Practice patterns in management of differentiated thyroid cancer since the 2014 British Thyroid Association (BTA) guidelines.

BACKGROUND: The updated 2014 BTA guidelines emphasised a more conservative, risk adapted model for the management of low-risk differentiated thyroid cancer (DTC). In comparison to historical approach of total thyroidectomy combined with radioactive iodine, treatment de-escalation is increasingly supported. AIMS: To evaluate the impact of the updated BTA guidelines on the management of DTC cases at regional UK centre. METHODS: All DTC patients were retrospectively identified from regional thyroid MDT database between Jan2009-Dec2020. Oncological treatment and clinico-pathological characteristics were analysed. RESULTS: 623 DTC cases were identified; 312 (247 female: 65 male) between 2009 and 2014 and 311 (225 female: 86 male) between 2015 and 2020. Median age is 48 years (range 16-85). By comparing pre- and post-2015 cohorts, there was a significant drop in total thyroidectomy (87.1% vs 76.8%, p = 0.001) and the use of radioactive iodine (RAI) (73.1% vs 62.1%, p = 0.003) in our post-2015 cohort. When histological adverse features were analysed, extra-thyroidal extension (4.2% vs 17.0%, p=< 0.001), lymphovascular invasion (31.4% vs 50.5%, p=<0.001) and multi-centricity (26.9% vs 43.4%, p = 0.001) were significantly increased in the post 2015 cohort. Nonetheless, total thyroidectomy (TT) remains the treatment choice for low risk T1/2 N0 M0 disease in 65.3% (124/190) in post-2015 cohort for several reasons. Reasons include adverse histological features (50.8%), benign indications (32.5%), contralateral nodules (11.7%), patient preference (2.5%), and diagnostic uncertainty (2.5%). CONCLUSION: Our study confirms a move towards a more conservative approach to patients with low-risk DTC in the UK, which is in keeping with the BTA 2014 guideline and international trends, but total thyroidectomy remains prevalent for low risk T1/2 N0 M0 disease for other reasons.

Introducing ethanol ablation as a treatment for thyroid cysts in the emergency setting.

BACKGROUND: Ethanol ablation for the treatment of thyroid cysts has been well documented in the literature as a safe, effective treatment option in the elective setting. This study demonstrates the use of ethanol ablation in the emergency setting. METHODS: Three patients presenting with airway-threatening compressive symptoms secondary to a thyroid cyst were treated with ethanol ablation within 24 hours of presentation to hospital. RESULTS: All patients had symptom resolution at a median of nine months follow up post procedure. Sixty-six per cent of patients required only one treatment. There was a median of 100 per cent radiological resolution of the cystic component. The median Glasgow Benefit Inventory score was +27.7, similar to that for tonsillectomy. CONCLUSION: Ethanol ablation is a safe, cost-effective and efficient treatment option for thyroid cysts in the acute setting.

A balancing act: changing the referral pathway following remote consultations for dizziness during the coronavirus disease 2019 pandemic.

BACKGROUND: This paper reports our experience in managing dizzy patients remotely during the coronavirus disease 2019 pandemic, and explored its safety as an alternative to face-to-face consultations. METHODS: Dizzy patients referred by their general practitioner were contacted to answer a validated questionnaire. Clinicians recorded the time needed for consultations, and the diagnosis at each of the following assessment stages: after review of the electronic general practitioner letter; following completion of the questionnaire; following the telephone consultation; and/or at follow up. Patients were telephoned no earlier than three months later to determine satisfaction with the service and symptom resolution. Electronic patient records were checked for presentation to hospital because of dizziness. RESULTS: Seventy patients had telephone consultations. None presented to the emergency department or were admitted. The majority of consultations took 15-30 minutes. The most diagnosed condition was benign positional paroxysmal vertigo. Seventy-nine per cent of patients were satisfied with the service. The questionnaire and telephone consultations demonstrated the greatest diagnosis agreement (κ = 0.40). CONCLUSION: Validated questionnaire and telephone consultations are a safe alternative to face-to-face consultations. Our patient referral pathway has now changed to include elements of the questionnaire.

Transnasal humidified rapid-insufflation ventilatory exchange ('THRIVE') in the coronavirus disease 2019 pandemic.

BACKGROUND: Since the start of the coronavirus disease 2019 pandemic, transnasal humidified rapid-insufflation ventilatory exchange ('THRIVE') has been classified as a high-risk aerosol-generating procedure and is strongly discouraged, despite a lack of conclusive evidence on its safety. METHODS: This study aimed to investigate the safety of transnasal humidified rapid-insufflation ventilatory exchange usage and its impact on staff members. A prospective study was conducted on all transnasal humidified rapid-insufflation ventilatory exchange cases performed in our unit between March and July 2020. RESULTS: During the study period, 18 patients with a variety of airway pathologies were successfully managed with transnasal humidified rapid-insufflation ventilatory exchange. For each case, 7-10 staff members were present. Appropriate personal protective equipment protocols were strictly implemented and adhered to. None of the staff involved reported symptoms or tested positive for coronavirus disease 2019, up to at least a month following their exposure to transnasal humidified rapid-insufflation ventilatory exchange. CONCLUSION: With strictly correct personal protective equipment use, transnasal humidified rapid-insufflation ventilatory exchange can be safely employed for carefully selected patients in the current pandemic, without jeopardising the health and safety of the ENT and anaesthetic workforce.

Clinicopathological features of Differentiated Thyroid Cancer presenting in the UK versus internationally: An observational cohort study.

INTRODUCTION: Very little data are available regarding differentiated thyroid cancer (DTC) managed in the UK, and no UK patients are included in the evidence base upon which international guidelines are based. Therefore, the aim of this study was to compare the clinicopathological features of patients with DTC presenting in a UK population with international patient cohorts. PATIENTS AND METHODS: Data were collected from a prospectively held multi-disciplinary team records from January 2009 to December 2016. The local cohort was compared with cohorts from across the world based on clinicopathological features. Ethical approval was obtained by Lothian Caldicott Guardian (Ref 16 133). RESULTS: 444 cases were diagnosed locally with a median age of 48 years (range 16-86 years). 78% of patients were female. 25% of our patients had follicular carcinoma with an overall N1 rate of 20%. Distant disease was recorded in 5% cases. In comparison with international data, our local cohort had a higher rate of follicular thyroid carcinoma. Variation was seen in terms of age, gender distribution, primary tumour size, nodal and distant disease. In Korea, where thyroid cancer screening has been undertaken, smaller tumours, higher rates of nodal disease and lower rates of distant disease are described. CONCLUSION: In our centre, a higher rate of males is treated with larger primary disease and a higher percentage of follicular carcinoma. The reasons for this geographic variation in clinicopathological features in the UK are unclear. As a result, caution should be applied in translating the international move towards a more conservative approach to DTC in the UK in comparison with other areas of the world.

Oncological outcomes in differentiated thyroid cancer in South East Scotland.

BACKGROUND: Differentiated thyroid cancer (DTC) is increasing in incidence but little is known about oncological outcomes for patients treated in the UK. Internationally there is a move toward conservative treatment of DTC. However, this is based on evidence from outside the UK. The aim of this study was to analyse oncological outcomes for a contemporary cohort of patients treated in a UK centre. METHODS: Review of 470 consecutive prospectively recorded cases of DTC from the South East of Scotland endocrine MDT 2009-2018. Data on patient, tumour and treatment details as well as recurrence and survival details were extracted from the electronic patient record. RESULTS: Of 470 patients female:male ratio was 3.4:1, median age at presentation was 48 years (range 16-86 years). Overall 193 (41%), 134 (29%), 119 (25%) and 22 (5%) patients were p T1, T2, T3, and p T4 respectively. 385 patients (82%) were pN0, 31 patients (7%) were pN1a and 53 patients (11%) were pN1b. 19 patients (4%) were M1. Of 470 patients 350 (74%) had papillary thyroid carcinoma, 120 patients (26%) had follicular carcinoma. Surgical management was lobectomy, isthumusectomy, total thyroidectomy and lobectomy then completion thyroidectomy in 14%,1%, 41% and 43% cases respectively. 64% patients received radioactive Iodine (RAI) therapy. With a median follow-up of 70 months (range 4-124 months), 5 years overall survival and disease specific survival were 96.7% and 98.5% respectively. The 5 year local recurrence free survival (LRFS), regional recurrence free survival (RRFS), locoregional recurrence free survival (LRRFS), distant recurrence free survival (DRFS) and any recurrence free survivals were 100%, 95.8%, 95.8%, 98.3% and 95% respectively. CONCLUSION: Oncological outcomes for patients treated with DTC were excellent, in keeping with experience from international groups, suggesting that a move towards conservative treatment in the UK seems reasonable.

Spiral T1 Spin-Echo for Routine Postcontrast Brain MRI Exams: A Multicenter Multireader Clinical Evaluation.

BACKGROUND AND PURPOSE: Spiral MR imaging has several advantages compared with Cartesian MR imaging that can be leveraged for added clinical value. A multicenter multireader study was designed to compare spiral with standard-of-care Cartesian postcontrast structural brain MR imaging on the basis of relative performance in 10 metrics of image quality, artifact prevalence, and diagnostic benefit. MATERIALS AND METHODS: Seven clinical sites acquired 88 total subjects. For each subject, sites acquired 2 postcontrast MR imaging scans: a spiral 2D T1 spin-echo, and 1 of 4 routine Cartesian 2D T1 spin-echo/TSE scans (fully sampled spin-echo at 3T, 1.5T, partial Fourier, TSE). The spiral acquisition matched the Cartesian scan for scan time, geometry, and contrast. Nine neuroradiologists independently reviewed each subject, with the matching pair of spiral and Cartesian scans compared side-by-side, and scored on 10 image-quality metrics (5-point Likert scale) focused on intracranial assessment. The Wilcoxon signed rank test evaluated relative performance of spiral versus Cartesian, while the Kruskal-Wallis test assessed interprotocol differences. RESULTS: Spiral was superior to Cartesian in 7 of 10 metrics (flow artifact mitigation, SNR, GM/WM contrast, image sharpness, lesion conspicuity, preference for diagnosing abnormal enhancement, and overall intracranial image quality), comparable in 1 of 10 metrics (motion artifacts), and inferior in 2 of 10 metrics (susceptibility artifacts, overall extracranial image quality) related to magnetic susceptibility (P < .05). Interprotocol comparison confirmed relatively higher SNR and GM/WM contrast for partial Fourier and TSE protocol groups, respectively (P < .05). CONCLUSIONS: Spiral 2D T1 spin-echo for routine structural brain MR imaging is feasible in the clinic with conventional scanners and was preferred by neuroradiologists for overall postcontrast intracranial evaluation.

Do we need to worry about eating wheat?

Wheat is a staple food throughout the temperate world and an important source of nutrients for many millions of people. However, the last few years have seen increasing concerns about adverse effects of wheat on health, particularly in North America and Europe, with the increasing adoption of wheat-free or gluten-free diets. This relates to two concerns: that wheat products are disproportionally responsible for increases in obesity and type 2 diabetes and that wheat gluten proteins cause a range of adverse reactions, including allergies, coeliac disease and 'non-coeliac gluten sensitivity'. The first concern has been refuted in previous publications, and we therefore focus on the second here. Current evidence indicates that allergy to ingested wheat and coeliac disease (and related intolerances) each occur in up to 1% of the population. The extent to which their prevalence has increased is difficult to quantify due to improved diagnosis and increased awareness. However, neither appears to be increasing disproportionally when compared with other immunologically mediated adverse reactions to food. Other adverse reactions to wheat are more difficult to define as their mechanisms are not understood and they are therefore difficult to diagnose. In particular, 'non-coeliac wheat sensitivity' has been reported to occur in 6% or more of the population in the US. However, the application of more rigorous diagnostic criteria is likely to give substantially lower estimates of prevalence. It is therefore unlikely that the health of more than a small proportion of the population will be improved by eliminating wheat or gluten from the diet. In fact, the opposite may occur as wheat is an important source of protein, B vitamins, minerals and bioactive components.

A systematic review on skin complications of bone-anchored hearing aids in relation to surgical techniques.

A systematic review to study the skin complications associated with the bone-anchored hearing aid in relation to surgical techniques. The following databases have been searched: MEDLINE, EMBASE, the Cochrane Library , Google scholar and the PubMed. The literature search date was from January 1977 until November 2013. Randomised controlled trials and retrospective studies were included. Initial search identified 420 publications. Thirty articles met the inclusion criteria of this review. The most common surgical techniques identified were full-thickness skin graft, Dermatome and linear incision techniques. The result shows that dermatome technique is associated with higher rate of skin complications when compared to linear incision and skin graft techniques. Based on the available literature, the use of a linear incision technique appears to be associated with lower skin complications; however, there is limited data available supporting this. Higher quality studies would allow a more reliable comparison between the surgical techniques.

Towards optimized MR thermometry of the human heart at 3T.

Catheter ablation using radio frequency (RF) has been used increasingly for the treatment of cardiac arrhythmias and may be combined with proton resonance frequency shift (PRFS) -based MR thermometry to determine the therapy endpoint. We evaluated the suitability of two different MR thermometry sequences (TFE and TFE-EPI) and three blood suppression techniques. Experiments were performed without heating, using an optimized imaging protocol including navigator respiratory compensation, cardiac triggering, and image processing for the compensation of motion and susceptibility artefacts. Blood suppression performance and its effect on temperature stability were evaluated in the ventricular septum of eight healthy volunteers using multislice double inversion recovery (MDIR), motion sensitized driven equilibrium (MSDE), and inflow saturation by saturation slabs (IS). It was shown that blood suppression during MR thermometry improves the contrast-to-noise ratio (CNR), the robustness of the applied motion correction algorithm as well as the temperature stability. A gradient echo sequence accelerated by an EPI readout and parallel imaging (SENSE) and using inflow saturation blood suppression was shown to achieve the best results. Temperature stabilities of 2 °C or better in the ventricular septum with a spatial resolution of 3.5 × 3.5 × 8mm(3) and a temporal resolution corresponding to the heart rate of the volunteer, were observed. Our results indicate that blood suppression improves the temperature stability when performing cardiac MR thermometry. The proposed MR thermometry protocol, which optimizes temperature stability in the ventricular septum, represents a step towards PRFS-based MR thermometry of the heart at 3 T.

Simultaneous T1 measurements and proton resonance frequency shift based thermometry using variable flip angles.

A method is presented which allows precise temperature and longitudinal (T(1)) relaxation time measurements with high spatial and temporal resolution. This is achieved by combining dynamic variable flip angle based T(1) relaxation mapping with proton resonance frequency shift based thermometry. Herein, dynamic T(1) mapping is either used as a complementary measure of temperature or for the detection of T(1) contrast agent release. For the first application, the temperature evolution during a high-intensity focused ultrasound tissue ablation experiment was measured in both, porcine fat and muscle, simultaneously. In this application, temperature accuracies of 2.5 K for T(1)-based thermometry in fat and 1.2 K for proton resonance frequency shift-based thermometry in muscle were observed. The second application relates to MR-guidance of high-intensity focused ultrasound-induced local drug delivery by means of thermo-sensitive liposomes labeled with a T(1) contrast agent (Gd-HPDO3A). When the measured temperature exceeded the phase transition temperature of the liposomes, T(1) was observed to decrease with a good temporal and spatial correlation due to the release of Gd-HPDO3A. The presented results demonstrate the feasibility of the proposed method for two important applications in MR-guided noninvasive therapy. It offers a high temporal resolution when compared with interleaved Look-Locker based T(1) mapping techniques and thus represents an interesting candidate for simultaneous real-time monitoring of T(1) and temperature changes.

Online correction of respiratory-induced field disturbances for continuous MR-thermometry in the breast.

MR-thermometry allows monitoring of the local temperature evolution during minimally invasive interventional therapies. However, for the particular case of MR-thermometry in the human breast, magnetic field variations induced by the respiratory cycle lead to phase fluctuations requiring a suitable correction strategy to prevent thermometry errors. For this purpose a look-up-table-based multibaseline approach as well as a model-based correction algorithm were applied to MR-thermometry to correct for the periodic magnetic field changes. The proposed correction method is compatible with a variety of sensors monitoring the current respiratory state. The ability to remove phase artefacts during MR-thermometry of the human breast was demonstrated experimentally in five healthy volunteers during 3 min of free-breathing using pencil-beam navigators for respiratory control. An increase of 170-530% in temperature precision was observed for the look-up-table-based approach, whereas a further improvement by 16-36% could be achieved by applying the extended model-based correction.

Motivational/solution-focused intervention improves HbA1c in adolescents with Type 1 diabetes: a pilot study.

AIMS: We piloted a motivational and solution-focused therapy group intervention to improve glycaemic control in young people 11-17 years with poorly controlled Type 1 diabetes (mean annual HbA1c >8.5%). METHODS: Seventy-seven subjects agreed to be assessed for a pilot non-randomized controlled trial. Subjects completed psychological questionnaires and were given feedback designed to encourage entry into the intervention. Twenty-one young people opted to enter the intervention groups (cases). Two intervention groups consisting of five to six subjects were conducted in each age band 10-13 years and 14-17 years. Twenty of those who did not opt to join the groups were randomly selected to act as controls. Cases and controls were well matched for age, HbA1c, duration of diabetes and socio-economic status. RESULTS: The intervention produced a significant improvement of 1.5% in HbA1c in cases (P<0.05) at 4-6 months post intervention compared with no change in controls. This improvement was partly maintained at 7-12 months post intervention. CONCLUSIONS: These pilot data suggest that a motivational/solution-focused group intervention is promising in improving HbA1c in adolescents and should be investigated further in a randomized controlled trial.

Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway.

A Caenorhabditis elegans ORF encoding the presumptive condensing enzyme activity of a fatty acid elongase has been characterized functionally by heterologous expression in yeast. This ORF (F56H11. 4) shows low similarity to Saccharomyces cerevisiae genes involved in fatty acid elongation. The substrate specificity of the C. elegans enzyme indicated a preference for Delta(6)-desaturated C18 polyunsaturated fatty acids. Coexpression of this activity with fatty acid desaturases required for the synthesis of C20 polyunsaturated fatty acids resulted in the accumulation of arachidonic acid from linoleic acid and eicosapentaenoic acid from alpha-linolenic acid. These results demonstrate the reconstitution of the n-3 and n-6 polyunsaturated fatty acid biosynthetic pathways. The C. elegans ORF is likely to interact with endogenous components of a yeast elongation system, with the heterologous nematode condensing enzyme F56H11.4 causing a redirection of enzymatic activity toward polyunsaturated C18 fatty acid substrates.

Short-term oral toxicity study of FAVOR PAC in rats.

A short-term rat feeding study was conducted to evaluate the oral toxicity of FAVOR PAC (CAS Registry No. 9003-04-7), one member of a family of cross-linked sodium polyacrylate polymers developed by Stockhausen GmbH & Co KG (Krefeld, Germany). FAVOR polymers are classified as superabsorbent polymers because of their ability to absorb and retain large volumes of fluid. In this short-term study, three groups of 10 male and 10 female Sprague-Dawley rats were administered 0 (control), 1, or 5% FAVOR PAC in the diet daily for up to 32 days. No significant changes in clinical signs, body weight and food consumption, functional observation battery results, ophthalmoscopy, hematology and clinical chemistries, or absolute and relative organ weights were observed. Significant differences between treated and control animals were limited to increases in water consumption and modifications in urinary ionic excretion. Both findings were likely the result of the relatively high concentration of sodium in the test article, and thus consistent with adaptive physiologic changes, not overt toxicity. In conclusion, levels of up to 5% FAVOR PAC in the diet produced no treatment-related toxicity in rats under the conditions of this short-term test (i.e., a NOAEL of 5% FAVOR PAC in the diet was identified).

Mutagenicity studies of FAVOR PAC.

A series of in vitro and in vivo assays have been conducted using FAVOR PAC (CAS Registry No. 9003-04-7), a cross-linked sodium polyacrylate polymer, to test its ability to induce mutations. FAVOR PAC is a member of the FAVOR family of superabsorbent polymers (SAPs) developed by Stockhausen GmbH & Co KG (Krefeld, Germany). These SAPs are known for their ability to retain large volumes of fluid, even against pressure. The genotoxic potential of FAVOR PAC and its extracts was examined in the following five standard mutagenicity assays: the Salmonella typhimurium and Escherichia coli reverse mutation assay, the mouse lymphoma fluctuation assay, the mouse lymphoma forward mutation assay, the in vivo mouse micronucleus assay, and an in vitro rat DNA synthesis assay. Based on the results of these assays, it was concluded that FAVOR PAC was clearly not genotoxic under any of the conditions of the mutagenicity assays performed.

Disposition of radiolabeled FAVOR PAC in rats.

FAVOR is the name for a family of superabsorbent cross-linked sodium polyacrylate polymers developed by Stockhausen GmbH & Co KG (Krefeld, Germany) that are known for their ability to absorb and retain large volumes of fluid. The absorption, distribution, rates and routes of excretion of radiolabeled FAVOR PAC (CAS Registry No. 9003-04-7; [14C]FAVOR PAC), one member of the FAVOR family, were evaluated following a single oral administration of the compound. Male Sprague-Dawley rats were administered single doses of 26 to 39 mg/kg [14C]FAVOR PAC by gavage. Approximately 98.8% (normalized mean) of the total administered dose was excreted in the feces within 5 days, and the majority ( approximately 88%) was excreted within the first 24 h. Urinary excretion accounted for 0.69% (normalized mean) of the total administered dose. Recovery of radioactivity in the organs, tissues, and carcass was generally less than 0.5% of the dose administered. Levels of total radioactivity in whole blood ranged from 0.75 to 1.20 microg equiv/g. Biliary elimination of total radioactivity accounted for less than 0.1% of the dose administered. The results indicate that FAVOR PAC is poorly absorbed and rapidly eliminated in feces following oral administration.

The localization and expression of the class II starch synthases of wheat.

The starch granules of hexaploid wheat (Triticum aestivum) contain a group of three proteins known as SGP-1 (starch granule protein-1) proteins, which have apparent molecular masses of 100, 108, and 115 kD. The nature and role of these proteins has not been defined previously. We demonstrate that these polypeptides are starch synthases that are present in both the starch granule and the soluble fraction at the early stages of wheat endosperm development, but that are exclusively granule bound at mid and late endosperm development. A partial cDNA clone encoding a fragment of the 100-kD protein was obtained by screening a wheat endosperm cDNA expression library using monoclonal antibodies. Three classes of cDNA were subsequently isolated from a wheat endosperm cDNA library by nucleic acid hybridization and were shown to encode the 100-, 108-, and 115-kD proteins. The cDNA sequences are highly homologous to class II starch synthases and have the highest homology with the maize SSIIa (starch synthase IIa) gene. mRNA for the SGP-1 proteins was detected in the leaf, pre-anthesis florets, and endosperm of wheat and is highly expressed in the leaf and in the grain during the early to mid stages of development. We discuss the roles of the SGP-1 proteins in starch biosynthesis in wheat.