Indolent Small Intestinal CD4+ T-cell Lymphoma Is a Distinct Entity with Unique Biologic and Clinical Features

Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease

Fall Risk is Not Black and White

Objective: To determine whether previously reported racial differences in fall rates between White and Black/African American is explained by differences in health status and neighborhood characteristics. Design: Prospective cohort Setting: Community Participants: The study included 550 White and 116 Black older adults in the Greater Boston area (mean age: 78 years; 36% men) who were English-speaking, able to walk across a room, and without severe cognitive impairment. Measurements: Falls were prospectively reported using monthly fall calendars. The location of each fall and fall-related injuries were asked during telephone interviews. At baseline, we assessed risk factors for falls, including sociodemographic characteristics, physiologic risk factors, physical activity, and community-level characteristics. Results: Over the mean follow-up of 1,048 days, 1,539 falls occurred (incidence: 806/1,000 person-years). Whites were more likely than Blacks to experience any falls (867 versus 504 falls per 1,000 person-years; RR [95% CI]: 1.77 [1.33, 2.36]), outdoor falls (418 versus 178 falls per 1,000 person-years; 1.78 [1.08, 2.92]), indoor falls (434 versus 320 falls per 1,000 person-years; 1.44 [1.02, 2.05]), and injurious falls (367 versus 205 falls per 1,000 person-years; 1.79 [1.30, 2.46]). With exception of injurious falls, higher fall rates in Whites than Blacks were substantially attenuated with adjustment for risk factors and community-level characteristics: any fall (1.24 [0.81, 1.89]), outdoor fall (1.57 [0.86, 2.88]), indoor fall (1.08 [0.64, 1.81]), and injurious fall (1.77 [1.14, 2.74]). Conclusion: Our findings suggest that the racial differences in fall rates may be largely due to confounding by individual-level and community-level characteristics

Diagnosing celiac disease by video capsule endoscopy (VCE) when esophogastroduodenoscopy (EGD) and biopsy is unable to provide a diagnosis: a case series

Video capsule endoscopy (VCE) is mainly used to evaluate patients with celiac disease in whom their course after diagnosis has been unfavorable and the diagnosis of adenocarcinoma, lymphoma or refractory celiac disease is entertained, but it has been suggested that VCE could replace esophagogastroduodenoscopy (EGD) and biopsy under certain circumstances. We report a single center case series of 8 patients with suspected celiac disease who were diagnosed by VCE. EGD and biopsy had been performed in 4 patients resulting in a negative biopsy, declined by 2, and contraindicated in 2 due to hemophilia and von Willebrand disease. In all patients, mucosal changes of scalloping, mucosal mosaicism and reduced folds were seen in either the duodenum or jejunum on VCE. Follow-up in 7 patients demonstrated improvement in either their serological abnormalities or their presenting clinical features on a gluten-free diet. Our case series demonstrates that VCE and the visualization of the characteristic mucosal changes of villous atrophy may replace biopsy as the mode of diagnosis when EGD is either declined or contraindicated, or when duodenal biopsies are negative and there remains a high index of suspicion. Further study is needed to clarify the role and cost of diagnosing celiac disease with VCE

Classification of videocapsule endoscopy image patterns: comparative analysis between patients with celiac disease and normal individuals

Quantitative disease markers were developed to assess videocapsule images acquired from celiac disease patients with villous atrophy, and from control patients. Capsule endoscopy videoclip images (576 × 576 pixels) were acquired at 2/second frame rate (11 celiacs, 10 controls) at regions: 1. bulb, 2. duodenum, 3. jejunum, 4. ileum and 5. distal ileum. Each of 200 images per videoclip (= 100s) were subdivided into 10 × 10 pixel subimages for which mean grayscale brightness level and its standard deviation (texture) were calculated. Pooled subimage values were grouped into low, intermediate, and high texture bands, and mean brightness, texture, and number of subimages in each band (nine features in all) were used for quantifying regions 1-5, and to determine the three best features for threshold and incremental learning classification. Classifiers were developed using 6 celiac and 5 control patients' data as exemplars, and tested on 5 celiacs and 5 controls. Pooled from all regions, the threshold classifier had 80% sensitivity and 96% specificity and the incremental classifier had 88% sensitivity and 80% specificity for predicting celiac versus control videoclips in the test set. Trends of increasing texture from regions 1 to 5 occurred in the low and high texture bands in celiacs, and the number of subimages in the low texture band diminished (r2 > 0.5). No trends occurred in controls. Celiac videocapsule images have textural properties that vary linearly along the small intestine. Quantitative markers can assist in screening for celiac disease and localize extent and degree of pathology throughout the small intestine

Robust spectral analysis of videocapsule images acquired from celiac disease patients

Dominant frequency (DF) analysis of videocapsule endoscopy images is a new method to detect small intestinal periodicities that may result from mechanical rhythms such as peristalsis. Longer periodicity is related to greater image texture at areas of villous atrophy in celiac disease. However, extraneous features and spatiotemporal phase shift may mask DF rhythms. The robustness of Fourier and ensemble averaging spectral analysis to compute DF was tested. Videocapsule images from the distal duodenum of 11 celiac patients (frame rate 2/s and pixel resolution 576 × 576) were analyzed. For patients 1, 2, ... 11, respectively, a total of 10, 11, ..., 20 sequential images were extracted from a randomly selected time epoch. Each image sequence was artificially repeated to 200 frames, simulating periodicities of 0.2, 0.18, ..., 0.1Hz, respectively. Random white noise at four different levels, spatiotemporal phase shift, and frames with air bubbles were added. Power spectra were constructed pixel-wise over 200 frames, and an average spectrum was computed from the 576 × 576 individual spectra. The largest spectral peak in the average spectrum was the estimated DF. Error was defined as the absolute difference between actual DF and estimated DF. For Fourier analysis, the mean absolute error between estimated and actual DF was 0.032 ± 0.052Hz. Error increased with greater degree of random noise imposed. In contrast, all ensemble average estimates precisely predicted the simulated DF. The ensemble average DF estimate of videocapsule images with simulated periodicity is robust to noise and spatiotemporal phase shift as compared with Fourier analysis. Accurate estimation of DF eliminates the need to impose complex masking, extraction, and/or corrective preprocessing measures

Exploring the relation between remotely sensed vertical canopy structure and tree species diversity in Gabon

Mapping tree species diversity is increasingly important in the face of environmental change and biodiversity conservation. We explore a potential way of mapping this diversity by relating forest structure to tree species diversity in Gabon. First, we test the relation between canopy height, as a proxy for niche volume, and tree species diversity. Then, we test the relation between vertical canopy structure, as a proxy for vertical niche occupation, and tree species diversity. We use large footprint full-waveform airborne lidar data collected across four study sites in Gabon (Lopé, Mabounié, Mondah, and Rabi) in combination with in situ estimates of species richness (S) and Shannon diversity (H′). Linear models using canopy height explained 44% and 43% of the variation in S and H′ at the 0.25 ha resolution. Linear models using canopy height and the plant area volume density profile explained 71% of this variation. We demonstrate applications of these models by mapping S and H′ in Mondah using a simulated GEDI-TanDEM-X fusion height product, across the four sites using wall-to-wall airborne lidar data products, and across and between the study sites using ICESat lidar waveforms. The modeling results are encouraging in the context of developing pan-tropical structure diversity models applicable to data from current and upcoming spaceborne remote sensing missions

A computer-aided polyp detection system in screening and surveillance colonoscopy:an international, multicentre, randomised, tandem trial

Background: Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population. Methods: This multicentre, randomised, controlled trial was done in ten hospitals in Europe, the USA, and Israel by 31 endoscopists. Patients referred for non-immunochemical faecal occult blood test (iFOBT) screening or surveillance colonoscopy were included. Patients were randomomly assigned to CAD-assisted colonoscopy or conventional colonoscopy; a subset was further randomly assigned to undergo tandem colonoscopy: CAD followed by conventional colonoscopy or conventional colonoscopy followed by CAD. Primary objectives included adenoma per colonoscopy (APC) and adenoma per extraction (APE). Secondary objectives included adenoma miss rate (AMR) in the tandem colonoscopies. The study was registered at ClinicalTrials.gov, NCT04640792. Findings: A total of 916 patients were included in the modified intention-to-treat analysis: 449 in the CAD group and 467 in the conventional colonoscopy group. APC was higher with CAD compared with conventional colonoscopy (0·70 vs 0·51, p=0·015; 314 adenomas per 449 colonoscopies vs 238 adenomas per 467 colonoscopies; poisson effect ratio 1·372 [95% CI 1·068–1·769]), while showing non-inferiority of APE compared with conventional colonoscopy (0·59 vs 0·66; p&lt;0·001 for non-inferiority; 314 of 536 extractions vs 238 of 360 extractions). AMR in the 127 (61 with CAD first, 66 with conventional colonoscopy first) patients completing tandem colonoscopy was 19% (11 of 59 detected during the second pass) in the CAD first group and 36% (16 of 45 detected during the second pass) in the conventional colonoscopy first group (p=0·024). Interpretation: CAD increased adenoma detection in non-iFOBT screening and surveillance colonoscopies and reduced adenoma miss rates compared with conventional colonoscopy, without an increase in the resection of non-adenomatous lesions. Funding: Magentiq Eye.</p

Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage

Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H

Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

Objective To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia