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Background: We previously reported that donanemab slows global and regional increase in flortaucipir standardized uptake value ratios (SUVRs)1. In addition to SUVR, a method to estimate spatial distribution of flortaucipir (FTP) uptake might provide valuable and complementary information. Here, we apply the previously developed Extent method to estimate the spread of FTP uptake in PET images and present comparisons against neocortical SUVR for the measurement of treatment effect in the TRAILBLAZER‐ALZ trial. We performed vertex‐wise statistical comparisons. Method: Subjects in the phase 2 TRAILBLAZER‐ALZ study completed FTP and florbetapir PET scans and MRIs at baseline and 18‐months. Flortaucipir images were processed using standard techniques2 and normalized to the cerebellum crustaneous reference region3. Each FTP image was converted to a z‐score image relative to sixteen young cognitively normal (YCN) subjects. Clusters with z‐scores smaller than a false discovery rate corrected p‐value of 0.01 were retained within a predefined neocortical mask. The neocortical mask and thresholds were selected based on previous data to maximize signal to noise ratio in 18‐month change of mild AD subjects. Extent is the ratio of voxels in this predefined mask that have abnormally elevated tau, defined as at least 2.32*SD above the mean of YCNs (values range between 0‐1). The primary outcome was 18‐month change in Extent and MUBADA2 SUVR between placebos and donanemab treated subjects. We performed vertex‐wise group comparisons to capture the differences in tau burden. Result: Both Extent and MUBADA showed significant difference between treated and placebo subjects (Figure 1). The 18‐month change (SUVR and Extent) surface maps of the treated and placebo groups show larger spread of FTP in the superior, middle and medial orbito‐frontal regions (Figure 2 & 3). The difference and p‐value maps show clusters of vertices in the inferior temporal, parahippocampal, supramarginal, middle, medial and superior frontal regions as being significantly different. Conclusion: Subjects treated with donanemab have significantly lesser flortaucipir distribution by Extent compared to placebo, and differences in surface maps of intensity and spread of FTP. Clusters in temporal, parietal, and frontal regions were significantly different. In addition to intensity differences, spatial distribution was different between treatment groups. [ABSTRACT FROM AUTHOR]

Introduction: Klunk et al. recently proposed a means of standardizing quantitation of amyloid burden from positron emission tomography scans to a common Centiloid scale, and we have applied that method to florbetapir. Methods: Florbetapir and Pittsburgh compound B scans were acquired for 46 mixed clinical presentation subjects within 18 ± 20 days. Florbetapir and Pittsburgh compound B cortical standardized uptake value ratio (SUVr) values were well correlated for both standard Centiloid (R2 = 0.894) and Avid (R2 = 0.901) volume of interests (VOIs). The methods of Klunk et al. were applied to establish a conversion first from florbetapir SUVr values obtained using standard Centiloid VOIs to Centiloids and then from Avid VOIs (Joshi et al.) to Centiloids. Results: The equation for conversion of florbetapir SUVr from Avid VOIs to the Centiloid scale was as follows: Florbetapir Centiloids = 183 × SUVrAvid − 177. The threshold that discriminated neuropathologically verified none or sparse versus moderate to frequent plaques in autopsy‐confirmed data is 24.1 Centiloids. Discussion: These findings may allow improved tracer‐independent amyloid quantitation. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's Disease (AD) patients showing neocortical Flortaucipir (FTP) tau levels above predetermined cutoffs based on the likelihood of disease progression are enrolled in Lilly trials. However, patients below the cutoffs can also exhibit disease progression, and clinical decline. These patients might be earlier in the course of disease progression and may benefit the most from therapy. The objective of this study is to apply data‐driven methods on regional tau measurements at baseline to identify a relatively homogeneous patient population showing earlier signals of tau. Method: A standardized uptake value ratio (SUVr) from a weighted composite region (MUBADA;Devous et al,JNM,2017) with respect to cerebral white matter reference signal intensity (Southekal et al,JNM,2018) was calculated using baseline FTP (n=1093) images from AVID FTP development studies (AV1451‐A05:NCT02016560) and Lilly clinical trials (EXPEDITION‐3:NCT01900665, NAVIGATE‐AD:NCT02791191, and AMARANTH:NCT02245737). Using the cutoff of 1.11, we identified a cohort of 431 subjects that were negative by MUBADA. Diagnostic breakdown included 67 cognitively‐normal, 135 mild‐cognitive‐impairment, and 229 AD subjects. Within this cohort, we calculated reference‐region independent, min‐max scaled regional tau measurements in 68 regions from FreeSurfer FsAverage template. An affinity propagation clustering analysis was applied to detect homogeneous subgroups showing patterns of similar tau uptake. Two distinct subgroups—FTPEarly (n=151), and FTPUndetected (n=280), names reflecting their tau uptake levels— emerged in the cohort. The groups were compared on clinical, cognitive, and genetic characteristics using Analysis‐Of‐Covariance. Result: FTPEarly group demonstrated relatively higher baseline plasma‐tau levels (p‐tau217) and pattern of elevated FTP uptake in inferior‐temporal, fusiform, entorhinal, and para‐hippocampal regions (P<0.01 for all) compared to FTPUndetected group. In FTPEarly group, 98% were MCI or AD, 90% were amyloid+, and 69% were APOE4‐carriers, whereas in FTPUndetected group, the prevalence of MCI or AD, amyloid positivity, and APOE4‐carriers dropped to 76%, 43%, and 37%, respectively. When evaluated on longitudinal sub‐population, FTPEarly patients progressed faster than FTPUndetected patients on FTP SUVr (P<0.01) and cognitive measures (ADAS; P<0.01). Conclusion: Data‐driven methods identify visually difficult to recognize FTPEarly group characterized by distinct neuroimaging patterns and paralleled by relatively homogeneous clinical, genetic, and cognitive profile. These methods hold promise for targeting enrollment of FTPEarly patient populations into clinical trials. [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease, neurofibrillary tangle (NFT) burden can be characterized in postmortem staining and in vivo NFT‐specific flortaucipir PET by increases in intensity and spatial distribution. Previous work compared intensity based standard uptake value ratios (SUVRs) from Early Tau and MUBADA volumes of interest (VOIs) in detecting Braak stage pathology. We propose a measure called Extent to quantify the spatial distribution of NFT‐specific uptake in flortaucipir PET from the Phase III study AV‐1451‐A16 and compare against Early Tau and MUBADA SUVRs in detecting Braak stage pathology and post‐mortem amyloid burden. Methods: This retrospective analysis of the AV‐1451‐A16 study included 60 subjects that underwent ante‐mortem flortaucipir imaging and post‐mortem assignment of Braak stages and Thal/CERAD scoring for amyloid burden. The processing of the flortaucipir scans and the recording of neuropathological findings were performed as previously described except cerebellum crustaneous was used as a reference region. Extent was calculated by 1) creating a Z‐score image using 16 young cognitively normal controls, 2) retaining voxel clusters with Z‐scores smaller than a false discovery corrected p‐value of 0.01, and 3) calculating the ratio of the number of surviving voxels against the total number of voxels in the mask. Flortaucipir positivity was defined as greater than 2.5 SD of the mean of young controls for Early Tau and MUBADA SUVRs and as non‐zero for Extent. Amyloid positivity was defined by a Thal/CERAD scoring of 2 or higher and compared to flortaucipir positivity using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Extent detected subjects with flortaucipir positivity comparably to Early Tau in Braak stages I, II, and III while detecting more subjects with flortaucipir positivity in Braak stages V and VI than Early Tau and MUBADA (Table 1 and Figure 1). For amyloid positivity, Extent had the highest sensitivity (79.62%) and NPV (29.42%) while MUBADA had the highest specificity (87.50%) and PPV (97.06%) (Table 2). Conclusion: Based on the Correspondence to post‐mortem staining, the Extent measure of flortaucipir spatial distribution may provide benefit over intensity based SUVRs in detecting flortaucipir and amyloid positive subjects for inclusion in future studies. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of spontaneous regression of extensive colorectal cancer peritoneal metastases in an 82-year-old female patient. The patient initially presented with abdominal pain and weight loss, and a CT scan revealed ascites and omental nodularity. After discontinuing methotrexate, an updated CT scan showed resolution of ascites and only a single residual omental nodule. The patient remains asymptomatic with no therapy 20 months after diagnosis. The article highlights the potential importance of immune responsiveness in the subset of colorectal cancer with DNA mismatch repair deficiency. [Extracted from the article]

We report, for the first time, the atmospheric pressure synthesis of nonagglomerated nanoparticles (20–60 nm in diameter) of the uncommon monoclinic phase of some heavy rare earth sesquioxides RE2O3 (RE=Dy, Ho, Er, Tm, and Yb). The RE2O3 nanoparticles, prepared by a flame synthesis process, were characterized by X-ray diffraction, transmission electron microscopy, and electron energy loss spectroscopy. Monoclinic nanoparticles were formed when the flame temperature was sufficiently high; lower temperatures led to the formation of the normal cubic (C-type) phase. We explain the formation of the uncommon monoclinic phase on the basis of pressure–temperature phase equilibria, and the extra internal pressure induced by surface curvature of the nanoparticles. [ABSTRACT FROM AUTHOR]

Background: To assess the prevalence and causes of visual impairment in patients with craniosynostotic syndromes of Apert, Crouzon, Pfeiffer, Saethre–Chotzen and craniofrontonasal dysplasia. Methods: The medical records of patients who attended the Craniofacial Clinic at two large paediatric hospitals in Sydney, Australia between 1983 and 2004 were retrospectively reviewed. Presenting visual acuity (VA) was assessed using tests appropriate to age and cognition: ‘fix and follow’ in infants (<18 months old), Teller card acuity in preverbal children (18 months to less than 3 years old), Kay picture test or Sheridan–Gardiner test in children aged between 3 and less than 6 years and Snellen chart in those aged 6 years or older. Visual impairment was defined as the inability to fix and follow or presenting VA < 6/12 in the better eye. Amblyopia was defined as a two-line difference in VA between both eyes in the absence of an organic eye disease. Results: Sixty-three patients with craniosynostotic syndromes were identified, of whom 55 had VA assessed at the first visit. Of these 55, 19 (35.5%) had bilateral visual impairment and 5 (9.1%) had unilateral visual impairment. Causes of visual impairment include amblyopia (16.7%), ametropia (25%), optic atrophy (16.7%) and exposure keratopathy (4.2%). Risk factors for amblyopia include strabismus (43.3%), astigmatism (≥1.5 dioptres) (39.5%), hypermetropia (18.4%) and anisometropia (≥1.5 dioptre difference between both eyes) (15.8%). Six of the 63 patients (9.5%) had papilloedema; those who were followed up showed gradual resolution of papilloedema following timely decompressive surgery. Conclusions: A high prevalence of visual impairment in patients with craniosynostotic syndromes was found, almost half of them due to potentially correctable causes, including amblyopia and ametropia. Optic atrophy remains an important cause of visual impairment. Further studies are needed to assess the timing and efficacy of intervention for modifiable causes of visual loss in craniosynostotic syndromes. [ABSTRACT FROM AUTHOR]

An 83-year-old woman presented with primary multifocal cutaneous B-cell lymphoma, presenting as discrete nodules on the right pinna and nail-bed of the left middle finger, diffuse swelling and erythema of several other nail-beds of the fingers and toes, with associated pincer nail deformity and rhinophyma. Because of the involvement of several sites not amenable to radiotherapy, she was treated with oral cyclical chlorambucil with good result. [ABSTRACT FROM AUTHOR]

An 83-year-old woman presented with primary multifocal cutaneous B-cell lymphoma, presenting as discrete nodules on the right pinna and nail-bed of the left middle finger, diffuse swelling and erythema of several other nail-beds of the fingers and toes, with associated pincer nail deformity and rhinophyma. Because of the involvement of several sites not amenable to radiotherapy, she was treated with oral cyclical chlorambucil with good result.