THU0601 REFRACTORY ACUTE CORONARY SYNDROME AND CARDIOGENIC SHOCK AS ATYPICAL ONSET OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

Background:Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an ANCA-associated vasculitis, characterized by eosinophilic infiltration in tissues, intravascular and extravascular granuloma formation. It is a rare disease, affecting between 0 and 4 per million population per year. The cardiac involvement occurs in 15-60% of EGPA patients (generally ANCA-negative); it is often insidious, underestimated and it has a poor prognosis. The disease usually shows a prodromal phase characterized by asthma and allergic manifestations.Objectives:We report the case of a young patient with acute coronary syndrome (ACS) complicated by cardiogenic shock as the first manifestation of EGPA.Methods:A 36 year old Indian male patient, with a previous history of asthma, rhinitis, Raynaud syndrome and allergy to ketoprofen, presented to the emergency department with a complaint of chest pain and dyspnea. Cardiac troponin was elevated and he was admitted to intensive care unit with a diagnosis of ACS. The patient conditions rapidly deteriorated due to acute cardiogenic shock and an urgent coronary angiogram was performed. An occlusion of the left main coronary artery was treated with angioplasty and two drug-eluting stents. Echocardiography showed severe left ventricular dysfunction requiring inotropic and intra-aortic balloon pump support. A mild dermatitis after salicylic acid administration resolved with intravenous hydrocortisone 1 g. The thrombophilia screening was negative, as well as cardiovascular risk factors. Over the next days, the clinical conditions rapidly improved with recovery of normal ventricular function on discharge. However, two weeks later he was readmitted with recurrent mandibular and chest pain. Troponin levels were elevated and fluctuated, suggesting recurrent ischemic events. Repeated ECG during angina crisis showed ischemic alterations in different coronary territories. The coronary angiogram detected coronary vasospasm of the circumflex artery, reversible after nitroglycerin (Figure 1). Nitroglycerin and calcium channel blockers were initiated, but did not resolve the vasospastic angina crisis, occurring daily. Laboratory tests revealed eosinophilia (4390 cells/mcl), increased C reactive protein (9.4 mg/l) and positive antinuclear antibodies (1:320). The other serological and immunological tests were negative, including MPO-ANCA and PR3-ANCA. An abdomen and chest CT scan was negative.Figure 1.Coronary angiogram showing coronary vasospasm in the left circumflex artery (panel A, yellow arrow), reversible after nytroglicerin infusion (panel B, yellow arrow)Results:The eosinophilia and the history of asthma rose the suspect of EGPA vasculitis. The patient was treated with intravenous methylprednisolone 250 mg once daily for 3 days, followed by oral prednisone 1 mg/kg/day, with rapid and complete resolution of the recurrent angina episodes. Intravenous cyclophosphamide 10 mg/kg was administered every 2 weeks for 2 times, then 12 mg/kg every 4 weeks. Oral corticosteroid was tapered, with the persistence of a complete remission of the symptoms, after 2 months of immunosuppressive therapy.Conclusion:Coronary involvement in EGPA can mimic atherosclerotic artery disease and can be life threatening, if not promptly recognized. An accurate medical history and complete serological and immunological tests are crucial to detect an atypical onset of EGPA, prompting early immunosuppressive therapy which is pivotal for the patient survival.References:[1]MR Hazebroek et al. Prevalence and Prognostic Relevance of Cardiac Involvement in ANCA-associated Vasculitis: Eosinophilic Granulomatosis With Polyangiitis and Granulomatosis With Polyangiitis. Int J Cardiol 2015, 199: 170-9.Disclosure of Interests:None declaredDOI: 10.1136/annrheumdis-2020-eular.648

A Cross-level Verification Methodology for Digital IPs Augmented with Embedded Timing Monitors

Smart systems implement the leading technology advances in the context of embedded devices. Current design methodologies are not suitable to deal with tightly interacting subsystems of different technological domains, namely analog, digital, discrete and power devices, MEMS and power sources. The interaction effects between the components and between the environment and the system must be modeled and simulated at system level to achieve high performance. Focusing on digital subsystem, additional design constraints have to be considered as a result of the integration of multi-domain subsystems in a single device. The main digital design challenges combined with those emerging from the heterogeneous nature of the whole system directly impact on performance, hence propagation delay, of the digital component. In this paper we propose a design approach to enhance the RTL model of a given digital component for the integration in smart systems, and a methodology to verify the added features at system-level. The design approach consists of ``augmenting'' the RTL model through the automatic insertion of delay sensors, which are capable of detecting and correcting timing failures. The verification methodology consists of an automatic flow of two steps. Firstly the augmented model is abstracted to system-level (i.e., SystemC TLM); secondly mutants, which are code mutations to emulate timing failures, are automatically injected into the abstracted model. Experimental results demonstrate the applicability of the proposed design and verification methodology and the effectiveness of the simulation performance

Do foot pad scores measure Turkey welfare

The main aim of the project was to assess the painfulness of different levels of foot pad dermatitis (FPD) in turkeys. Three different analgesics (butorphanol, carprofen and meloxicam) were used to assess their effect on behaviour. Video recordings were taken when the birds were treated with either saline or one of the analgesics in a crossover experiment, with the aim of investigating whether or not FPD is a painful condition. The results did not show significant pain in affected turkeys. Carprofen may have an effect on behavior, whereas butorphanol and meloxicam did not

Footpad dermatitis and pain assessment in turkey poults using analgesia and objective gait analysis

The relationships between litter moisture, footpad dermatitis (FPD) and pain in medium-heavy turkey strains was studied by gait analysis in two medium-heavy with and without analgesia (betamethasone or bupivacaine). The relationship between FPD and litter moisture was linear above a breakpoint of 49% litter moisture, and there were no differences between the two breeds in susceptibility to FPD. Gait analysis showed higher impulse, single support time, stride time and stance time in breed A compared to breed B. Significant interactions between breed, litter and analgesic for impulse, single support time and stride time were associated with higher means for breed A given saline injection on wet litter. Data from betamethasone analgesia in Experiments 1 and 3 were combined for analysis. Peak vertical force was higher in saline- compared to betamethasone-treated birds. Compared to the wet (high FPD) litter treatments, birds on dry (low FPD) litter had greater speed and lower double support time and longer stride length. Turkeys kept on wet litter had a longer stride length compared to dry litter when given saline, whereas in betamethasone-treated birds the means were similar. There were no differences between birds with or without bupivacaine analgesia. Peak vertical force was higher in breed A than B and in birds with a low FPD compared to a high FPD score. It was concluded that breeds A and B did not differ in susceptibility to develop FPD when housed on wet litter but may have natural gait differences. Significant changes in gait parameters were associated with wet litter and with analgesic treatments. The results showed that FPD affected the gait of the turkeys and, combined with evidence of behavioural changes when given analgesia, suggest that footpad lesions are painful.</p

Effect of crude protein concentration and dietary electrolyte balance on litter quality, foot pad dermatitis, growth performance and processing yields in two medium heavy turkey hybrids

1. An experiment was conducted to investigate the effect of crude protein (CP) concentration and dietary electrolyte balance (DEB) on growth performance, processing yields, litter quality and foot pad dermatitis (FPD) in male turkeys from two commercial hybrids. Soya bean meal was replaced by vegetable protein sources selected for lower K concentrations to lower DEB in order to improve litter quality and subsequent quality of foot pads.2. Effects of CP on litter friability and wetness were not consistent during the production period. FPD in turkeys fed on diets with low CP was significantly lower than FPD in turkeys fed on diets with high CP until 84 d. Growth performance was adversely affected at low CP. Processing yields were not affected by CP.3. Litter was significantly dryer in pens of turkeys fed on diets with low DEB than in pens of turkeys fed on diets with high DEB. FPD in turkeys fed on diets with low DEB was significantly lower than in turkeys fed on diets with high DEB. Growth performance and processing yields were adversely affected at low DEB.4. FPD in turkey hybrid A was higher than in turkey hybrid B at 28 d of age. Thereafter, no differences in FPD between turkey hybrids were observed. Growth performance and processing yields were not affected by turkey hybrid.5. Overall, a significant interaction effect of CP × DEB was observed for FCR: in turkeys fed on the high DEB treatment, FCR of turkeys fed on the high CP diets was lower than FCR of turkeys fed on the low CP (LCP) diets whereas on the low DEB treatment, FCR was not affected by CP treatment.6. It was concluded that litter quality can be improved and FPD may be decreased in turkeys fed on diets containing lower CP and DEB levels.<br/

Esophageal Granular Cell Tumor and Eosinophilic Esophagitis: Two Interesting Entities Identified in the Same Patient

We illustrate the case of a 41-year-old male with allergic manifestations since childhood. He sought medical attention for intermittent, progressive dysphagia from which he had been suffering for a number of years, having felt the sensation of a retrosternal lump and a self-limited obstruction to the passage of food. Endoscopy detected a submucosal tumor in the upper third of the esophagus, which was typified, via biopsy, as a granular cell tumor with benign characteristics and probably responsible for the symptoms. Two years later, the patient sought medical attention once again as these symptoms had not abated, hence digestive endoscopy was repeated. This revealed stenosis of the junction between the middle and lower thirds of the organ which had not been detected previously but was passable under gentle pressure. Eosinophilic esophagitis was detected after biopsies were taken. Esophageal manometry identified a motor disorder affecting the esophageal body. Following three months of treatment using fluticasone propionate applied topically, the symptoms went into remission, esophageal stenosis disappeared and the esophageal biopsies returned to normal. This is the first documented case of the link between granular cell tumors and Eosinophilic esophagitis, two different disorders which could cause dysphagia in young patients

Identification of a practical and reliable method for the evaluation of litter moisture in turkey production

1. An experiment was conducted to compare 5 different methods for the evaluation of litter moisture. 2. For litter collection and assessment, 55 farms were selected, one shed from each farm was inspected and 9 points were identified within each shed. 3. For each device, used for the evaluation of litter moisture, mean and standard deviation of wetness measures per collection point were assessed. 4. The reliability and overall consistency between the 5 instruments used to measure wetness were high (α = 0.72). 5. Measurement of three out of the 9 collection points were sufficient to provide a reliable assessment of litter moisture throughout the shed. 6. Based on the direct correlation between litter moisture and footpad lesions, litter moisture measurement can be used as a resource based on-farm animal welfare indicator. 7. Among the 5 methods analysed, visual scoring is the most simple and practical, and therefore the best candidate to be used on-farm for animal welfare assessment

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies