Good Laboratory Response Research Articles

636 LOOKING AT THE BIGGER PICTURE: FROM ACUTE MYOCARDITIS TO THE DIAGNOSIS OF A MULTISYSTEMIC DISEASE

Abstract A 49-year-old man without cardiovascular risk factors, recently diagnosed of asthma and rino-sinusal polyposis, entered the Emergency Department for chest pain, shortness of breath and non-productive cough. The patient was in stable conditions. Laboratory exams showed eosinophilic leucocytosis (WBC 33.000/sqmm, 60% eosinophils) and a mild elevation of C-reactive protein (CRP 2,2 mg/dL). ECG showed a sinus rhythm with flat T-waves in the antero-lateral leads. Troponin values were high but not suggestive of acute myocardial damage (9900 - 9700 ng/L). Echocardiography showed normal biventricular volumes with moderately depressed left ventricular ejection fraction (40%), hypokinesia of the antero-lateral wall in the mid-apical segments and mild pericardial effusion. During the hospital stay he developed progressive respiratory failure, and he was transferred to a tertiary center to perform an endomyocardial biopsy (EMB) in the suspicion of acute myocarditis. EMB showed multifocal interstitial and sub-endocardial inflammatory infiltrates (predominantly eosinophils) with foci of myocellular damage, small vessels wall inflammation with hypertrophy of the muscular tunica. The overall picture was consistent with diffuse moderate eosinophilic myocarditis with small vessels vasculitis. The right heart cath performed in the same procedure and during diuretic therapy showed a normal hemodynamic profile (RAP 5 mmHg, PCWP 13 mmHg, CI 3,7 L/min/sqm). The patient was treated with high dose steroids, first intravenously (methylprednisolone 125 mg/day for three days), then orally (prednisone 80 mg/day) in slow decalage until a maintenance dose of 12.5 mg daily. The recent-onset of asthma with hyper-eosinophilia and rhino-sinus-bronchial syndrome in the light of the present cardiac condition was consistent with eosinophilic granulomatosis with polyangiitis (EGPA). Chest CT showed two areas of ground glass at the left superior and right superior lobes. Other potential haematological and infective causes of hyper eosinophilia and viral causes of myocarditis were ruled out. After the treatment, his clinical conditions improved, ECG was completely normalized, left ventricular systolic function improved (LVEF 50%) and eosinophil count was significantly reduced (Eosinophils 830/sqmm, 8,9%), whereas CT showed resolution of the lung infiltrates. One month after discharge, the patient was still asymptomatic. Cardiac MRI showed normal biventricular ejection fraction (LVEF 55%) with circumferential subendocardial fibrosis involving only the left ventricle. EMB showed a complete resolution of the inflammatory infiltrates and of the vasculitic aspects. Eosinophil count was elevated (5660/sqmm, 36%). Therefore, steroidal dose was raised to 50 mg/day. After rheumatologic evaluation, a steroidal sparing strategy with cyclophosphamide and anti-IL5 antibody Mepolizumab was adopted, with good laboratory response. Three months later, cardiac MRI showed no signs of active disease. No further EMB was scheduled. Through the presentation of this unusual cause of acute myocarditis, we want to underscore the importance of an early referral to a tertiary level center of patients with suspected myocarditis and reduced systolic function and the usefulness of histology to guide medical therapy in specific forms of myocarditis that can lead to a potential complete recovery.

Serum Protein Abundance in Children with Sickle Cell Disease at Baseline, during Acute Pain Crisis, and on Hydroxyurea - Compared to Children with Other Pediatric Diseases

Introduction: Sickle cell disease (SCD) is a multisystem disease, with substantial variation in presentation and clinical course. Many biomarkers have been described both during steady state and with complications, but comparison between SCD and other pediatric disease are lacking. In this prospective study we used a multiplex dual antibody sandwich immunoassay and compared the abundance of 103 serum proteins in 130 children with SCD, 51 morbidly obese children (BMI percentile > 99%), 29 children with inflammatory bowel disease at initial diagnosis, 186 children with pediatric solid tumors and 151 healthy controls. Serum samples of children with SCD were either taken at baseline (59 samples), on the day of admission for pain crisis (27 samples), or while adherent to hydroxyurea for at least 9 months (44 samples). For each set of 5 disease samples, 3 healthy control samples were selected that were matched by age, gender and race. Type of SCD, laboratory values and disease severity based on history of SCD complication were recorded.Methods: The relative concentration of 103 different serum proteins was measured with a customized quantibody array (Raybiotech, Inc.). Disease and control samples were processed in a random block design stratified by disease, sex, and age to minimize the effect of sample preparation and technician processing. The slides were developed with Alexa Flour 555- conjugated streptavidin and the signal was quantified using a laser scanner (GenePix® 4000A, Molecular Devices Corporation). Measurements from the different PMT voltages were combined into a single composite scan, which was then background corrected and normalized by setting the mean of each array block to the global mean. A linear mixed effects model was constructed for each protein that included gender, race, and disease subgroups as fixed effects factors, with the sample (nested within subject) treated as a random factor. This model was fitted to each protein by restricted maximum likelihood using the lmer function in the R package lme4. Contrasts were constructed using the multcomp package to generate p-values for comparisons of interest. Within each comparison, the false discovery rate was controlled at 5% using the method of Benjamini and Hochberg.Results: Sixty-one serum proteins were significantly different between children with SCD and healthy subjects, 57 serum proteins between children with SCD and solid tumors, 38 serum proteins between children with SCD and obesity, and 14 serum proteins between children with SCD and inflammatory bowel disease. One-third of the serum proteins (19) were unique for SCD, as they were not significantly different from healthy children in any other of the pediatric diseases examined. Compared to serum of healthy children, 44 proteins were significantly different in children with severe SCD, 46 proteins in children with SCD suffering from an acute pain crisis, 45 proteins in children with SCD on hydroxyurea, and 42 proteins in children with clinically mild sickle cell disease (predominantly Hemoglobin SC disease). Surprisingly only one protein (CCL2) was significantly different between children with SCD at baseline and during an acute pain crisis. Hydroxyurea therapy only caused seven proteins to become significantly different from their pretreatment baseline; and only eight proteins were statistically different at a well baseline visit between children classified as having clinically mild versus severe disease. When compared to children with severe sickle cell disease, only 2 proteins (HGF and BDNF) were lower in both children with clinically mild SCD and in those taking hydroxyurea.Conclusion: Distinct SCD-specific abundance changes in serum proteins were identified compared to healthy controls and other pediatric disease. Perhaps most interestingly, the protein abundance profiles of the 103 studied proteins in pediatric SCD patients are almost identical between their baseline state and during an acute pain crisis; and minimal protein changes occurred in children with sickle cell disease who were stably taking hydroxyurea with an otherwise good laboratory response (increased MCV and Hgb F). Differences in serum protein abundance profiles could help distinguish mild from severe SCD and should be explored in larger studies. DisclosuresNo relevant conflicts of interest to declare.

FRI0352 Treatment of refractory takayasu arteritis with tocilizumab: seven italian patients from a single referral center.

BackgroundTakayasu arteritis (TA) is an inflammatory large-vessel panarteritis resulting in vessel stenosis, occlusion or aneurysm formation1. Medical therapy with steroids and immunosuppressive agents is the cornerstone of TA although a...

Clinical and Prognostic Implications of the Initial Response to Aspirin in Patients With Acute Coronary Syndrome

Increased platelet reactivity and decreased response to antiplatelet drugs may result in recurrent ischemic events after acute coronary syndrome (ACS). We evaluated laboratory response to aspirin in patients with ACS before and after percutaneous coronary intervention (PCI) and assessed its effect on major adverse clinical events. Sixty-three consecutive patients with ACS were tested for response to aspirin by light transmittance aggregometry (LTA) and the IMPACT-R test (with arachidonic acid) before and 2 to 4 days after PCI and clopidogrel loading. Patients were followed for clinical events up to 15 months from PCI. Response to aspirin improved significantly after PCI and clopidogrel treatment (mean arachidonic acid-induced LTA decreased from 34.9 ± 3.35% before PCI to 15.2 ± 2.2% and surface coverage increased from 2.2 ± 0.27% to 6.2 ± 0.6%, p <0.0001 for the 2 methods). Improved response to aspirin after PCI correlated with response to clopidogrel (LTA and IMPACT-R, p <0.01). Patients with good laboratory response to aspirin before but not after PCI had a significantly lower major cardiovascular event rate during 15-month follow-up in multivariate analysis. In conclusion, laboratory response to aspirin is highly dynamic in patients with ACS. Improved response to aspirin after PCI may result from stabilization of coronary artery disease and/or clopidogrel treatment. Laboratory response to aspirin before PCI and clopidogrel loading is a sensitive marker for platelet reactivity that correlates with clinical outcome in patients with ACS.