Citations

AimThe aim of this study was to compare the histopathologic features of MMF‐induced colitis and colonic GVHD and develop a digital tool using deep learning convolutional neural networks (CNNs) to semi‐automate the quantification of eosinophils.MethodsMMF and GVHD colitis cases were retrieved. A cohort of transplant patients who were at risk for developing GVHD and were on MMF at the time of biopsy was also identified. Cases were reviewed for histologic features and a deep learning CNN was trained to quantify lamina propria eosinophils. Clinical history was collected.ResultsNinety‐five patients were included in the study group: GVHD (n = 37), MMF (n = 25) and GVHD vs. MMF (n = 33). Within the GVHD vs. MMF group, one patient was thought to have definitive MMF colitis and one possible MMF colitis. The GVHD group had a significantly higher apoptotic count compared to the MMF group (median: 7 vs. 2, P = 0.03). Neuroendocrine aggregates were present in the GVHD (N = 12) and GVHD vs. MMF (N = 4) groups while absent in the MMF group. The MMF group had a higher semi‐quantitative eosinophil score and a higher automated eosinophil count as detected by the deep learning CNN (median eos/HPF: MMF 19.2, GVHD vs. MMF 3.6, GVHD 3.4, P < 0.001).ConclusionsLower eosinophil counts, higher apoptotic counts and neuroendocrine cell aggregates favour the diagnosis of GVHD. AI models for eosinophil quantification may serve as an ancillary tool for assessing this differential diagnosis. Given the rarity of MMF‐induced colitis in SCT patients, pathologists should have a high threshold for making this diagnosis in this population.

AimsThere are no standardized histologic criteria for diagnosing serrated epithelial change (SEC) in inflammatory bowel disease (IBD), but two commonly used definitions are currently in use. The first definition (DEF1) is a simpler definition but requires endoscopic correlation. It encompasses all endoscopically invisible or non‐targeted serrated lesions without morphologic evidence of dysplasia that do not meet the diagnostic criteria of sessile serrated lesion (SSL) or traditional serrated adenoma (TSA). In contrast, the second definition (DEF2) incorporates more complex morphologic criteria (i.e., disorganized crypt architecture with some crypts no longer perpendicular or extending down to the muscularis mucosae, irregular serration spanning the entire thickness of the mucosa, and goblet cell‐rich epithelium), but does not necessitate endoscopic correlation. The reproducibility of SEC diagnoses using these definitions among gastrointestinal (GI) pathologists has not yet been evaluated.Methods and resultsSeven GI pathologists independently evaluated 38 GI cases, including 21 digitally scanned biopsy slides and 17 previously published images, demonstrating various types of serrated changes and their morphologic mimics. The diagnostic categories included: (1) SEC, (2) hyperplastic polyp (HP), (3) SSL, (4) TSA, (5) hypermucinous dysplasia (HMD), and (6) no serrated change or dysplasia (NSD). All cases were selected by a single pathologist (WTC) who did not participate in the interobserver study. The pathologists initially assessed each case as if it were endoscopically normal and provided a diagnosis using DEF1. Next, they re‐evaluated each case, this time considering it as a nodular or polypoid lesion, and again made a diagnosis using DEF1. The same process was then repeated for each case but using DEF2. A total of 532 diagnoses were made for each definition (7 pathologists × 38 cases × 2 endoscopic appearances). Fleiss' kappa statistics were used to assess the level of agreement among the seven pathologists. The total number of SEC diagnoses using DEF1 (n = 110 of 532) was more than twice that of DEF2 (n = 50 of 532). Also, the number of SEC diagnoses per pathologist was higher using DEF1 (mean: 16, range: 12–18) compared to DEF2 (mean: 7, range: 0–14). Furthermore, the instances where four or more pathologists agreed on the diagnosis of SEC were more frequent with DEF1 (16 of 38 cases) than with DEF2 (1 of 38 cases). The overall agreement in diagnosing SEC (vs. no SEC) using DEF1 was substantial (k = 0.69, P < 0.001), whereas the agreement using DEF2 was only slight (k = 0.18, P < 0.001). Among potential SEC mimics, there was substantial agreement in diagnosing HP (k = 0.69 using DEF1), SSL (k = 0.68), TSA (k = 1.00), HMD (k = 0.79), and NSD (k = 0.61) (P < 0.001).ConclusionsThe diagnosis of SEC using DEF1 is significantly more reproducible than using DEF2. Utilizing DEF1 is also less likely to miss potentially important cases of SEC. Therefore, DEF1 could be adopted to separate SEC from other serrated lesions and morphologic mimics in IBD.

ABSTRACTBackgroundPercutaneous transluminal angioplasty and stenting (PTAS) in patients with carotid stenosis may have potential effects on brain parenchyma. However, current studies on parenchymal changes are scarce due to the need for advanced imaging modalities. Consequently, the alterations in brain parenchyma following PTAS remain an unsolved issue.PurposeTo investigate changes to the brain parenchyma using magnetic resonance elastography (MRE).Study TypeProspective.Population13 patients (6 women and 7 men; 39 MRI imaging sessions) with severe unilateral carotid stenosis patients indicated for PTAS were recruited between 2021 and 2024.Field Strength/SequenceNoncontrast MRI sequences including MRE (spin echo) were acquired using 3 T scanners.AssessmentAll patients underwent MRE before (preprocedural), within 24 h (early postprocedural) and 3 months after (delayed postprocedural) PTAS. Preprocedural and delayed postprocedural ultrasonographic peak systolic velocity (PSV) was recorded. MRE stiffness and damping ratio were evaluated via neural network inversion of the whole brain, in 14 gray matter (GM) and 12 white matter (WM) regions.Statistical TestsStiffness and damping ratio differences between each pair of MR sessions for each subject were identified by paired sample t tests. The correlations of stiffness and damping ratio with stenosis grade and ultrasonographic PSV dynamics were evaluated by Pearson correlation coefficients. The statistical significance was defined as p < 0.05.ResultsThe stiffness of lesion side insula, deep GM, and deep WM increased significantly from preprocedural to delayed postprocedural MRE. Increasing deep GM stiffness on the lesion side was positively correlated with the DSA stenosis grade significantly (r = 0.609). The lesion side insula stiffness increments were positively correlated with PSV decrements significantly (r = 0.664).Data ConclusionRegional brain stiffness increased 3 months after PTAS. Lesion side stiffness was positively correlated with stenosis grades in deep GM and PSV decrements in the insula.Evidence Level2.Technical EfficacyStage 2.

Abstract Objectives To investigate socio-economic and clinical disparities in the utilisation of robotic surgery for head and neck cancer. Methods Using the National Cancer Database (2010–2020), 212 449 surgically treated patients were analysed. Multivariate logistic regression identified predictors of robotic versus non-robotic surgery ( p < 0.05). Results Robotic surgery utilisation increased over time during the study period. The following characteristics positively correlated with the use of robotic surgery: male, aged 41–80 years, White race, insured (with private insurance, Medicaid and Medicare) and treatment at an Academic/Research centre. Metropolitan residency, higher income/education levels, lower comorbidity (Charlson–Deyo score of 0) and Stage I disease were also associated with increased robotic surgery utilisation. Conclusion Significant socio-economic disparities exist in robotic surgery access, potentially exacerbating outcome inequities. Targeted interventions are needed to improve equity in treatment access and standardise care protocols. Further research should validate trends and address systemic barriers.

Background Balloon guide catheters (BGCs) are adjunctive devices that may be used during mechanical thrombectomy (MT) to induce flow arrest and improve clot retrieval and reperfusion outcomes for acute ischemic stroke. As the cost-effectiveness of BGC use remains uncertain, this study assessed short- and long-term direct healthcare costs associated with BGC use versus standard guide catheters (SGC) during MT. Methods A decision tree model estimated the short-term costs (index hospitalization), long-term costs (one year after index hospitalization), and total costs for patients undergoing MT + BGC versus MT + SGC from a healthcare system perspective in the United States (US), Canada, United Kingdom (UK), Sweden, Germany, Italy, Spain, Belgium, and The Netherlands. Average device costs were sourced from public tender prices and market research data. Weighted average healthcare costs for modified Rankin Scale scores were sourced from published literature for the respective countries. A 2024 meta-analysis supporting improved outcomes with BGC provided input parameters to model treatment effects for BGC and SGC. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of model parameters and accounted for uncertainty. Results Across all countries, long-term and total per-patient costs were lower with MT + BGC, yielding total per-patient cost savings of $6297 (US), CAD 3006 (Canada), £1828 (UK), 28,950 kr (Sweden), €1077 (Germany), €709 (Italy), €3678 (Spain), €2259 (Belgium), and €3344 (The Netherlands). The probability of MT + BGC yielding cost savings ranged 0.356–0.911 (short term), 0.962–0.975 (long term), and 0.838–0.935 (total costs). While long-term and total costs consistently favored MT + BGC, short-term cost savings showed more variability across countries. Conclusion This study demonstrates that BGC use is associated with total one-year per-patient cost savings for inpatient and postdischarge stroke care across the US, Canada, and seven European healthcare systems. Balloon guide catheters can potentially reduce post-stroke care costs and should be considered more broadly, despite the additional cost incurred by the device.

Artificial neural networks are now used across many fields, from medicine to chatbots. However, they are often complicated and give “black-box” predictions. To better understand these models, we outline some of the terminology, provide example applications in solid organ transplantation, and offer recommendations for those interested in starting to use such models. Examples and definitions are sourced from PubMed searches as well as a review of several applied texts in machine and deep learning. Neural networks have been applied in transplantation since the 1990s, but more recent applications involve their use to process nontabular data, such as images and text. Although interpretations of model results should take context into account, the power of these models holds great potential for the future in transplantation.

Abstract Front-line pharmaceutical interventions for treating acute graft-versus-host disease (GVHD) are not uniformly effective and have toxic side effects. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with potent in vitro and in vivo immunosuppressive functions. Clinical translation of in vitro–generated MDSCs has been limited because of requirements for multiple, high infusion doses, the relatively low yield from peripheral blood–sourced MDSCs (PB-MDSCs), and inconsistent product quality. To circumvent these obstacles, we developed a methodology to generate MDSCs using human induced pluripotent stem cell (iPSC)–derived CD34+ cells. Compared with PB-MDSCs, iPSC-derived MDSCs (iMDSCs) shared similar morphology, phenotype, and suppressive function. We found that the CD14+ iMDSC subset possessed the highest suppressor function. In previous studies, we reported that MDSCs transferred into mice with GVHD lost suppressor function because of inflammasome activation and immature myeloid cell maturation. In striking contrast to human PB-MDSCs, we show herein that iMDSCs retained 95% of suppressor function in vitro despite exposure to lipopolysaccharide (LPS) plus adenosine triphosphate (ATP), which are stimuli that activate the inflammasome via danger-associated molecular patterns released during early posttransplant conditioning and GVHD-induced injury. In an in vivo xenogenic GVHD model with PB mononuclear cells, iMDSCs significantly increased recipient survival without loss of antileukemia effects. iMDSC RNA sequencing and gene knockdown studies revealed that the maintenance of the purine metabolizing enzyme, phosphoglycerate dehydrogenase, during LPS plus ATP treatment, was linked to iMDSC inflammasome resistance. Taken together, these findings provide a platform for translating in vitro–generated, off-the-shelf iMDSCs into the clinic for suppressing a spectrum of adverse immune responses, including GVHD.

Background Eosinophilic oesophagitis (EoE) is a food allergen-induced inflammatory disorder characterised by interleukin (IL)-13-mediated oesophageal inflammation and epithelial basal cell hyperplasia (BCH). The role of mitochondria in EoE pathogenesis remains elusive. Design Prompted by single cell transcriptomics data, we interrogated the role of mitochondria in EoE pathobiology using patient biopsies, EoE-mouse models and oesophageal epithelial cells grown in monolayer and three-dimensional (3D) organoid cultures treated with EoE-relevant cytokines. 3D organoids and EoE-bearing mice were treated with omeprazole—a proton-pump inhibitor used as first-line EoE therapy. We performed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference in mouse organoids to identify the key mitochondrial regulatory genes whose depletion may lead to BCH. We analysed mitochondrial membrane potential, mass and superoxide production by flow cytometry, cellular oxygen consumption by respirometry, mitochondrial structures and perturbation of cellular energy homeostasis by immunoblotting. Results Mitochondrial dysfunction appeared to be a hallmark of EoE-related BCH where mitochondrial structural damage was associated with impaired oxidative respiratory capacity, elevation of mitochondrial superoxide and decreased adenosine triphosphate (ATP) production, as corroborated by activation of the adenosine monophosphate (AMP) -activated protein kinase and suppression of mammalian target-of-rapamycin signalling. Depletion of PGC1A, the master regulator of mitochondria biogenesis, recapitulated EoE-related BCH, suggesting that mitochondrial dysfunction drives BCH. Further, omeprazole alleviated mitochondrial damage and dysfunction in EoE-related BCH modelled in mice and patient-derived organoids. Conclusion Mitochondrial dysfunction is tightly linked to perturbation of redox homeostasis in EoE-related BCH, which is promoted by IL-13 and reversible with omeprazole treatment.