Women with polycystic ovary syndrome (PCOS) are at increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In this study, we attempted to list the proteomic biomarkers of PCOS and T2DM that have been published in the literature so far. We identified eight common biomarkers that were differentially expressed in both women with PCOS and T2DM when compared with healthy controls. These include pyruvate kinase M1/M2, apolipoprotein A-I, albumin, peroxiredoxin 2, annexin A2, a-1-B-glycoprotein, flotillin-1 and haptoglobin. These biomarkers could help improve our understanding of the links between PCOS and T2DM and could be potentially used to identify subgroups of women with PCOS at increased risk of T2DM. More studies are required to further evaluate the role these biomarkers play in women with PCOS and T2DM.European Journal of Endocrinology 168 R33-R43

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC.

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Background/Aims Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive condition first described in 2014 which is characterised by vasculitis, systemic inflammation, immunodeficiency and cytopenias. The vasculitis is difficult to differentiate from polyarteritis nodosa and typically presents with recurrent strokes. It can also affect the skin and present with livedo racemosa. Clinical presentation varies widely; from vasculitic manifestations which tend to present later in life to severe haematological abnormalities such as bone marrow failure which tend to present earlier in life. Treatment with TNF inhibitors reduces the risk of additional strokes and controls inflammation in the presence of vasculitis but is not very effective against bone marrow failure. Methods We present the case of a 44-year-old gentleman who was being investigated for possible vasculitis by the rheumatology team in view of a history of Raynaud’s, 20-year history of recurrent leg ulcers and a previous pontine infarct. He presented acutely to the emergency department with numbness below the midthoracic level, weakness of his lower limbs and hands and urinary retention. His symptoms had progressed over a period of a few hours. On examination power was 4/5 on the MRC power scale for shoulder abduction and elbow flexion, 2/5 for elbow extension, 3/5 for wrist extension and 1/5 for finger extension. Power was 1/5 on his lower limbs. Sensation to pain was reduced with a T6 sensory level. Proprioception and vibration sense were intact. Upper limb reflexes were brisk. Knee jerks and left ankle jerk were difficult to elicit. Plantars were downgoing. Cranial nerves were normal. Results Bloods showed a white cell count of 6.7x109/l, haemoglobin of 96g/l (microcytic), platelets of 243x109/l, creatinine 119μmol/l (baseline 85μmol/l) and CRP of 42.9mg/l. Vitamin B12 was 200ng/l and folate levels were 2.2μg/L. ANA, ANCA, cryoglobulins and hepatitis serology were negative. MRI brain showed a 4mm area of hyper-density in the left pons. MRI whole spine was unremarkable. CSF showed normal protein, white cell count and glucose level. The patient was transferred to a tertiary neurology centre and a diagnosis of anterior spinal cord infarction was made. A nerve biopsy was performed which showed evidence of vasculitis and he was pulsed with methylprednisolone and commenced on high dose oral steroids. Genetic testing showed a pathogenic mutation in the adenosine deaminase 2 gene. He is currently awaiting to commence treatment with TNF inhibitors. Conclusion We conclude that DADA2 is an important differential in a young patient with suspected vasculitis especially in the presence of infarction. Identification of DADA2 allows initiation of treatment with TNF inhibitors which reduces the risk of additional strokes. Disclosure M. Xenophontos: None. J. Gan: None. A.C. Seneviratne: None.