The red hearing: swollen ear in a patient with ulcerative colitis

Relapsing polychondritis is a rare connective tissue disease of unknown etiology characterized by recurrent inflammation, degeneration and deformity of auricular cartilage. The autoimmune inflammation may also affect cartilage at other sites including nose, larynx, trachea and bronchi. Here, we present a case of relapsing polychondritis in a patient with ulcerative colitis. We also review the presentation, diagnosis and management of this condition

An unusual cause of hypoglycemia in a middle-aged female after bariatric surgery

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a disorder characterized by postprandial hypoglycemia and islet cell hypertrophy. It is an uncommon complication of weight-loss surgery. However, with the rising incidence of gastric bypass surgeries, it is important to be able to recognize the clinical picture of NIPHS and not to incorrectly ascribe the symptoms to late dumping syndrome

HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants

Otitis media with effusion (OME) is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF) mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1a gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006) and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF–mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF–mediated pathways, and we conclude that targeting molecules in HIF–VEGF signaling pathways has therapeutic potential in the treatment of chronic OM

A Mouse Model for Osseous Heteroplasia

GNAS/Gnas encodes Gsa that is mainly biallelically expressed but shows imprinted expression in some tissues. In Albright Hereditary Osteodystrophy (AHO) heterozygous loss of function mutations of GNAS can result in ectopic ossification that tends to be superficial and attributable to haploinsufficiency of biallelically expressed Gsa. Oed-Sml is a point missense mutation in exon 6 of the orthologous mouse locus Gnas. We report here both the late onset ossification and occurrence of benign cutaneous fibroepithelial polyps in Oed-Sml. These phenotypes are seen on both maternal and paternal inheritance of the mutant allele and are therefore due to an effect on biallelically expressed Gsa. The ossification is confined to subcutaneous tissues and so resembles the ossification observed with AHO. Our mouse model is the first with both subcutaneous ossification and fibroepithelial polyps related to Gsa deficiency. It is also the first mouse model described with a clinically relevant phenotype associated with a point mutation in Gsa and may be useful in investigations of the mechanisms of heterotopic bone formation. Together with earlier results, our findings indicate that Gsa signalling pathways play a vital role in repressing ectopic bone formation

Effectiveness of Clinical Decision Support for Reducing Unnecessary Hypercoagulability Evaluations in a Large Community Hospital

Background: Venous Thromboembolism (VTE) is a potentially life-threatening disorder and in some cases, is related to underlying hypercoagulability which may be congenital or acquired. Guidelines suggest performing extensive work -up for hypercoagulability only in select patients: those with close family history of VTE at young age ( \u3c 45), young age at first VTE ( Methods: Clinical decision support in the form of a new cascading order set was developed on the hospital’s Electronic Medical Records (EMR) for VTE admissions. A section of the order set provided evidenced-based guidance for ordering hypercoagulable work-up in real time by providing relevant prompts (age, provoked/unprovoked, active thrombus, anticoagulation) at the point of order entry. Tests were also grouped based on the prompts so that gene tests alone or gene tests and functional tests were auto-selected based on the response to the prompts. For measuring its effectiveness, hypercoagulable workups were defined as appropriate when ordered in patients who are \u3c 45 years of age with unprovoked thrombus. In addition, functional tests had to be performed only in patients without active thrombi or anticoagulants. Tests that did not meet these criteria were deemed inappropriate. The order set was rolled out in April 2015, after extensive education of health care providers and the effects of intervention on appropriate test ordering were subsequently measured until May 2017. The 12 month period preceding the roll-out was used as the baseline year (pre-intervention). Our primary outcome measure was the average monthly number of patients with inappropriate work-ups and average cost savings per month was the secondary measure, using current costs of laboratory tests. All data was collected from reports generated on the Hospital EMR. Results: Over the 2 years after the addition of the clinical decision support intervention, there was a reduction of the average number of patients with inappropriate hypercoagulable state work-ups from 33 per month ( pre-intervention) to 14 per month (post intervention) – a 57% reduction. Cost savings realized per month from the intervention was $4,500 per month on average (pre-intervention:$9,050.73, post-intervention $4,569.98; P – 0.0004) and totaled about$117,000 over 26 months post intervention. Conclusions: Clinical decision support interventions may result in a sustained decrease in unnecessary hypercoagulable workups

Effectiveness of Clinical Decision Support for Hypercoagulable Evaluations in One Hospital

Introduction: Venous Thromboembolism (VTE) is a potentially life-threatening disorder that may be provoked by venous stasis, endothelial injury or hypercoagulable states. Workups for hypercoagulable states are frequently undertaken, but tests performed are often either not indicated (if performed in older patients, provoked VTE) or uninterpretable ( if functional tests are ordered while patient anticoagulated or with active thrombus). Clinical decision support at point of order entry has the potential to prevent this unnecessary testing. As part of a larger QI project to improve care of VTE patients, we studied the impact of clinical decision support embedded in order sets, measuring the rates of appropriate hypercoagulable evaluations as a primary outcome. Intervention: This study was undertaken from February 2013 - May 2015, and the effects of intervention were subsequently measured until May 2017. Hypercoagulable workups were defined as appropriate when ordered in patients who are \u3c 45 years of age with unprovoked thrombus for all tests (gene and functional tests); and patients without active thrombi or anticoagulants for functional tests. A new order set was developed on the hospital health information system for VTE admissions. The order set provided evidenced-based guidance for ordering work-up. The order set was rolled out in April 2015, after extensive education of health care providers. Outcome: Over the 2 years after the addition of the clinical decision support intervention, there was a reduction of the total number of hypercoagulable state work-ups from 21% pre-intervention to 15.7% post intervention, the average number of inappropriate tests reduced from 33 to 14 per month - a 57% reduction. Cost savings realized per month from the intervention was approximately $4,500 (pre-intervention:$9,050.73, post-intervention $4,569.98; P - 0.0004) and totaled about$117,000 over 26 months post intervention. Conclusion: Clinical decision support interventions may result in a sustained decrease in unnecessary hypercoagulable workups