Identification of wild-type transthyretin cardiac amyloidosis in patients with carpal tunnel syndrome surgery (CACTuS)

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative cardiomyopathy with a poor prognosis. The condition is associated with carpal tunnel syndrome (CTS), which often precedes the ATTRwt diagnosis by several years. The aim of the study was (i) to screen patients with a recent history of CTS for ATTRwt using red flags, (ii) to determine whether patients with screened ATTRwt had less advanced disease compared with patients with clinical ATTRwt, and (iii) to assess the sensitivity and specificity of known red flags in ATTRwt. METHODS AND RESULTS: Patients aged ≥60 years at the time of CTS surgery were invited for screening. Red flags were defined as elevated biomarker levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) or cardiac troponin, an electrocardiogram pattern associated with ATTRwt, left ventricular hypertrophy (LVH), and impaired longitudinal strain with apical sparring. All patients with a red flag were referred for a diagnostic scintigraphy. Patients with ATTRwt diagnosed by screening were compared with patients with clinical ATTRwt (n = 51) matched by age, gender, and CTS surgery. Among the 120 enrolled subjects (mean age 74.5 years, 90% male), the suspicion of ATTR was raised in 67 (55.8%), and 10 (8.3%) were diagnosed with ATTRwt. Patients identified with ATTRwt were predominantly asymptomatic and had mildly elevated NT-proBNP, mildly increased LVH, preserved left ventricular ejection fraction, and systolic longitudinal function, which differed significantly from clinical ATTRwt controls (P < 0.001). CONCLUSIONS: The study found an ATTRwt prevalence of 8.3% in a population of age and gender-selected patients with a recent history of CTS. The identified patients with ATTRwt had less structural and functional cardiac involvement than clinical ATTRwt controls

Disability and return to work after MRI on suspicion of scaphoid fracture: Influence of MRI pathology and occupational mechanical exposures.

OBJECTIVES:We aimed to determine the prognosis after early MRI on clinical suspicion of scaphoid fracture, hypothesising that MRI pathology is associated with more disability and that MRI pathology and high occupational mechanical hand-arm exposures are associated with slower return to work (RTW). METHODS:We conducted a follow-up study of a cohort of 469 patients, who were scanned in the period 2006 to 2010. The respondents constituted our cohort for disability analysis and the subset that was in the labour market at the time of the trauma constituted our sub-cohort for RTW analysis. Questionnaires included disability scores, job title, and lifestyle factors. Job titles were linked with a job exposure matrix to estimate occupational exposures. Register information was obtained on time until RTW. We used logistic regression analysis of disability and Cox regression analysis of time until RTW. RESULTS:The proportion that responded was 53% (249/469) for the disability analysis and 59% (125/212) for the RTW analysis. The mean age at follow up was 43.5 years, the mean time since trauma was 4.8 years, 53% had injury of the dominant hand, and 54% had MRI pathology. Men constituted 43% of the cohort and 56% of the sub-cohort. MRI pathology was not associated with more disability [e.g., for a 'Disabilities of the Arm Shoulder and Hand'-score ≥20 the odds ratio was 0.58 (95% confidence interval 0.26-1.17)]. Patients without MRI pathology and with low occupational exposures were off work for an average of four weeks. Patients with MRI pathology or high occupational exposures were off work for twice as long time. CONCLUSION:MRI pathology was not associated with more disability. For patients, who were in the labour market at the time of the trauma, MRI pathology and high occupational mechanical hand-arm exposures were associated with slower RTW

Functional and immunochemical characterisation of different antibodies against the erythropoietin receptor

Since it was discovered that the hematopoietic hormone erythropoetin (EPO) exerts neuroprotective effects in the CNS, many studies on the EPO receptor (EPOR) function and localisation in the CNS have been performed. For this purpose, commercially available anti-EPOR antibodies have often been applied. As the literature data on these antibodies show inconsistencies, we here systematically compared six frequently used, commercially available EPOR antibodies for different applications. Five of the antibodies appeared to specifically recognize recombinant rat and human EPOR in HEK293 cells by Western blotting, but the same antibodies yielded different and inconsistent results when human UT-7 cells or rat brain tissue were applied. Immunocytochemical staining of EPOR-transfected HEK cells only produced consistent results with three of the six antibodies. All antibodies stained neurons in rat brain sections, but with large differences in the staining pattern and only the C-20 EPOR antibody was found to label astrocytes. Since EPOR antibodies have been applied in several studies as EPOR antagonists, we further tested the antibodies for their capacity to functionally block the EPO EPOR interaction in a cellular signalling system with STAT-5 phosphorylation as readout. Here, only the MAB307 antibody showed a partial effect at concentrations of 5 50 μg/ml