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There is limited data on prevalence of PD-L1 expression in papillary thyroid cancer (PTC). Anti- PD-L1 therapy is now being trialled for head and neck cancers including thyroid cancer. Whether presence of PD-L1 staining in PTC might result in a better response to anti-PD-L1 therapy is uncertain. We evaluated the frequency of tumoral PD-L1 expression using standard antibody (SP263) and clinicopathologic factors including mutation status - BRAF, NRAS, KRAS using OncoFocus Mass Array System in an Australian PTC cohort with low or high risk of recurrence /treatment response as per 2015 ATA guidelines. The cohort had 128 patients; 66% were females; 40% had both multifocal and bilateral PTC; 47% had low recurrence risk, of whom 92% had excellent treatment response; 34% had high recurrence risk, of whom 37% had structural incomplete treatment response. There was nil (0%) PD-L1 staining in 59%, 1% staining in 20%, 5-10% staining in 11%, >10% staining in rest of the cohort; 30%, 40% and 70% staining was seen in 2% each. PD-L1 in immune cells was positive in 62%. There was no significant association between PD-L1 tumour status and age, gender, size of tumour, multifocality, bilaterality, both multifocality and bilaterality, lymphovascular invasion, perineural invasion, extrathyroidal extension (ETE), histological variants, risk stratification, treatment response, metastases or mutation status. Among PD-L1 negative vs positive patients, BRAFV600E was present in 64.9% vs 67.5%, NRAS in 8.8% vs 0% and nil mutation in 26 % vs 33 % p=0.15. The staining thresholds were chosen according to existing literature. When analysed according to the percentage of PD-L1 staining (0%, 1-10% and >=10% thresholds), there was no significant association between PD-L1 staining category and other features, except for ETE (35% vs 65% vs 27%; p=0.007), a relationship that remained significant in a multivariable-adjusted model (OR 9.9, p=0.04). PD-L1 staining thresholds of =5% were significantly associated with the size of tumour (24.7±15.4 vs 33.3±21.8; p=0.02) and histological variants (57 % vs 61% for classic variants and 27% vs 11% for follicular variants, p=0.03). This is the first study to our knowledge that analysed PD-L1 staining based on the risk stratification categories. The majority of PTC showed negative or low staining intensity for PD-L1 expression. There was no significant association between PD-L1 staining, clinicopathologic characteristics and mutation status of the PTC. Relatively less ETE was seen in the group that showed >=10% and also >=5% PD-L1 staining as compared to the group that showed 1%

Angelman syndrome (AS) is a neurodevelopmental disorder categorized by severe disability in intellectual functions and affected by the loss of function of maternally inherited UBE3A gene. Mice deficient for the maternal Ube3a recapitulates many distinguishing behavioral features of the AS and is used as a typical model system to understand the disease pathogenic mechanism. Here, we first show a significant increase in HDAC1 and HDAC2 activities in AS mice brain from as early as embryonic day 16(E16). In depth study further reveals that the deficiency of Ube3a leads to transcriptional up-regulation of both HDAC1 and HDAC2. Restoration of HDAC1 and HDAC2 activities (as evident from the increased acetylation of histones H3 and H4) using simvastatin significantly improves the cognitive deficit and social interaction behavior in AS mice. Simvastatin treatment also restores the reduced level of BDNF in AS mice brain. Finally, we demonstrate that the treatment of simvastatin to primary cortical neuronal culture prepared from AS mice embryo also rescues altered acetylation of histones H3 and H4 and the level of BDNF. These results suggest that simvastatin could be a promising drug for the treatment of AS.

PTC and melanoma are known to harbour common mutations, but this has not been extensively investigated. Targeted therapies for BRAF and PD-L1 have been used for melanoma and there are ongoing clinical trials for use of PD-L1 inhibitors in PTC but its utility is uncertain. Additionally, many of these patients have multiple cancers, so, whether they have a tumour predisposition syndrome is also unclear. Both germline and somatic mutations in BRCA1-associated protein 1 (BAP1) are associated with a wide spectrum of tumours. We hypothesized that a common genetic link may be present in our cohort of patients who have both PTC and melanoma. The aim of this study was to elucidate molecular genetics, specifically BRAF, NRAS, KRAS, KIT using OncoFocus Mass Array System as well as expression of PD-L1 and BAP1, using a standard antibody (SP263) and C-4 respectively, in an Australian cohort with concurrent PTC and melanoma. In our cohort of 21 patients (43% females, all Caucasian), melanoma was diagnosed about 8 years prior to PTC (50.3 ± 18.3 vs. 58.6 ± 12.8 years). The most common mutation was BRAFV600E seen in 88% of PTC, followed by NRAS mutation in 12% of PTC. Majority of the PTC (68%) stained negative for PD-L1. There was no significant association between PD-L1 tumour status and clinicopathologic outcomes. Interestingly, majority of multifocal, bilateral and both bilateral and multifocal PTC were PD-L1 negative (85%,69% and 69% respectively, P25%, a much higher degree of staining compared to PTC group. Among 7 patients where data were available for both tissues, concordant mutations were found in only 2 patients (both BRAFV600E). In addition, 11 of the 21 patients had at least one other cancer apart from PTC and melanoma. Nine of the 11 patients who had more than one cancer were BRAF positive. BAP1 staining was retained in the majority of PTCs and melanoma tissues, indicating no loss of BAP1 protein. PTC and melanoma both share molecular markers including BRAF, NRAS, PD-L1 as shown in our cohort. This is the largest study describing the mutation status of both PTC and melanoma. It is also the only study describing the PD-L1 and BAP1 expression in PTC and melanoma. BRAFV600E was the most common mutation. Majority of the PTC and melanoma stained negative for PD-L1. BAP1 expression was retained in both either PTC and melanoma tissues thus making presence of BAP1 tumour predisposition syndrome unlikely.

AIM To investigate if glycaemic profiles and outcomes of patients with diabetes admitted for cardiothoracic surgery or acute coronary syndrome improved after implementation of a structured glycaemia management guideline. METHODS This is a retrospective before-and-after comparative analysis of outcomes for all consecutive cardiothoracic and acute coronary syndrome patients with diabetes (N = 375), who were admitted at our tertiary-care university-affiliated hospital during the preguideline period (July-December, 2013) and the postguideline period (July-December, 2014). RESULTS A total of 55 cardiothoracic and 136 acute coronary syndrome patients were enrolled in the before period, and 36 cardiothoracic and 148 acute coronary syndrome patients were enrolled in the after period. In the cardiothoracic group, comparing the before vs after period, mean BGL improved (9 vs 8.4 mmol/L, P = .045), but there were no significant differences in the readmission rate (18% vs 14%; P = .6), number of hypoglycaemic episodes (1 vs 1, P = .5) or in-hospital mortality (0% vs 5.6%; P = .08). In the acute coronary syndrome group, there were no significant pre-post differences in the mean BGL (9.4 vs 10.2 mmol/L, P = .14), readmission rate (10% vs 11%; P = .8), number of hypoglycaemic episodes (1 vs 1, P = 1.0) or in-hospital mortality (5% vs 7%; P = .4). Endocrinology referrals increased significantly during the after period. CONCLUSIONS Implementation of a structured guideline for glycaemia management on inpatient wards marginally improved glycaemic profiles in the cardiothoracic group but not in the acute coronary syndrome group.

Objective: To report a case of a giant retroperitoneal teratoma involving the adrenal gland associated with persistent postoperative adrenal insufficiency likely due to the secretion of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from the teratoma.Methods: We describe the presenting signs and symptoms, investigations, and pathologic features leading to the diagnosis and treatment options.Results: A 29-year-old male was found to have a large retroperitoneal mass arising near the right kidney and adrenal, encasing the dual renal arteries and causing right urinary tract obstruction on computed tomography imaging. Resection of the mass required right nephrectomy and median sternotomy. Microscopy demonstrated a mature teratoma arising from the retroperitoneum. The right adrenal gland was compressed and trapped in the edge of the mass. His postoperative course was complicated by unexpected persistent hypocortisolism requiring cortisol replacement. Subsequent immunostaining was positive for CRH and ACTH, suggesting that the teratoma was secreting CRH and ACTH.Conclusion: This is the first reported case of teratoma associated with CRH and ACTH secretion leading to postoperative adrenal insufficiency. Although extremely rare, the possibility of a teratoma secreting hormones should be kept in mind and appropriate evaluation is recommended pre- and postoperatively.ACTH = adrenocorticotropic hormone; AFP = alphafetoprotein; CRH = corticotropin releasing hormone; CT = computed tomography; RR = reference range

Background Anemia and micronutrient deficiencies are common among Indian schoolchildren. However, past studies have narrowly focused on only a few micronutrients and have not carefully evaluated the association between sociodemographic factors and nutritional status of schoolchildren. Objective To assess the nutritional status of schioolchildren in Himalayan villages of India and to determine the relationships between their nutritional status, intestinal helminth infection, and sociodemographic characteristics. Methods A random sample of 499 children 6 to 10 years of age from 20 public primary schools was selected. Household sociodemographic data and morbidity data on children were collected through interviews with their caretakers. Height and weight were measured, and venous blood was drawn for assessment of hemoglobin, serum ferritin, soluble transferrin receptor, retinol, zinc, folic acid, vitamin B12, and C-reactive protein. Stool samples were analyzed for parasitic infections. Results Underweight, stunting, and wasting were present in 60.9%, 56.1%, and 12.2% of schoolchildren, respectively. Anemia, iron-deficiency anemia, and low serum concentrations of ferritin, zinc, retinol, folate, and vitamin B12 were found in 36.7%, 10.2%, 24.1%, 57.1%, 56.1%, 67.9%, and 17.4% of the children, respectively. One-fifth of the children had intestinal parasites. Being underweight was associated with lower household wealth ( p < .05). Helminth infection was associated with stunting, anemia, and low serum retinol ( p < .05). Living at higher altitude was associated with low serum levels of ferritin, retinol, and vitamin B12. There were no associations between any sociodemographic variables and serum zinc or folate. Conclusions Growth impairment and micronutrient deficiencies are prevalent among schoolchildren in Himalayan villages of India.