No commercial re-use. See rights and permissions. Published by BMJ.We report the case of a 64-year-old pseudophakic patient in a rural area who chronically suffered from headache with eye pain and was on analgesics for pain relief but never turned up to an ophthalmologist. There was lack of awareness to visit an ophthalmologist for headache as he thought that after undergoing cataract surgery, the role of ophthalmologist was limited. His approach to our centre was only after intense headache with sudden loss of vision. He had actually developed secondary glaucoma due to pupillary block angle closure as a late complication following yttrium aluminium garnet capsulotomy. After medical and surgical management, he regained his complete vision with total relief from headache. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Recent years have seen an increase in use of mepolizumab and other biological therapies for the treatment of severe eosinophilic asthma. A few cases of paradoxical responses to mepolizumab therapy have now been reported and are hypothesised as being a response to immune complex formation. We present a case of mepolizumab-induced alopecia in a patient with paradoxical adverse response to mepolizumab given for severe eosinophilic asthma. We postulate this could be secondary to autoimmune mechanisms and that it could help herald poor response to treatment, thereby facilitating early identification of patients having paradoxical responses. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.We report a case of 'occult' bilateral optic nerve aplasia (ONA) where pituitary dysfunction was discovered subsequently. The initial ultrasonography had missed ONA in a child with bilateral microcornea, small non-dilating pupils and roving eye movements. Due to presence of relevant clinical signs in this case, ONA was re-evaluated with MRI, and was subsequently discovered to be associated with life-endangering hypopituitarism. This case raises the possible underestimation of ONA, and hence also the risk of missing life-threatening endocrine disorders. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.A 56-year-old man undergoing immunotherapy treatment for metastatic melanoma presented with sudden onset testicular pain radiating into his abdomen. On examination, the abdomen was generally tender with associated guarding. Imaging revealed a perforation of the small bowel at the site of a metastatic lesion. Histology revealed that this process was non-inflammatory in nature. A diagnosis of small bowel perforation secondary to immunotherapy driven rapid tumour regression was made. The patient was treated with a small bowel resection plus anastomosis and made a full recovery. This case highlights the rare potential side effect of immunotherapy in causing non-inflammatory bowel perforations secondary to rapid tumour regression. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.The present manuscript reports two extremely rare cases of coexisting emphysematous gastritis with gastric mucormycosis. The cases were managed successfully, considering the high mortality associated with both conditions independently. The aim of the manuscript is to elucidate the importance of prompt diagnosis, early surgical intervention for source control and concomitant application of antifungal therapy for a favourable outcome. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease. We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients. Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound. Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p less then 0.01). https://www.selleckchem.com/products/AC-220.html Plasma levels of autoantibodies against a singular GRP78 peptide segment, amino acids 246-260 (anti-GRP78aa 246-260), were even more highly correlated with cIMT, especially among males with greater than or equal to moderate COPD (r s = 0.62, p = 0.001). Anti-GRP78aa 246-260 concentrations were independent of CRP, IL-6, and TNF-α levels. GRP78 autoantigen expression was upregulated among human aortic endothelial cells (HAECs) stressed by incubation with tunicamycin (an unfolded protein response inducer) or exposure to culture media flow disturbances. Autoantibodies against GRP78aa 246-260, isolated from patient plasma by immunoprecipitation, induced HAEC production of proatherosclerotic mediators, including IL-8. In conclusion, anti-GRP78 autoantibodies are highly associated with carotid atherosclerosis in COPD patients and exert atherogenic effects on HAECs. These data implicate Ag-specific autoimmunity in the pathogenesis of atherosclerosis among COPD patients and raise possibilities that directed autoantibody reduction might ameliorate vascular disease in this high-risk population. Copyright © 2020 The Authors.TLR7 and TLR8 are pattern recognition receptors that reside in the endosome and are activated by ssRNA molecules. TLR7 and TLR8 are normally part of the antiviral defense response, but they have also been implicated as drivers of autoimmune diseases such as lupus. The receptors have slightly different ligand-binding specificities and cellular expression patterns that suggest they have nonredundant specialized roles. How the roles of TLR7 and TLR8 differ may be determined by which cell types express each TLR and how the cells respond to activation of each receptor. To provide a better understanding of the effects of TLR7/8 activation, we have characterized changes induced by TLR-specific agonists in different human immune cell types and defined which responses are a direct consequence of TLR7 or TLR8 activation and which are secondary responses driven by type I IFN or cytokines produced subsequent to the primary response. Using cell sorting, gene expression analysis, and intracellular cytokine staining, we have found that the IFN regulatory factor (IRF) and NF-κB pathways are differentially activated downstream of the TLRs in various cell types.