was to determine whether aberrant high expression of the inhibitor of differentiati...
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Das Ringerohr der etwas anderen Art
Zusammenfassung
Wir berichten über den Fall eines 19-jährigen Mannes mit rezidivierenden, kreisförmigen und groblamellär geschuppten Hautveränderungen. Anamnestisch war der Patient in seiner Freizeit als Ringer tätig. Nach zunächst frustraner antibiotischer Lokaltherapie konnte im Rahmen einer spezifischen dermatologischen Diagnostik eine Tinea corporis gladiatorum gesichert werden. Unter der leitliniengerechten Therapie für Dermatophytosen mittels systemischer Gabe von Fluconazol sowie einer Lokaltherapie mit Ciclopiroxolamin und Ketoconazol konnte eine schnelle Befundbesserung erwirkt werden.
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Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus
Abstract
Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF-ĸB). We report the case of a 6-month-old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF-ĸB, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.
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Anodal transcranial direct current stimulation over left inferior frontal gyrus enhances sentence comprehension
Publication date: January 2018
Source:Brain and Language, Volume 176
Author(s): Beatrice Giustolisi, Alessandra Vergallito, Carlo Cecchetto, Erica Varoli, Leonor J. Romero Lauro
We tested the possibility of enhancing natural language comprehension through the application of anodal tDCS (a-tDCS) over the left inferior frontal gyrus, a key region for verbal short-term memory and language comprehension. We designed a between subjects sham- and task-controlled study. During tDCS stimulation, participants performed a sentence to picture matching task in which targets were sentences with different load on short-term memory. Regardless of load on short-term memory, the Anodal group performed significantly better than the Sham group, thus providing evidence that a-tDCS over LIFG enhances natural language comprehension.To our knowledge, we apply for the first time tDCS to boost sentence comprehension.This result is of special interest also from a clinical perspective: applying a-tDCS in patients manifesting problems at the sentence level due to brain damage could enhance the effects of behavioral rehabilitation procedures aimed to improve language comprehension.
Graphical abstract
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