Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL.

Safe discharge of patients with low-risk upper gastrointestinal bleeding (UGIB): can the use of Glasgow-Blatchford Bleeding Score be extended?

INTRODUCTION: Risk stratification of patients with suspected upper gastrointestinal bleeding (UGIB) using either Glasgow-Blatchford Bleeding Score (GBS) or preendoscopy Rockall score to facilitate early safe discharge (GBS=0, pre-Rockall=0) has been reported. This observational study compared score utility and considered the impact of extending the range of GBS or pre-Rockall scores permitting safe discharge. METHODS: Consecutive adult patients presenting to acute medical admissions or the emergency department from September 2008-March 2009 with suspected UGIB had clinical history, vital signs, laboratory and endoscopy results prospectively recorded using electronic databases. GBS, pre-Rockall scores and a composite endpoint (blood transfusion, endoscopic therapy, interventional radiology, surgery or 30-day mortality) were calculated. RESULTS: 388 patients with suspected UGIB were identified of which 92.3% were admitted (median (range) GBS=5 (0-19) and pre-Rockall=2 (0-11)) and 7.7% discharged (GBS=0 (0-4) and pre-Rockall=0 (0-4)). 186 (47.9%) underwent in-patient endoscopy. 151 (38.9%) were found to have the composite endpoint with 77.5% having transfusion, 45.7% endoscopic treatment and an 8.0% mortality within 30 days. AUROC (95% CI) for 30-day composite endpoint was 0.92 (0.89-0.94) using GBS and 0.75 (0.70-0.80) using pre-Rockall scores. Analysis using different GBS thresholds demonstrated that GBS=0, GBS ≤1 and GBS≤2 had superior utility in identifying freedom from an adverse clinical outcome at 30-days than pre-Rockall score 0. CONCLUSIONS: GBS is superior to pre-Rockall score in identifying patients with suspected UGIB who have a low likelihood of an adverse clinical outcome and can be considered for early discharge. Diagnostic performance at different thresholds suggests that patients with GBS≤2 could be considered for early discharge, doubling the number of eligible patients (15.2 to 32.5%). This has important patient safety and resource implications.

The placenta in pre-eclampsia and intrauterine growth restriction: studies on exchange surface areas, diffusion distances and villous membrane diffusive conductances.

We test the null hypothesis that the morphometric diffusive conductance of the placental villous membrane does not alter in pregnancies complicated by intrauterine growth restriction (IUGR) or pre-eclampsia (PE). Placentas were collected from cases of normotensive IUGR, pure PE, PE+IUGR and from control pregnancies. Microscopical fields on formalin-fixed, trichrome-stained histological sections were randomly sampled for location and orientation. Using stereological methods, the exchange surface areas of peripheral (terminal and intermediate) villi and their fetal capillaries and the arithmetic and harmonic mean thicknesses of the villous membrane (maternal aspect of trophoblast to luminal aspect of vascular endothelium) were estimated. An index of the variability in thickness of this membrane, and an estimate of its oxygen diffusive conductance, was derived secondarily. Group comparisons were drawn using two-way analysis of variance to identify main effects (of PE or IUGR) and interaction effects (between PE and IUGR). PE did not have significant effects on placental morphology and there were no significant effects of PE or IUGR on membrane thickness or its variability. In contrast, IUGR (with or without PE) was associated with reduced surface areas and this was the principal factor leading to a smaller membrane diffusive conductance in these placentas. When account was taken of fetal mass, specific conductance showed no effects of PE or IUGR despite the mass-specific conductance in pure IUGR placentas appearing to be smaller than that in controls. The decline in total conductances is indicative of perturbations operating at the levels of villous trophoblast and fetal vasculature and these may contribute to fetal hypoxic stress.