Sensory information may be represented in the brain by stereotyped mapping of axonal inputs or by patterning that varies between individuals. In olfaction, a stereotyped map is evident in the first sensory processing centre, the olfactory bulb (OB), where different odours elicit activity in unique combinatorial patterns of spatially invariant glomeruli. Activation of each glomerulus is relayed to higher cortical processing centres by a set of ∼20-50 'homotypic' mitral and tufted (MT) neurons. In the cortex, target neurons integrate information from multiple glomeruli to detect distinct features of chemically diverse odours. How this is accomplished remains unclear, perhaps because the cortical mapping of glomerular information by individual MT neurons has not been described. Here we use new viral tracing and three-dimensional brain reconstruction methods to compare the cortical projections of defined sets of MT neurons. We show that the gross-scale organization of the OB is preserved in the patterns of axonal projections to one processing centre yet reordered in another, suggesting that distinct coding strategies may operate in different targets. However, at the level of individual neurons neither glomerular order nor stereotypy is preserved in either region. Rather, homotypic MT neurons from the same glomerulus innervate broad regions that differ between individuals. Strikingly, even in the same animal, MT neurons exhibit extensive diversity in wiring; axons of homotypic MT pairs diverge from each other, emit primary branches at distinct locations and 70-90% of branches of homotypic and heterotypic pairs are non-overlapping. This pronounced reorganization of sensory maps in the cortex offers an anatomic substrate for expanded combinatorial integration of information from spatially distinct glomeruli and predicts an unanticipated role for diversification of otherwise similar output neurons.
Signet-ring cell carcinoma (SRCC) is an adenocarcinoma characterized by mucin-producing cells and most commonly arises in the stomach. Colonic SRCC can share features of colitis, including long segments of concentric bowel wall thickening and ulcerated mucosa with regions of sparing. We describe a rare case of metastatic gastric SRCC mimicking Crohn’s disease. Our patient underwent 2 colonoscopies, and biopsies revealed chronic active inflammation with no evidence of malignancy. The diagnosis of SRCC was only made after colectomy was performed for recurrent bowel obstruction.
INTRODUCTION: Vedolizumab is an anti-integrin therapy for IBD. It is a monoclonal antibody that selectively inhibits the interaction between the MAdCAM-1 receptor and α4β7 integrin in the gut. Vedolizumab, in comparison to other biologics, has a smaller pool of literature designating it's safety profile, specifically in the elderly (age >65 years of age) population of IBD patients. The GEMINI post-hoc trials have indicated an acceptable rate of infections, adverse reactions leading to hospitalization, and rate of malignancy in patients older than 55 years of age. The elderly subset of patients, designated as those 60-65 years of age or older by prior literature, is a growing population in need of effective and safe treatment of their IBD. METHODS: We searched the Epic database for Lahey patients with a diagnosis of inflammatory bowel disease, searching for patients who had been prescribed vedolizumab for this diagnosis. Of the compiled list of patients collected with these criteria, we searched the patient charts for the occurrence of flares, infections, development of malignancy, and death. Reasons for exclusion from the study include discontinuation of vedolizumab before completion of induction dosing, not being on vedolizumab, and lack of gastroenterology follow-up at Lahey Medical Center by a Lahey gastroenterologist. RESULTS: Of a total of 86 patients with IBD, ages ranging from 23-81 years of age, there was no significant difference found in the time to flare, time to remission from flare, incidence of infections, arthralgias, or malignancy in patients with IBD >65 after starting vedolizumab. Non-melanomatous skin cancer was the most common malignancy diagnosed after starting vedolizumab in both groups. CONCLUSION: Our data indicated no statistical difference between the adverse reactions leading to hospitalization, time to flare, and malignancy between the elderly and non-elderly IBD patients undergoing treatment with vedolizumab. However, our current data is primarily limited by small sample size and unequal study arm size. Also, our sample is primarily Caucasian, limiting our data's application to non-white IBD patient populations. We are currently working to combine our data with that of other hospital populations to overcome this limitation.
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