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.

Allergy immunotherapies for allergic rhinitis: systematic review and assessment of evolving quality.

Summary: Background. Heterogeneity in the design and quality of trials evaluating allergy immunotherapies (AITs) limits their comparability, making it difficult for physicians, patients, and payers to select the best treatment option. Methods. This systematic review evaluated the quality of randomised controlled trials (RCTs) of registered grass AITs using the National Institute of Health and Care Excellence checklist. Results. 17 of 44 unique RCTs (38.6%) (sample size range: 18-1,501 subjects) were subcutaneous grass immunotherapy trials and 27 (61.4%) were sublingual grass immunotherapy trials (Allergovit, 5 trials; Alutard, 8; Grazax, 13; Oralair, 6; Staloral, 8; Pollinex, 2; Phostal and Purethal, 1 each). Three trials (6.8%; all Grazax) fulfilled every quality criterion. Quality assessments revealed inconsistencies in study quality and reporting. Study quality trended towards improvement over time, particularly after 2009. Conclusions. When as-sessing grass AIT, it is important to focus not only on endpoints but also on the quality of evidence.

Diurnal profile of interstitial glucose following dexamethasone prophylaxis for chemotherapy treatment of gynaecological cancer.

AIMS: Hyperglycaemia, a side-effect of acute glucocorticoid exposure, is associated with poor outcome in those undergoing chemotherapy. The incidence, risk factors and diurnal profile of glucocorticoid-induced glucose dysregulation in the context of chemotherapy treatment remain incompletely understood. METHODS: Blinded continuous interstitial glucose monitoring was performed on 16 women without diabetes for 24 h prior to and 5 days following carboplatin/paclitaxel chemotherapy combined with dexamethasone treatment for gynaecological cancer. At the end of the treatment period, glucose data were analysed and integrated with baseline metabolic and anthropomorphic variables. RESULTS: 15/16 (94%) women exhibited elevated glucose levels (> 11.1 mmol/l). Peak glucose levels were highest on the day of treatment (median 14.45 mmol/l, range 10.2-22.2 mmol/l) and total time spent with an elevated interstitial glucose level was highly variable (median 3.6 h, range 0.0-55.1 h). Peak interstitial glucose levels occurred predominantly, but not exclusively, in the afternoon (13.00-15.00) and evening (19.00-22.00); however elevated levels were noted throughout the 24-h period. Baseline HbA1c was independently associated with severity and duration of elevated glucose levels in a regression adjusted for baseline BMI. CONCLUSIONS: These data report for the first time that high glucose levels are encountered by nearly all women following this regimen, the severity and duration of which are independently associated with HbA1c . Further work is required to determine if controlling glucose levels during treatment influences outcome.

A quantitative assessment of the number of disease foci in papillary thyroid cancer.

AIM: Multifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable. This study aimed to examine the association between increasing number of foci and risk of recurrence following treatment. METHODS: 577 patients with PTC were identified with median follow-up of 61 months. Number of foci were taken from pathology reports. Log-rank test was used to assess significance. Multivariate analysis was performed and Hazard Ratios were calculated. RESULTS: Of 577 patients, 206(35%) had multifocal disease and 36(6%) recurred. 133(23%), 89(15%) and 61(11%) had 3+, 4+ or 5+ foci respectively. The 5-year RFS stratified by number of foci was 95%v93% for 2+foci (p = 0.616), 95%v96% for 3+foci (p = 0.198) and 89%v96% for 4+foci (p = 0.022). The presence of 4 foci was associated with an over 2-fold risk of recurrence (HR 2.296, 95% CI 1.106-4.765, p = 0.026) although this was not independent of TNM staging. Of the 206 multifocal patients, 31(5%) had 4+foci as their sole risk factor for treatment intensification. CONCLUSION: Although multifocality per se does not confer worse outcome in PTC, finding 4+foci is associated with worse outcome and could therefore be appropriate as a cut-off for treatment intensification. In our cohort, 5% of patients had 4+foci as a sole indication for treatment intensification, suggesting that such a cut off could impact clinical management.

Diffractive multifocal intraocular lens implants for unilateral cataracts in prepresbyopic patients.

Multifocal intraocular lenses allow pseudophakic patients to obtain good near and distance visual acuities without an additional near correction. We report our experiences in implanting diffractive multifocal intraocular lenses in prepresbyopic patients with acquired unilateral cataracts and assess their postoperative visual acuities and stereoscopic vision. Accommodative function in patients following cataract surgery is discussed.

Proplast implant in Tenon's capsule after excision of the eye.

Hitherto implants used after enucleation have generally been extruded because of infection or tissue rejection. Proplast, an inert alloplastic material prepared from a combination of Teflon fluorocarbon polymer and vitreous carbon fibres, is a grey felt-like material which, when wholly implanted, is invaded by fibrous tissue and not rejected. Hemispherical implants of Proplast have been used in sixteen cases, no rejection has occurred to date (18 months), and movement of the implant has been good. At operation, the obliques are sutured posterior to the implant so as to hold it forwards and increase movement. The rectus muscles are sutured anterior to the implant in cruciate fashion. Tenon's capsule and the conjunctiva are closed separately.

Recurrent anaemia due to ischaemic colonic ulceration caused by cholesterol embolism.

We describe an elderly patient with generalized atherosclerosis who presented with recurrent iron-deficiency anaemia. He underwent right hemicolectomy which revealed ischaemic colonic ulceration caused by cholesterol embolism. Surgery appeared to be curative. Cholesterol embolism should be considered as a possible cause of unexplained gastrointestinal blood loss in the elderly.

Diagnosis of intestinal duplication by 99Tcm-pertechnetate scanning.

A case is described of a 19-month-old boy who presented with melaena. Intestinal duplication was diagnosed by 99Tcm-pertechnetate scanning and was confirmed at operation 2 years later, when the child was admitted with intestinal perforation. The technique is a reliable, non-invasive method for diagnosing ectopic gastric mucosa and is recommended in all cases of unexplained rectal bleeding in children.

Anti-HPA-1a-mediated platelet phagocytosis by monocytes in vitro and its inhibition by Fc gamma receptor (FcgammaR) reactive reagents.

The study was undertaken to delineate mechanisms of platelet destruction by phagocytosis during fetal/neonatal alloimmune thrombocytopenia (FAIT/NAIT) because of maternal antibodies against human platelet antigen 1a (HPA-1a). By employing a platelet phagocytosis assay based on the ORPEGEN flow cytometric bacterial phagocytosis test, we measured monocyte ingestion of platelets mediated by anti-HPA-1a antibodies. Moreover, we tested, as potential therapeutic agents, FcgammaR reactive reagents, for their inhibition of this process. Four of six anti-HPA-1a sera tested mediated phagocytosis of HPA-1a-positive platelets in a concentration-dependent manner. Monocyte ingestion of platelets was almost completely inhibited by cytochalasin D. No anti-HPA-1a-mediated phagocytosis was observed with anti-HPA-1a-negative platelets. The humanised anti-FcgammaRI monoclonal antibody H22 at concentrations 1-100 microg/ml, completely inhibited anti-HPA-1a-mediated phagocytosis as did similar concentrations of ivIg. By contrast, a mouse monoclonal anti-FcgammaRII (IV.3, Fab) at 10 microg/ml caused little or no suppression of platelet phagocytosis mediated by two anti-HPA-1 sera. Furthermore, the addition of anti-FcgammaRII (10 microg/ml) to sub-optimal concentrations of H22 did not significantly increase the inhibitory effect of the latter compound. Monomeric IgG (0.1-10 microg/ml) failed to suppress anti-HPA-1 mediated platelet ingestion by the phagocytes, as did anti-FcgammaRIII. To our knowledge this is a rare example of an assay that measures platelet phagocytosis in vitro. The results suggest that FcgammaRI plays a major role in anti-HPA-1a-mediated platelet phagocytosis by monocytes while FcgammaRIIa, is of little or minor importance only. Moreover, the findings indicate the use of H22 as an alternative to interavenous Ig (ivIg) in the management of FAIT/NAIT.