Drain-free parotidectomy: a pilot study using ARTISS fibrin sealant.

PURPOSE: Parotidectomy is the definitive procedure for diagnosis and treatment of most parotid masses but, due to the risk of haematoma and seroma formation, has traditionally included a drain. The drain itself comes with its own risks and, in most hospitals, the need for overnight admission, which has significant cost implications (Mallon et al. Ann R Coll Surg Engl 95(4):258-262; 2013). Fibrin glue, with its haemostatic and adhesive properties, reduces the risk of collection or haematoma and therefore may negate the need for a drain. This is the first study to look at the use of ARTISS as an alternative to drains in parotidectomy. METHODS: We performed a retrospective study of all the patients who underwent a partial parotidectomy over a 4-year period from 2014 until 2018 under the same senior surgeon. Patients were divided into those that had a drain and those that had ARTISS. Their operative record, inpatient notes and clinic letters were reviewed to record information regarding length of stay, histology, complications and recurrence. RESULTS: A total of 34 patients were identified; 17 ARTISS and 17 drain patients. We showed that the mean length of stay improved significantly from 1.6 days with the drain to 0.5 days with ARTISS (Fig. 1) but without a difference in complication rate (Fig. 2), which was 5/17 (29%) in each group. CONCLUSIONS: In conclusion, parotidectomy can be undertaken safely as a day-case procedure with the application of ARTISS. This new approach to parotid surgery not only offers less morbidity for patients but also positive financial revenue for public health institutions.

Clinical trials and registries in haemophilia: Opponents or collaborators? Comparison of PUP data derived from different data sources.

INTRODUCTION: The "Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products" (ClinGL) provides the requirements for the performing of clinical trials (CTs) for marketing authorization in Europe. The number of eligible previously untreated patients (PUPs) for CTs might be difficult to meet because of the concurrent development of FVIII concentrates, and additional data sources must be explored. AIM: The extent to which CTs and the PedNet registry met relevant parameters, identified in the ClinGL, as well as inhibitor incidences were investigated in patients from both sources. METHODS: Anonymized data of eight CTs in 369 PUPs performed from 1987 to 2009 were compared with each other and with 632 PUPs (born 2000-2009) from PedNet. RESULTS: Clinical trials in PUPs performed for marketing authorization were too heterogeneous in their investigated parameters; therefore, a comparison of single factor concentrates was not possible. Data collection in PedNet met relevant parameters required for PUPs in accordance with the ClinGL. The overall inhibitor incidences were comparable (CT = 30.9% vs PedNet = 30.6%) when only severe haemophilia A (HA) patients from both data sources were considered. CONCLUSIONS: Previously performed CTs in PUPs were divergent, which prevented a direct comparison of outcomes. However, this study demonstrated that data from CTs and carefully designed registries may complement each other in the establishing of sufficient safety information for single products to improve clinical insights and support regulatory decisions.

Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32-q27.2.

Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32.

Kreuth IV: European consensus proposals for treatment of haemophilia with coagulation factor concentrates.

INTRODUCTION: This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the 'Kreuth IV' meeting in May 2016. AIM: The objective of the meeting was for experts in the field of haemophilia from across Europe to draft resolutions regarding current issues relating to the treatment of haemophilia. RESULTS: Hospitals providing clinical care for people with haemophilia and related disorders are strongly recommended to seek formal designation as either European Haemophilia Treatment Centres (EHTC) or European Haemophilia Comprehensive Care Centres (EHCCC). There should be agreed national protocols or guidelines on management of the ageing patient with haemophilia. The minimum consumption of factor VIII and IX concentrate in any country should be 4 IU and 0.5 IU per capita of general population respectively. Treatment for hepatitis C with direct-acting antiviral agents should be provided to all people with haemophilia on a priority basis. Genotype analysis should be offered to all patients with severe haemophilia. Genetic counselling, when given, should encompass the recommendation that genetic relatives of the affected person be advised to seek genetic counselling. People with inhibitors should have access to bypassing agents, immune tolerance and elective surgery. National or regional tenders for factor concentrates are encouraged. Outcome data including health related quality of life should be collected. Treatment with extended half-life factors should be individualized and protection against bleeding should be improved by increasing trough levels. Steps should be taken to understand and minimize the risk of inhibitor development. CONCLUSION: It is hoped that these recommendations will help to foster equity of haemophilia care throughout Europe.

Multidimensional operando analysis of macroscopic structure evolution in lithium sulfur cells by X-ray radiography.

Lithium sulfur cells are the most promising candidate for the post lithium-ion battery era. Their major drawback is rapid capacity fading attributed to the complex electrochemical processes during charge and discharge which are not known precisely. Here we present for the first time a multidimensional operando measurement by combining X-ray radiography with impedance spectroscopy while galvanostatically charging and discharging a lithium sulfur cell. The formation of macroscopic sulfur crystals at the end of charge can be seen directly by X-ray radiography. These crystals can be assigned to stable α-sulfur (rhombic) and metastable ß-sulfur (monoclinic) by their characteristic crystal habit. These crystal structures with a length of more than 1 mm form and dissolve rapidly during cycling. Their appearance is accompanied by characteristic signals in impedance spectroscopy. Macroscopic crystals of Li2S cannot be observed in full agreement with earlier studies by operando X-ray diffraction. In addition, X-ray radiography reveals non-wetted areas on the carbon cathode. These regions grow during discharge and are reduced during charge. The area of these electrochemically inactive spots is inversely proportional to discharge capacity.

Neutron guide optimisation for a time-of-flight neutron imaging instrument at the European Spallation Source.

A neutron transport system for the planned imaging instrument ODIN at the future European Spallation Source (ESS) based on neutron optical components was designed and optimized. Different ways of prompt pulse suppression were studied. The spectral performance of the optimal neutron guide configuration is presented. In addition, the influence of the gaps in the guide system needed for the required chopper configuration was investigated. Given that the requirements for an imaging instrument located on a long guide system and hosting a complex chopper system are extremely demanding in terms of spectral and divergence needs, this study can be beneficial for a wide range of instruments in various ways.

Research in haemophilia B--approaching the request for high evidence levels in a rare disease.

Payers in European countries request studies with high levels of evidence for decision making also for rare diseases like haemophilia B (HB). The objective of the study was to determine the status quo of current studies in HB regarding the overall level of evidence generated. The methods used for performing the study were systematic literature research in EMBASE and MEDLINE, search terms 'HB' and 'factor IX' (FIX). The inclusion criteria were journal articles (JA), conference abstracts (CA), English language, published between January 2009 and March 2013, studies only; screening of titles, abstracts, full texts subsequently. ClinicalTrials.gov search: unpublished registered trials (RT) concerning HB or FIX. The analysis was performed on research topic, sponsor, recruitment status and study design. Screening of 1639 hits yielded 31 JA describing 35 studies, and 62 CA. FIX was subject of 21 studies (60.0%) and 29 CA (46.8%). Seven studies focused on various aspects of HB, six on haemophilia studies with separate HB data. Screening of 173 hits from ClinicalTrials.gov yielded 42 RT. Overall, 32 RT (76.2%) related to FIX. Measurement of health-related quality of life (HRQoL) was identified in none of these studies, four CA (6.5%), four RT (9.5%). Randomized study design was found in one study (2.9%), four RT (9.5%). Three studies (8.6%) and seven RT (16.7%) were prospective, observational and comparative. The majority of published clinical studies do not meet payers' expectations for evidence. Therefore, clinical investigation concepts addressing randomization, outcomes research including HRQoL and comparison of therapy options should be discussed. Refined statistical methods and exploitation of complementary real-life data sources may fill current evidence gaps concerning rare diseases.

Kreuth III: European consensus proposals for treatment of haemophilia with coagulation factor concentrates.

This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the Kreuth III meeting in April 2013. To optimize the organization of haemophilia care nationally, it is recommended that a formal body be established in each country to include the relevant clinicians, national haemophilia patient organization, health ministry, paying authority and (if appropriate) regulatory authorities. The minimum factor VIII consumption level in a country should be 3 I.U. per capita. Decisions on whether to adopt a new product should not be based solely on cost. Prophylaxis for children with severe haemophilia is already recognized as the optimum therapy. Ongoing prophylaxis for individual adults should also be provided when required based on clinical decision making by the clinician in consultation with the patient. Children with inhibitors who have failed, or who are not suitable for, immune tolerance therapy should be offered prophylaxis with bypassing agents. Single factor concentrates should be used as therapy wherever possible in patients with rare bleeding disorders. Orphan drug designation for a factor concentrate should not be used to hinder the development, licencing and marketing of other products for the same condition which have demonstrably different protein modification or enhancement.

Airway emergency from spontaneous haemorrhagic thyroid cancer.

Spontaneous thyroid haemorrhages are rare. There are reported cases occurring in thyroid nodules and cysts but none in thyroid malignancies. We describe a 48 year old who presented to the on-call ENT team with a rapidly progressing neck swelling that was interfering with his airway. After resuscitation, the patient underwent a right lobectomy to stop the bleeding. Histology showed a thyroid follicular carcinoma. As per the regional multidisciplinary team discussion, he underwent a completion thyroidectomy followed by radioactive iodine treatment. We conclude that spontaneous haemorrhages of the thyroid gland can occur in malignancies and stress the importance of early histological diagnosis.

Estimation of snag carbon transfer rates by ecozone and lead species for forests in Canada.

Standing dead trees (snags) and downed woody debris contribute substantially to the carbon (C) budget of Canada's forest. Accurate parameterization of the C transfer rates (CTRs) from snags to downed woody debris is important for forest C dynamics models such as the Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3), but CTRs are rarely measured or reported in the literature. Therefore, forest C models generally use snag fall rates (FRs) available in the literature, as a proxy for CTRs. However, FRs are based on stem counts while CTRs refer to mass transfers. Stem mass and stem number are not linearly related, with small diameter trees representing disproportionately lower C mass transfers. Therefore this proxy, while convenient, may bias C transfer from standing dead to downed woody material. Here, we combined tree data from 10802 sample plots and previously published species-specific individual-tree relationships between tree diameter (diameter at breast height, dbh) and fall rate to derive stand-level estimates of CTRs for the CBM-CFS3. We estimated CTRs and FRs and used the FR values to validate this approach by comparing them with standardized FR values compiled from the literature. FRs generally differed from CTRs. The overall CTR (4.78% +/- 0.02% per year, mean +/- SE) was significantly smaller than the overall FR (5.40% +/- 0.02% per year; mean +/- SE). Both the difference between FR and CTR (FR - CTR) and the CTR itself varied by ecozone, with ecozone means for CTR ranging from 3.94% per year to 10.02% per year. This variation was explained, in part, by heterogeneity in species composition, size (dbh distribution), structure, and age of the stands. The overall mean CTR estimated for the Snag_Stemwood (4.78% per year) and the Snag_Branches (11.95% per year) pools of the CBM-CFS3 were approximately 50% and 20% higher than the current default rates used in the CBM-CFS3 of 3.2% and 10.0%, respectively. Our results demonstrate that using CTRs to estimate the annual C transfer from standing dead trees to downed woody biomass will yield more accurate estimates of C fluxes than using a FR proxy, and this accuracy could be further improved by accounting for differences in ecozone, stand component (hardwood or softwood), or lead species.

Correlation of GREB1 mRNA with protein expression in breast cancer: validation of a novel GREB1 monoclonal antibody.

Studies of gene regulated by estrogen in breast cancer 1 (GREB1) have focused on mRNA levels with limited evidence about GREB1 protein expression in normal and breast cancer cells. A monoclonal antibody that recognizes GREB1 protein in breast tissues could be applied to correlate protein expression with established mRNA expression data. A hybridoma expressing a murine monoclonal antibody targeting a 119 amino acid peptide specific to human GREB1 was generated. The novel monoclonal GREB1 antibody (GREB1ab) was validated for use in Western blotting as well as immunohistochemical (IHC) applications. GREB1ab detects a 216 kDa protein corresponding to GREB1 in estrogen receptor alpha (ERalpha+) breast cancer cells as well as ERalpha- breast cancer cells transduced with a GREB1 expression vector. GREB1ab specificity was verified using an ERalpha antagonist to prevent GREB1 induction as well as a silencing siRNA targeting GREB1 mRNA. GREB1ab was further validated for detection of GREB1 by IHC in breast cancer cell lines and breast tissue microarrays (TMA). ERalpha+ cell lines were observed to express GREB1 while ERalpha- cell lines did not express detectable levels of the protein. Using breast cancer tissue whole sections, IHC with the GREB1ab identified protein expression in ERalpha+ breast cancer tissue as well as normal breast tissue, with little GREB1 expression in ERalpha- breast cancer tissue. Furthermore, these data indicate that GREB1 mRNA expression correlates well with protein expression. The novel monoclonal GREB1ab is specific for GREB1 protein. This antibody will serve as a tool for investigations focused on the expression, distribution, and function of GREB1 in normal breast and breast cancer tissues.

Tensorial neutron tomography of three-dimensional magnetic vector fields in bulk materials.

Knowing the distribution of a magnetic field in bulk materials is important for understanding basic phenomena and developing functional magnetic materials. Microscopic imaging techniques employing X-rays, light, electrons, or scanning probe methods have been used to quantify magnetic fields within planar thin magnetic films in 2D or magnetic vector fields within comparable thin volumes in 3D. Some years ago, neutron imaging has been demonstrated to be a unique tool to detect magnetic fields and magnetic domain structures within bulk materials. Here, we show how arbitrary magnetic vector fields within bulk materials can be visualized and quantified in 3D using a set of nine spin-polarized neutron imaging measurements and a novel tensorial multiplicative algebraic reconstruction technique (TMART). We first verify the method by measuring the known magnetic field of an electric coil and then investigate the unknown trapped magnetic flux within the type-I superconductor lead.

Floccular fossa size is not a reliable proxy of ecology and behaviour in vertebrates.

The cerebellar floccular and parafloccular lobes are housed in fossae of the periotic region of the skull of different vertebrates. Experimental evidence indicates that the lobes integrate visual and vestibular information and control the vestibulo-ocular reflex, vestibulo-collic reflex, smooth pursuit and gaze holding. Multiple paleoneuroanatomy studies have deduced the behaviour of fossil vertebrates by measuring the floccular fossae (FF). These studies assumed that there are correlations between FF volume and behaviour. However, these assumptions have not been fully tested. Here, we used micro-CT scans of extant mammals (47 species) and birds (59 species) to test six possible morphological-functional associations between FF volume and ecological/behavioural traits of extant animals. Behaviour and ecology do not explain FF volume variability in four out of six variables tested. Two variables with significant results require further empirical testing. Cerebellum plasticity may explain the lack of statistical evidence for the hypotheses tested. Therefore, variation in FF volume seems to be better explained by a combination of factors such as anatomical and phylogenetic evolutionary constraints, and further empirical testing is required.

The growing number of hemophilia registries: Quantity vs. quality.

Registries for rare diseases provide a tool for obtaining an overview of the clinical situation and can be used to discover points of improvement and to monitor long-term safety. Registries could also become a powerful tool to provide supporting information for marketing authorization. There is an urgent need for a pan-European or global strategy that supports consistent data. Therefore, transparency in data collection, harmonization of the database structures, and the convergence of scientific approaches are required.

Degradation of Li/S Battery Electrodes On 3D Current Collectors Studied Using X-ray Phase Contrast Tomography.

Lithium/sulphur batteries are promising candidates for future energy storage systems, mainly due to their high potential capacity. However low sulphur utilization and capacity fading hinder practical realizations. In order to improve understanding of the system, we investigate Li/S electrode morphology changes for different ageing steps, using X-ray phase contrast tomography. Thereby we find a strong decrease of sulphur loading after the first cycle, and a constant loading of about 15% of the initial loading afterwards. While cycling, the mean sulphur particle diameters decrease in a qualitatively similar fashion as the discharge capacity fades. The particles spread, migrate into the current collector and accumulate in the upper part again. Simultaneously sulphur particles lose contact area with the conducting network but regain it after ten cycles because their decreasing size results in higher surface areas. Since the capacity still decreases, this regain could be associated with effects such as surface area passivation and increasing charge transfer resistance.

Computer instruction in learning concepts of streptococcal pharyngitis.

OBJECTIVE: To evaluate a computer-assisted instruction unit covering the basic concepts of streptococcal pharyngitis for effectiveness as a learning tool. DESIGN: Randomized control trial. SETTING: A medical school associated with a tertiary care hospital. PARTICIPANTS: Third-year medical students on a pediatric clerkship from December 1, 1992, to October 31, 1993. INTERVENTION: Students were randomized into a study or a control group and given a pretest on streptococcal pharyngitis. The study group then completed the computer-assisted instruction unit. No attempt was made to distinguish among the clinical experiences of the two groups during the next 4 weeks, after which a second test on streptococcal pharyngitis was given to both groups. MAIN OUTCOME MEASURES: Outcome was measured by scores (percentage correct) from tests given at day 1 and week 4 of the clerkship. RESULTS: The posttest scores of the study group increased by an average of 12.1 above the pretest scores, but the scores of the control group were only 3.4 points higher. The difference between these increases is statistically significant (P < .01, Student's t test). CONCLUSION: Short, well-designed computer-assisted instruction units can be effective tools in medical education.

The possible relationship between transient evoked otoacoustic emissions and organ of Corti irregularities in the guinea pig.

Otoacoustic emissions are believed to arise from an active process associated with the outer hair cells in the mammalian organ of Corti. They have been attributed to the presence of impedance discontinuities on the basilar membrane which might be caused by hair cell irregularities. To test this hypothesis we have investigated the possible relationship between transient evoked otoacoustic emissions (TEOAEs) and anatomical integrity in the organ of Corti. Click-evoked TEOAEs have been measured from the ear canals of normal, pigmented guinea pigs using an Otodynamics ILO88 analyser. Emissions were present in 18 out of 19 animals tested and the major frequencies observed were consistently present in different measurements over periods of up to ten weeks provided recording conditions were satisfactory. The frequency spectra of the TEOAEs resembled those measured in humans but the latencies of the responses were considerably shorter. In one acute experiment, the TEOAEs were shown to be dependent on metabolic energy as they were lost rapidly following termination with an overdose of anaesthetic. In another case, evoked emissions of long duration (sustained) at about 1 kHz were obtained from both ears. All cochleae examined showed irregularities, especially patches of mainly apical outer hair cell loss of differing extents. However, there was no evidence that substantial lesions coincided consistently with the frequency regions corresponding to the major emissions. Nevertheless, it was noted that the total energy level of emissions was proportional to the total outer hair cell loss, except in one case, where the outer hair cell loss was substantial and the energy level of TEOAEs was considerably lower. Although there is no clear relationship between TEOAEs of specific frequencies and abnormalities at the corresponding cochleotopic location in the organ of Corti which could represent impedance discontinuities, the degree of irregularity may determine the overall emission level. This finding is consistent with the idea that emissions arise as a result of irregularity producing variations in the reflection coefficient.

Adenocarcinoma of the larynx--a distant metastasis from a rectal primary.

Laryngeal metastases from remote primary tumours are uncommon. They derive mostly from melanomas or renal cell carcinomas. The generally rare laryngeal adenocarcinomas can only be classified as metastatic tumours in the presence of a distant primary of the same histology. Only five cases of a laryngeal secondary originating from adenocarcinoma of the large bowel have been reported in the world literature. A further case is presented which to our knowledge is the first to arise from the rectum, a site which suggests haematogenous tumour spread. This paper emphasizes the need for the search of synchronous metastatic disease and discusses the therapeutic options on the grounds of current management of singular colorectal secondaries.