Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest highresolution computed tomography (HRCT) as the gold standard for PAVMs.All consecutive adult patients referred for HHT screening underwent a chest HRCT (n5299), TTCE (n5281), arterial blood gas analysis (n5291), shunt fraction measurement (n5111) and chest radiography (n5296).TTCE was positive in 87 (58.8%), 12 (16.7%) and four (6.7%) patients, and chest HRCT was positive in 54 (36.5%), three (4.2%) and zero (0%) patients with a definite, possible and negative clinical diagnosis of HHT, respectively. Two patients with a negative TTCE were diagnosed with PAVMs after computed tomography; in both cases the PAVMs were too small to be treated by embolotherapy. The sensitivity of TTCE was 97% (95% confidence interval (CI) 93.6-98.3) and negative predictive value 99% (95% CI 96.9-99.8). The other diagnostic tests showed a considerable lower diagnostic value.The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.KEYWORDS: Contrast echocardiography, hereditary haemorrhagic telangiectasia, pulmonary arteriovenous malformations A pulmonary arteriovenous malformation (PAVM) is a direct communication between a pulmonary artery and pulmonary vein. A PAVM results in a right-to-left shunt (RLS) causing hypoxaemia and risk of paradoxal embolism through bypassing the filtering capillary network. Complications occurring in patients with PAVM and hereditary haemorrhagic telangiectasia (HHT) are stroke (10-19%), transient ischaemic attacks (6-37%), cerebral abscess (5-9%), migraine headaches, seizures, massive haemoptysis and (spontaneous) haemothorax [1][2][3]. Antibiotic prophylaxis prior to procedures carrying the risk of bacteraemia is recommended [3][4][5]. At least 80% of PAVMs are associated with HHT [3]. HHT is an autosomal dominant disorder characterised by vascular abnormalities varying from small telangiectases to large arteriovenous malformations. The clinical diagnosis is based on the Curaçao criteria [6]. Based on genetic analysis, HHT is divided into types 1 and 2, corresponding with mutations in the genes ENG and ACVRL1, coding for endoglin and activin A receptor type-like kinase 1, respectively [7,8]. The prevalence of PAVM, as documented by chest high-resolution computed tomography (HRCT), in all HHT patients is 20-45% [4,9]. The PAVM prevalence differs between these two subtypes, in HHT type 1 the prevalence is 48%, whereas the prevalence in HHT type 2 is 5% [10]. PAVMs can...

Background: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions. Case: A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal. Conclusion: To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.

Funding Acknowledgements Type of funding sources: None. Background. Knowledge about the association between symptoms and rhythm status (symptom-rhythm correlation) has potential clinical implications as it may identify patients with atrial fibrillation (AF) who profit from rhythm control in regard to reduction in symptom burden and improvement in quality of life. However, standardized strategies to assess symptom-rhythm correlation in AF patients are currently not available. Purpose. This study aimed to assess symptom-rhythm correlation in patients with persistent AF using electrical cardioversion (ECV) as a diagnostic probe. Methods. We used ECV to examine symptom-rhythm correlation in 81 patients with persistent AF. The presence of self-reported symptoms before ECV and at the first outpatient AF clinic follow-up visit (within 1-month) was assessed to determine the prevalence of a symptom-rhythm correlation (defined as self-reported symptoms present during AF and absent in sinus rhythm or absent in AF and yet relief during sinus rhythm). The symptom-rhythm correlation was absent in patients with symptoms before ECV who remained symptomatic during sinus or in patients with symptoms prior to ECV and without symptoms in AF after ECV. Asymptomatic patients before ECV with or without symptoms in AF or sinus rhythm afterwards had no symptom-rhythm correlation as well. The symptom-rhythm correlation was unevaluable in patients who were symptomatic in AF before ECV and at the first outpatient AF clinic follow-up visit. In addition, predominant self-reported symptoms (symptoms with highest self-reported symptom burden) were assessed to evaluate the symptom patterns around ECV. Intra-individually variable symptom patterns were defined as changes in predominant self-reported symptoms within patients around ECV. Results. Symptom-rhythm correlation was assessed in all patients. Only in 18 patients (22%), a symptom-rhythm correlation could be documented. Twenty-eight patients (35%) did not show any symptom-rhythm correlation and 35 patients (43%) had an unevaluable symptom-rhythm correlation as these patients were in symptomatic AF both at baseline and at the first outpatient AF clinic follow-up visit. Importantly, self-reported symptom patterns around ECV were intra-individually variable in 10 patients (12%) without symptom-rhythm correlation (of which 9 patients (11%) had AF recurrence) and in 2 patients (2%) with an unevaluable symptom-rhythm correlation. Conclusions. In patients with persistent AF, the prevalence of a symptom-rhythm correlation around ECV is low, but ECV often changes symptom pattern. Further studies are warranted to identify more optimal strategies to assess symptom-rhythm correlation in patients with persistent AF. Abstract Figure. Symptom-rhythm correlation and patterns