Eosinophilic Esophagitis beyond Eosinophils - an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023.

Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis

Influence of iterative reconstruction on coronary calcium scores at multiple heart rates:A multivendor phantom study on state-of-the-art CT systems

The objective of this study was to evaluate the influence of iterative reconstruction on coronary calcium scores (CCS) at different heart rates for four state-of-the-art CT systems. Within an anthropomorphic chest phantom, artificial coronary arteries were translated in a water-filled compartment. The arteries contained three different calcifications with low (38 mg), medium (80 mg) and high (157 mg) mass. Linear velocities were applied, corresponding to heart rates of 0, < 60, 60-75 and > 75 bpm. Data were acquired on four state-of-the-art CT systems (CT1-CT4) with routinely used CCS protocols. Filtered back projection (FBP) and three increasing levels of iterative reconstruction (L1-L3) were used for reconstruction. CCS were quantified as Agatston score and mass score. An iterative reconstruction susceptibility (IRS) index was used to assess susceptibility of Agatston score (IRSAS) and mass score (IRSMS) to iterative reconstruction. IRS values were compared between CT systems and between calcification masses. For each heart rate, differences in CCS of iterative reconstructed images were evaluated with CCS of FBP images as reference, and indicated as small (< 5%), medium (5-10%) or large (> 10%). Statistical analysis was performed with repeated measures ANOVA tests. While subtle differences were found for Agatston scores of low mass calcification, medium and high mass calcifications showed increased CCS up to 77% with increasing heart rates. IRSAS of CT1-T4 were 17, 41, 130 and 22% higher than IRSMS. Not only were IRS significantly different between all CT systems, but also between calcification masses. Up to a fourfold increase in IRS was found for the low mass calcification in comparison with the high mass calcification. With increasing iterative reconstruction strength, maximum decreases of 21 and 13% for Agatston and mass score were found. In total, 21 large differences between Agatston scores from FBP and iterative reconstruction were found, while only five large differences were found between FBP and iterative reconstruction mass scores. Iterative reconstruction results in reduced CCS. The effect of iterative reconstruction on CCS is more prominent with low-density calcifications, high heart rates and increasing iterative reconstruction strength

Colonic Patch and colonic SILT development are independent and differentially-regulated events

Intestinal lymphoid tissues have to simultaneously ensure protection against pathogens and tolerance towards commensals. Despite such vital functions, their development in the colon is poorly understood. Here, we show that the two distinct lymphoid tissues of the colon–colonic patches and colonic SILTs–can easily be distinguished based on anatomical location, developmental timeframe and cellular organization. Furthermore, whereas colonic patch development depended on CXCL13-mediated LTi cell clustering followed by LTα-mediated consolidation, early LTi clustering at SILT anlagen did not require CXCL13, CCR6 or CXCR3. Subsequent dendritic cell recruitment to and gp38+VCAM-1+ lymphoid stromal cell differentiation within SILTs required LTα; B cell recruitment and follicular dendritic cell differentiation depended on MyD88-mediated signalling, but not the microflora. In conclusion, our data demonstrate that different mechanisms, mediated mainly by programmed stimuli, induce the formation of distinct colonic lymphoid tissues, therefore suggesting that these tissues may have different functions

A new approach to the assessment of lumen visibility of coronary artery stent at various heart rates using 64-slice MDCT

Coronary artery stent lumen visibility was assessed as a function of cardiac movement and temporal resolution with an automated objective method using an anthropomorphic moving heart phantom. Nine different coronary stents filled with contrast fluid and surrounded by fat were scanned using 64-slice multi-detector computed tomography (MDCT) at 50–100 beats/min with the moving heart phantom. Image quality was assessed by measuring in-stent CT attenuation and by a dedicated tool in the longitudinal and axial plane. Images were scored by CT attenuation and lumen visibility and compared with theoretical scoring to analyse the effect of multi-segment reconstruction (MSR). An average increase in CT attenuation of 144 ± 59 HU and average diminished lumen visibility of 29 ± 12% was observed at higher heart rates in both planes. A negative correlation between image quality and heart rate was non-significant for the majority of measurements (P > 0.06). No improvement of image quality was observed in using MSR. In conclusion, in-stent CT attenuation increases and lumen visibility decreases at increasing heart rate. Results obtained with the automated tool show similar behaviour compared with attenuation measurements. Cardiac movement during data acquisition causes approximately twice as much blurring compared with the influence of temporal resolution on image quality

Expression Patterns of TNFα, MAdCAM1, and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease.

Pathogenesis of cutaneous extraintestinal manifestations [EIM] in inflammatory bowel disease [IBD] remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics, such as anti-integrins or JAK-inhibitors, is not yet clear. We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, and Hsp-27/70 on 240 intestinal [55 controls, 185 IBD] and 64 skin biopsies [11 controls, 18 erythema nodosum [EN], 13 pyoderma gangenosum [PG], 22 psoriasis]. A semiquantitative score [0-100%] was used for evaluation. TNFα was upregulated in intestinal biopsies from active Crohn`s disease [CD] vs controls [36.2 vs 12.1, p &lt; 0.001], but not ulcerative colitis [UC: 17.9]. NFκB, however, was upregulated in intestinal biopsies from both active CD and UC [43.2 and 34.5 vs 21.8, p &lt; 0.001 and p = 0.017, respectively]. TNFα and NFκB were overexpressed in skin biopsies from EN, PG, and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, whereas it was upregulated in active UC vs controls [57.5 vs 35.4, p = 0.003]. STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, and a similar upregulation was seen in skin biopsies from EN [84.7 vs 22.3, p &lt; 0.001] and PG [60.5 vs 22.3, p = 0.011], but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls. Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1, support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab

Improved coronary calcium detection and quantification with low-dose full field-of-view photon-counting CT:a phantom study

OBJECTIVE: The aim of the current study was to systematically assess coronary artery calcium (CAC) detection and quantification for spectral photon-counting CT (SPCCT) in comparison to conventional CT and, in addition, to evaluate the possibility of radiation dose reduction. METHODS: Routine clinical CAC CT protocols were used for data acquisition and reconstruction of two CAC containing cylindrical inserts which were positioned within an anthropomorphic thorax phantom. In addition, data was acquired at 50% lower radiation dose by reducing tube current, and slice thickness was decreased. Calcifications were considered detectable when three adjacent voxels exceeded the CAC scoring threshold of 130 Hounsfield units (HU). Quantification of CAC (as volume and mass score) was assessed by comparison with known physical quantities. RESULTS: In comparison with CT, SPCCT detected 33% and 7% more calcifications for the small and large phantoms, respectively. At reduced radiation dose and reduced slice thickness, small phantom CAC detection increased by 108% and 150% for CT and SPCCT, respectively. For the large phantom size, noise levels interfered with CAC detection. Although comparable between CT and SPCCT, routine protocols CAC quantification showed large deviations (up to 134%) from physical CAC volume. At reduced radiation dose and slice thickness, physical volume overestimations decreased to 96% and 72% for CT and SPCCT, respectively. In comparison with volume scores, mass score deviations from physical quantities were smaller. CONCLUSION: CAC detection on SPCCT is superior to CT, and was even preserved at a reduced radiation dose. Furthermore, SPCCT allows for improved physical volume estimation. KEY POINTS: • In comparison with conventional CT, increased coronary artery calcium detection (up to 156%) for spectral photon-counting CT was found, even at 50% radiation dose reduction. • Spectral photon-counting CT can more accurately measure physical volumes than conventional CT, especially at reduced slice thickness and for high-density coronary artery calcium. • For both conventional and spectral photon-counting CT, reduced slice thickness reconstructions result in more accurate physical mass approximation

Influence of heart rate on coronary calcium scores:A multi-manufacturer phantom study

To evaluate the influence of heart rate on coronary calcium scores (CCS) using a dynamic phantom on four high-end computed tomography (CT) systems from different manufacturers. Artificial coronary arteries were moved in an anthropomorphic chest phantom at linear velocities, corresponding to < 60, 60-75 and > 75 beats per minute (bpm). Data was acquired with routinely used clinical protocols for CCS on four high-end CT systems (CT1-CT4). CCS, quantified as Agatston and mass scores were compared to reference scores at < 60 bpm. Influence of heart rate was assessed for each system with the cardiac motion susceptibility (CMS) Index. At increased heart rates (> 75 bpm), Agatston scores of the low mass calcification were similar to the reference score, while Agatston scores of the medium and high mass calcification increased significantly up to 50% for all CT systems. Threefold CMS increases at > 75 bpm in comparison with < 60 bpm were shown. For medium and high mass calcifications, significant differences in CMS between CT systems were found. Heart rate substantially influences CCS for high-end CT systems of four major manufacturers, but CT systems differ in motion susceptibility. Follow-up CCS CT scans should be acquired on the same CT system and protocol, and preferably with comparable heart rates

Next Steps for Human-Computer Integration

Human-Computer Integration (HInt) is an emerging paradigm in which computational and human systems are closely interwoven. Integrating computers with the human body is not new. however, we believe that with rapid technological advancements, increasing real-world deployments, and growing ethical and societal implications, it is critical to identify an agenda for future research. We present a set of challenges for HInt research, formulated over the course of a five-day workshop consisting of 29 experts who have designed, deployed and studied HInt systems. This agenda aims to guide researchers in a structured way towards a more coordinated and conscientious future of human-computer integration

Feasibility of computed tomography based thermometry during interstitial laser heating in bovine liver

To assess the feasibility of computed tomography (CT) based thermometry during interstitial laser heating in the bovine liver. Four freshly exercised cylindrical blocks of bovine tissue were heated using a continuous laser of Nd:YAG (wavelength: 1064 nm, active length: 30 mm, power: 10-30 W). All tissues were imaged at least once before and 7 times during laser heating using CT and temperatures were simultaneously measured with 5 calibrated thermal sensors. The dependency of the average CT numbers as a function of temperature was analysed with regression analysis and a CT thermal sensitivity was derived. During laser heating, the growing hypodense area was observed around the laser source and that area showed an increase as a function of time. The formation of hypodense area was caused by declining in CT numbers at increasing temperatures. The regression analysis showed an inverse linear dependency between temperature and average CT number with -0.65 +/- 0.048 HU/A degrees C (R(2) = 0.75) for the range of 18-85A degrees C in bovine liver. The non-invasive CT based thermometry during interstitial laser heating is feasible in the bovine liver. CT based thermometry could be further developed and may be of potential use during clinical LITT of the liver