Using Automated Machine Learning to Predict Necessary Upcoming Therapy Changes in Patients With Psoriasis Vulgaris and Psoriatic Arthritis and Uncover New Influences on Disease Progression: Retrospective Study.

BACKGROUND: Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are complex, multifactorial diseases significantly impacting health and quality of life. Predicting treatment response and disease progression is crucial for optimizing therapeutic interventions, yet challenging. Automated machine learning (AutoML) technology shows promise for rapidly creating accurate predictive models based on patient features and treatment data. OBJECTIVE: This study aims to develop highly accurate machine learning (ML) models using AutoML to address key clinical questions for PsV and PsA patients, including predicting therapy changes, identifying reasons for therapy changes, and factors influencing skin lesion progression or an abnormal Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. METHODS: Clinical study data from 309 PsV and PsA patients were extensively prepared and analyzed using AutoML to build and select the most accurate predictive models for each variable of interest. RESULTS: Therapy change at 24 weeks follow-up was modeled using the extreme gradient boosted trees classifier with early stopping (area under the receiver operating characteristic curve [AUC] of 0.9078 and logarithmic loss [LogLoss] of 0.3955 for the holdout partition). Key influencing factors included the initial systemic therapeutic agent, the Classification Criteria for Psoriatic Arthritis score at baseline, and changes in quality of life. An average blender incorporating three models (gradient boosted trees classifier, ExtraTrees classifier, and Eureqa generalized additive model classifier) with an AUC of 0.8750 and LogLoss of 0.4603 was used to predict therapy changes for 2 hypothetical patients, highlighting the significance of these factors. Treatments such as methotrexate or specific biologicals showed a lower propensity for change. An average blender of a random forest classifier, an extreme gradient boosted trees classifier, and a Eureqa classifier (AUC of 0.9241 and LogLoss of 0.4498) was used to estimate PASI (Psoriasis Area and Severity Index) change after 24 weeks. Primary predictors included the initial PASI score, change in pruritus levels, and change in therapy. A lower initial PASI score and consistently low pruritus were associated with better outcomes. BASDAI classification at onset was analyzed using an average blender of a Eureqa generalized additive model classifier, an extreme gradient boosted trees classifier with early stopping, and a dropout additive regression trees classifier with an AUC of 0.8274 and LogLoss of 0.5037. Influential factors included initial pain, disease activity, and Hospital Anxiety and Depression Scale scores for depression and anxiety. Increased pain, disease activity, and psychological distress generally led to higher BASDAI scores. CONCLUSIONS: The practical implications of these models for clinical decision-making in PsV and PsA can guide early investigation and treatment, contributing to improved patient outcomes.

Reduction of ADC bias in diffusion MRI with deep learning-based acceleration: A phantom validation study at 3.0 T.

PURPOSE: Further acceleration of DWI in diagnostic radiology is desired but challenging mainly due to low SNR in high b-value images and associated bias in quantitative ADC values. Deep learning-based reconstruction and denoising may provide a solution to address this challenge. METHODS: The effects of SNR reduction on ADC bias and variability were investigated using a commercial diffusion phantom and numerical simulations. In the phantom, performance of different reconstruction methods, including conventional parallel (SENSE) imaging, compressed sensing (C-SENSE), and compressed SENSE acceleration with an artificial intelligence deep learning-based technique (C-SENSE AI), was compared at different acceleration factors and flip angles using ROI-based analysis. ADC bias was assessed by Lin's Concordance correlation coefficient (CCC) followed by bootstrapping to calculate confidence intervals (CI). ADC random measurement error (RME) was assessed by the mean coefficient of variation (CV¯) and non-parametric statistical tests. RESULTS: The simulations predicted increasingly negative bias and loss of precision towards lower SNR. These effects were confirmed in phantom measurements of increasing acceleration, for which CCC decreased from 0.947 to 0.279 and CV¯ increased from 0.043 to 0.439, and of decreasing flip angle, for which CCC decreased from 0.990 to 0.063 and CV¯ increased from 0.037 to 0.508. At high acceleration and low flip angle, C-SENSE AI reconstruction yielded best denoised ADC maps. For the lowest investigated flip angle, CCC = {0.630, 0.771 and 0.987} and CV¯={0.508, 0.426 and 0.254} were obtained for {SENSE, C-SENSE, C-SENSE AI}, the improvement by C-SENSE AI being significant as compared to the other methods (CV: p = 0.033 for C-SENSE AI vs. C-SENSE and p < 0.001 for C-SENSE AI vs. SENSE; CCC: non-overlapping CI between reconstruction methods). For the highest investigated acceleration factor, CCC = {0.479,0.926,0.960} and CV¯={0.519,0.119,0.118} were found, confirming the reduction of bias and RME by C-SENSE AI as compared to C-SENSE (by trend) and to SENSE (CV: p < 0.001; CCC: non-overlapping CI). CONCLUSION: ADC bias and random measurement error in DWI at low SNR, typically associated with scan acceleration, can be effectively reduced by deep-learning based C-SENSE AI reconstruction.

Targeted multiparametric magnetic resonance imaging/transrectal ultrasound-guided (mpMRI/TRUS) fusion prostate biopsy versus systematic random prostate biopsy: A comparative real-life study.

BACKGROUND: Patients with suspected prostate cancer usually undergo transrectal ultrasound-guided (TRUS) systematic biopsy, which can miss relevant prostate cancers and lead to overtreatment. AIMS: The aim of this study was to evaluate the detection rate for prostate cancer in MR-guided targeted biopsy (TB) and systematic biopsy (SB) in comparison with mpMRI of the prostate. METHODS AND RESULTS: Three hundred and eight men who underwent mpMRI due to elevated PSA values between 2015 and 2020 were studied at university hospital Aachen, Germany. MRI-images were divided into cohorts with suspicious findings (PI-RADS ≥ 3) and negative findings (PI-RADS < 3). In patients with PI-RADS ≥ 3 TB combined with SB was performed. A part of this group underwent RP subsequently. In patients with PI-RADS < 3 and clinical suspicion SB was performed. In the PI-RADS ≥ 3 group (n = 197), TB combined with SB was performed in 194 cases. Three cases were lost to follow-up. Biopsy yielded 143 positive biopsies and 51 cases without carcinoma. TB detected 71% (102/143) and SB 98% (140/143) of the overall 143 carcinoma. Overall, 102 carcinomas were detected by TB, hereof 66% (67/102) clinically significant (Gleason ≥ 3+4) and 34% (35/102) clinically insignificant carcinoma (Gleason 3+3). SB detected 140 carcinomas, hereof 64% (90/140) csPCA and 36% (50/140) nsPCA. Forty-one of the overall 143 detected carcinoma were only found by SB, hereof 46% (19/41) csPCA and 54% (22/41) nsPCA. Tumor locations overlapped in 44% (63/143) between TB and SB. In 25% (36/143), SB detected additional tumor foci outside the target lesions. 70/143 patients subsequently underwent RP. The detection of tumor foci was congruent between mpMRI and prostatectomy specimen in 79% (55/70) of cases. Tumor foci were mpMRI occult in 21% (15/70) of cases. In the group with negative mpMRI (n = 111), biopsy was performed in 81 cases. Gleason ≥ 3+4 carcinoma was detected in 7% and Gleason 3+3 in 24% cases. CONCLUSION: There was a notable number of cases in which SB detected tumor foci that were mpMRI occult and could have been missed by TB alone. Therefore, additional systematic random biopsy is still required. A supplemental random biopsy should be considered depending on the overall clinical suspicion in negative mpMRI.

Response of broiler breeder pullets when fed hydrolyzed whole yeast from placement to 22 wk of age.

The study examined the effects of feeding broiler breeder pullets hydrolyzed whole yeast (HY) from hatch to 22 wk of age (WOA). A total of 524-day-old Ross 708 pullets were placed in floor pens (∼24 birds/pen) for the starter (0-4 WOA) and grower (5-18 WOA) phases, then transferred to the egg production facility and redistributed to ∼20 birds/pen for the prelay phase (19-22 WOA). Two diets were allocated to pens (0-18 WOA; n = 11) and (19-22 WOA; n-12). The diets were a control corn and soybean meal diet formulated to meet specifications and control plus 0.05% HY (HY). Birds had ad libitum access to feed in the first week and daily feed allocation based on pen BW from 2 WOA. Birds had free access to water throughout the trial. Body weight (BW) and uniformity (BW CV) were monitored. Boosters for infectious bronchitis and New Castle disease vaccines were administered at 18 WOA, and samples of pullets bled for antibody titer 5-day later. One pullet/pen was randomly selected, weighed, bled for plasma biochemistry, and necropsied for organ weights, ceca digesta for short-chain fatty acids (SCFA), and leg bones morphometry. In the starter and grower phases, birds fed HY were lighter and gained less (P < 0.05) than control birds. However, there were no diet effects (P > 0.05) on growth, the BW prelay phase, or BW uniformity throughout the trial. There were no (P > 0.05) diet effects on breast, gastrointestinal, liver and bursa weights, serum antibody titers, plasma biochemistry, SCFA and bone attributes. However, pullets fed HY had heavier (P = 0.047) spleen and tended to have lower (P = 0.080) plasma concentrations of aspartate aminotransferase (AST) relative to control pullets. In conclusion, the parameters assessed showed no negative consequences of feeding HY to broiler breeder pullets. However, effects on the spleen and plasma AST may indicate modest modulation of immunity and metabolism. The impact of the provision of HY during broiler breeder pullet phase on reproductive performance and chick quality should be investigated.

Encrypted federated learning for secure decentralized collaboration in cancer image analysis.

Artificial intelligence (AI) has a multitude of applications in cancer research and oncology. However, the training of AI systems is impeded by the limited availability of large datasets due to data protection requirements and other regulatory obstacles. Federated and swarm learning represent possible solutions to this problem by collaboratively training AI models while avoiding data transfer. However, in these decentralized methods, weight updates are still transferred to the aggregation server for merging the models. This leaves the possibility for a breach of data privacy, for example by model inversion or membership inference attacks by untrusted servers. Somewhat-homomorphically-encrypted federated learning (SHEFL) is a solution to this problem because only encrypted weights are transferred, and model updates are performed in the encrypted space. Here, we demonstrate the first successful implementation of SHEFL in a range of clinically relevant tasks in cancer image analysis on multicentric datasets in radiology and histopathology. We show that SHEFL enables the training of AI models which outperform locally trained models and perform on par with models which are centrally trained. In the future, SHEFL can enable multiple institutions to co-train AI models without forsaking data governance and without ever transmitting any decryptable data to untrusted servers.

Denoising diffusion probabilistic models for 3D medical image generation.

Recent advances in computer vision have shown promising results in image generation. Diffusion probabilistic models have generated realistic images from textual input, as demonstrated by DALL-E 2, Imagen, and Stable Diffusion. However, their use in medicine, where imaging data typically comprises three-dimensional volumes, has not been systematically evaluated. Synthetic images may play a crucial role in privacy-preserving artificial intelligence and can also be used to augment small datasets. We show that diffusion probabilistic models can synthesize high-quality medical data for magnetic resonance imaging (MRI) and computed tomography (CT). For quantitative evaluation, two radiologists rated the quality of the synthesized images regarding "realistic image appearance", "anatomical correctness", and "consistency between slices". Furthermore, we demonstrate that synthetic images can be used in self-supervised pre-training and improve the performance of breast segmentation models when data is scarce (Dice scores, 0.91 [without synthetic data], 0.95 [with synthetic data]).

Growth performance, nutrient digestibility, intestinal morphology, cecal mucosal cytokines and serum antioxidant responses of broiler chickens to dietary enzymatically treated yeast and coccidia challenge.

BACKGROUND: There is a growing search for natural feed additives to alleviate the deleterious effects of coccidia infection in poultry production. This study aimed to investigate the effect of enzymatically treated yeast (ETY) on the growth performance, nutrient digestibility, intestinal morphology, antioxidative status, and cecal mucosa cytokines of coccidia-challenged broiler chickens. METHODS: From d 1 to 14 post hatching, 480 broiler chickens were allocated to 3 corn-soybean meal-based experimental diets with increasing concentrations of ETY (0, 1, or 2 g/kg). The experiment was designed as a randomized complete block design with body weight (BW) used as a blocking factor. On d 14 post hatching, the birds were re-randomized within each of the 3 experimental diets. Each of the 3 diet groups was split into a challenge or no-challenge group. This resulted in a 3 × 2 factorial arrangement of treatments. The coccidia challenge was administered on d 15 by an oral gavage. RESULTS: Dietary ETY improved (P < 0.05) the G:F of birds on d 21 regardless of the challenge state and linearly increased (P < 0.01) the apparent ileal digestibility of dry matter (DM), nitrogen, and gross energy (GE). The coccidia challenge decreased (P < 0.05) BW gain and feed intake of broiler chickens and reduced (P < 0.01) the total tract retention of DM, GE, and nitrogen. The coccidia challenge increased (P < 0.01) the mRNA gene expression of TNFα, IL-1ß, IL-10, and IL-6 in the cecal mucosa. There was a tendency (P = 0.08) for ETY to linearly reduce IL-1ß expression. Additionally, ETY supplementation increased (P < 0.05) the gene expression of OCLN. Serum catalase increased (P < 0.05) with dietary ETY in broiler chickens on d 21. Dietary ETY linearly increased (P < 0.05) the ileal villus height to crypt depth ratio, and ileal goblet cell density in broiler chickens. The ileal and excreta oocyst counts decreased (P < 0.01) with increasing supplementation of dietary ETY in coccidia-challenged broiler chickens on d 21. CONCLUSIONS: Dietary ETY enhanced nutrient utilization and augmented intestinal development in broiler chickens. However, dietary ETY did not completely attenuate the adverse effects of a coccidia challenge in broiler chickens.

Egg production, egg quality, organ weight, bone ash, and plasma metabolites in 30-week-old Lohmann LSL lite hens fed corn and soybean meal-based diets supplemented with enzymatically treated yeast.

Highly prolific modern hens are susceptible to metabolic disorders that could be modulated by functional feedstuffs such as enzymatically treated yeast (ETY). Therefore, we assessed the dose-response of ETY on hen-day egg production (HDEP), egg quality attributes, organ weight, bone ash, and plasma metabolites in laying hens. A total of 160 thirty-week-old Lohmann LSL lite hens were placed in 40 enriched cages (4 birds/cage) based on body weight (BW) and allocated to 5 diets in a completely randomized design for a 12-wk trial. The diets were isocaloric and isonitrogenous corn and soybean meal based supplemented with 0.0, 0.025, 0.05, 0.1, or 0.2% ETY. Feed and water were provided ad libitum; HDEP and feed intake (FI) were monitored weekly, whereas egg components, eggshell breaking strength (ESBS), and thickness (EST) were monitored biweekly, and albumen IgA concentration was measured on wk 12. At the end of the trial, 2 birds/cage were bled for plasma and necropsied for liver, spleen, and bursa weight, ceca digesta for short chain fatty acids (SCFA) and tibia and femur for ash content. Supplemental ETY reduced HDEP quadratically (P = 0.03); the HDEP was 98, 98, 96, 95, and 94% for 0.0, 0.025, 0.05, 0.1, and 0.2% ETY, respectively. However, ETY linearly and quadratically (P = 0.01) increased egg weight (EW) and egg mass (EM). Specifically, EM was 57.9, 60.9, 59.9, 58.9, and 59.2 g/b for 0.0, 0.025, 0.05, 0.1, and 0.2% ETY, respectively. Egg albumen increased linearly (P = 0.01), and egg yolk decreased linearly (P = 0.03) in response to ETY. In response to ETY, the ESBS and plasma Ca increased linearly and quadratically (P ≤ 0.03). Plasma concentration of total protein and albumin increased quadratically (P ≤ 0.05) with ETY. Diets had no (P > 0.05) effects on FI, FCR, bone ash, SCFA, and IgA. In conclusion, 0.1% or higher ETY reduced egg production rate; however, linear improvement in EW and shell quality linked to larger albumen and higher plasma protein and Ca suggested modulation in protein and calcium metabolism.

Artificial Intelligence for Clinical Interpretation of Bedside Chest Radiographs.

Background Supine chest radiography for bedridden patients in intensive care units (ICUs) is one of the most frequently ordered imaging studies worldwide. Purpose To evaluate the diagnostic performance of a neural network-based model that is trained on structured semiquantitative radiologic reports of bedside chest radiographs. Materials and Methods For this retrospective single-center study, children and adults in the ICU of a university hospital who had been imaged using bedside chest radiography from January 2009 to December 2020 were reported by using a structured and itemized template. Ninety-eight radiologists rated the radiographs semiquantitatively for the severity of disease patterns. These data were used to train a neural network to identify cardiomegaly, pulmonary congestion, pleural effusion, pulmonary opacities, and atelectasis. A held-out internal test set (100 radiographs from 100 patients) that was assessed independently by an expert panel of six radiologists provided the ground truth. Individual assessments by each of these six radiologists, by two nonradiologist physicians in the ICU, and by the neural network were compared with the ground truth. Separately, the nonradiologist physicians assessed the images without and with preliminary readings provided by the neural network. The weighted Cohen κ coefficient was used to measure agreement between the readers and the ground truth. Results A total of 193 566 radiographs in 45 016 patients (mean age, 66 years ± 16 [SD]; 61% men) were included and divided into training (n = 122 294; 64%), validation (n = 31 243; 16%), and test (n = 40 029; 20%) sets. The neural network exhibited higher agreement with a majority vote of the expert panel (κ = 0.86) than each individual radiologist compared with the majority vote of the expert panel (κ = 0.81 to ≤0.84). When the neural network provided preliminary readings, the reports of the nonradiologist physicians improved considerably (aided vs unaided, κ = 0.87 vs 0.79, respectively; P < .001). Conclusion A neural network trained with structured semiquantitative bedside chest radiography reports allowed nonradiologist physicians improved interpretations compared with the consensus reading of expert radiologists. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Wielpütz in this issue.

Gastrointestinal dynamics, immune response, and nutrient digestibility of weanling pigs fed diets supplemented with enzymatically treated yeast1.

The objective of this trial was to investigate the effect of enzymatically treated yeast (ETY) on the growth performance, nutrient digestibility, immune response, and gut health of weanling pigs. A total of 192 weanling pigs (6.0 ± 1.04 kg) were allocated to 4 corn and soybean-based diets with increasing concentrations of ETY (0, 1, 2, or 4 g/kg) for a 43-d trial. There were 8 replicate pens (4 replicate pens per sex) and 6 pigs per replicate. The experiment was set up as a randomized complete block design with body weight used as a blocking factor. Pigs had ad libitum access to water and diets for the duration of the study. There was no effect of ETY supplementation on the growth performance indices of weanling pigs. At day 14, there was a quadratic decrease (P < 0.05) in the apparent total tract digestibility (ATTD) of acid detergent fiber (ADF). At day 28, there was a linear increase (P < 0.05) in the ATTD of neutral detergent fiber and a quadratic decrease (P < 0.05) in the ATTD of ADF. On day 14, there was a linear increase (P < 0.05) in serum catalase activity with ETY supplementation. There was a linear increase (P < 0.01) in the gene expression of glutathione peroxidase-4 in the ileal mucosa of pigs. Increasing dietary ETY supplementation linearly decreased (P < 0.05) the gene expression of ileal peptide transporter 1. There was a tendency for a quadratic effect (P = 0.07) in the ileal villus height to crypt depth ratio with ETY supplementation. In addition, there was a tendency for a linear increase (P = 0.06) in ileal digesta butyrate with ETY supplementation. In conclusion, the current study demonstrated that dietary ETY supplementation could partly ameliorate the deleterious effects of post-weaning stress by enhancing the antioxidative status of weanling pigs. However, prolonged supplementation of ETY may be needed to see its effect on growth performance.

The post-weaning stage is fraught with challenges that could affect piglet lifetime growth, development, and gut health. Various factors predispose pigs to stress after weaning. These factors include the separation of piglets from the sow, temperature changes, crowding stress, exposure to new animals, and dietary and environmental antigens. With the increased search for antibiotic alternatives in weanling pigs, identifying potential health-promoting feed additives is exigent. Enzymatically treated yeast (ETY) is rich in bioactive components, including immune-stimulating glucans, mannans, and peptides. These may confer beneficial effects on pigs during the post-weaning period. In this study, ETY was supplemented in graded levels in the diet of weanling pigs. Our results showed that dietary ETY supplementation influenced gut health by promoting a better antioxidant status in weanling pigs.

Enzymatically treated yeast bolstered growth performance of broiler chicks from young broiler breeders linked to improved indices of intestinal function, integrity, and immunity.

Older breeder chicks (OBC) are heavier and robust at hatch than younger breeder chicks (YBC). However, the implications of broiler breeder age on chick intestinal function and the role of functional feedstuffs are unexplored. We evaluated the effects of broiler breeder age and the impact of feeding YBC enzymatically treated yeast on growth, nutrient utilization, and indices of intestinal function. Fertile Ross 708 eggs: 2,250 (56.5 ± 3.4g) from 30-wk-old (YBC) and 550 (64.2 ± 4.2 g) from 47-wk-old (OBC) were hatched and placed in 48 pens (44 chicks/pen) containing equal males and females for growth and intestinal function evaluation and 36 cages (5 chicks/cage) for metabolizable energy (AME). Five corn and soybean meal-based diets were formulated to contain 0, 0.05, 0.10, 0.20, and 0.40% HY40 for a 3-phase feeding program (starter: days 0-10, grower: days 11-24, and finisher; days 25-42). Grower phase diets also contained a 0.3% TiO2 indigestible marker. The diets were allocated within YBC in a completely randomized block design (n = 8 for pens; n = 6 for cages). The OBC were fed a 0% yeast diet. Feed and water were provided freely; BW and feed intake were monitored, and excreta samples were collected on days 17 to 21 for apparent retention (AR). Birds were necropsied for plasma, jejunal tissues, organs weight, and ceca digesta. The OBC were heavier (P < 0.01) than YBC at hatch. Final BW of OBC and YBC fed, ≥0.10% yeast, was similar (P > 0.05). The OBC had similar FCR (P > 0.05) to YBC fed 0 to 0.10% yeast but higher (P = 0.003) than for YBC fed ≥0.20% yeast. Jejunal villi height to crypt depth ratio (VCR) and IgA were higher in OBC than 0% yeast (P = 0.01). Yeast increased VCR, bursa weight, jejunal, and plasma IgA (P = 0.01). The YBC fed ≥0.10% yeast had higher (P < 0.05) AR of crude protein, and gross energy than OBC and YBC fed 0 or 0.05% yeast. In conclusion, yeast improved YBC performance to the level of OBC linked to improved intestinal function, integrity, and immunity.

Bone Mineral Density Is a Predictor of Mortality in Female Patients with Cholangiocellular Carcinoma Undergoing Palliative Treatment.

BACKGROUND: Cholangiocellular adenocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts. Its general prognosis is poor as therapeutic options are limited. Many patients present with advanced stages of disease, and palliative chemotherapy remains the only treatment option. Prognostic markers to assess the outcome of chemotherapeutic treatment in CCA are limited. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients with advanced CCA. PATIENTS AND METHODS: We included 75 patients with advanced CCA that were treated at our academic tumor center. Prior to treatment, bone mineral density was analyzed at the first lumbar vertebra using routine CT scans in the venous phase and the local PACS (IntelliSpace PACS, Philips, Amsterdam, The Netherlands). RESULTS: BMD was not significantly different between male and female patients but decreased with age. Patients with BMD above 167 HU have a significantly improved overall survival (474 days vs. 254 days; log-rank X2(1) = 6.090; p = 0.014). The prognostic value of BMD was confirmed using univariate (HR 2.313 (95%CI: 1.170-4.575); p = 0.016) and multivariate (HR 4.143 (95%CI: 1.197-14.343); p = 0.025) Cox regression analyses. Subgroup analysis revealed that the prognostic value of BMD was only present in female patients and not in male patients, suggesting sex-specific differences. CONCLUSIONS: Our data suggest that BMD is a valuable, easily accessible, and independent prognostic marker for overall survival in patients with advanced CCA. Furthermore, subgroup analysis showed the sex specificity of this marker, which demonstrated relevance only in female patients.

Possible Alterations of Imaging Patterns in Computed Tomography for Delta-VOC of SARS-CoV-2.

BACKGROUND: So far, typical findings for COVID-19 in computed tomography (CT) have been described as bilateral, multifocal ground glass opacities (GGOs) and consolidations, as well as intralobular and interlobular septal thickening. On the contrary, round consolidations with the halo sign are considered uncommon and are typically found in fungal infections, such as invasive pulmonary aspergillosis. The authors recently observed several patients with COVID-19 pneumonia presenting with round, multifocal consolidations accompanied by a halo sign. As this may indicate alterations of CT morphology based on the virus variant, the aim of this study was to investigate this matter in more detail. METHODS: 161 CT scans of patients with confirmed SARS-CoV-2 infection (RT-PCR within 2 days of CT) examined between January 2021 and September 15, 2021 were included. Follow-up examinations, patients with invasive ventilation at the time of CT, and patients with insufficient virus typing for variants of concern (VOC) were excluded. CT scans were assessed for vertical and axial distribution of pulmonary patterns, degree of involvement, uni- vs. bilaterality, reticulations, and other common findings. The mean density of representative lesions was assessed in Hounsfield units. Results were compared using Mann-Whitney U-tests, Student's t-rests, descriptive statistics, and Fisher's exact tests. RESULTS: 75 patients did not meet the inclusion criteria. Therefore, 86/161 CT scans of unique patients were analyzed. PCR VOC testing confirmed manifestation of the Delta-VOC SARS-CoV-2 in 22 patients, 39 patients with Alpha-VOC and the remaining 25 patients with Non-VOC SARS-CoV-2 infections. Three patients with the Delta-VOC demonstrated multiple pulmonary masses or nodules with surrounding halo sign, whereas no patients with either Alpha-VOC (p = 0.043) or non-VOC (p = 0.095) demonstrated these findings. All three patients were admitted to normal wards and had no suspicion of a pulmonary co-infection. Patients with Delta-VOC were less likely to have ground glass opacities compared to Alpha-VOC (7/22 or 31.8 % vs. 4/39 or 10.3 %; p < 0.001), whereas a significant difference has not been observed between Delta-VOC and non-VOC (5/25 or 20 %; p = 0.348). The mean representative density of lesions did not show significant differences between the studied cohorts. CONCLUSION: In this study 3 out of 22 patients (13.6 %) with Delta-VOC presented with bilateral round pulmonary masses or nodules with surrounding halo signs, which has not been established as a notable imaging pattern in COVID-19 pneumonia yet. Compared to the other cohorts, a lesser percentage of patients with Delta-VOC presented with ground glass opacities. Based on these results Delta-VOC might cause a divergence in CT-morphologic phenotype. KEY POINTS: · Until recently, CT-morphologic signs of COVID-19 pneumonia have been presumed to be uncontroversially understood. Yet, recently the authors observed diverging pulmonary alterations in patients infected with Delta-VOC.. · These imaging alterations included round pulmonary masses or nodules with surrounding halo sign.. · These imaging alterations have not yet been established as typical for COVID-19 pneumonia, yet.. · Based on these results, Delta-VOC could impose a divergence of CT-morphologic phenotype.. CITATION FORMAT: · Yüksel C, Sähn M, Kleines M et al. Possible Alterations of Imaging Patterns in Computed Tomography for Delta-VOC of SARS-CoV-2 . Fortschr Röntgenstr 2022; 194: 1229 - 1241.

Effects of early feeding of enzymatically treated yeast on growth performance, organ weights, intestinal histomorphology, and ceca microbial metabolites in broiler chickens subjected to Eimeria challenge.

The study evaluated effects of early feeding of enzymatically treated yeast on growth performance and selected physiological responses in broiler chickens. A total of 480-day-old (male) Ross × Ross 708 broiler chicks were placed in 24 floor pens (20 birds per pen) and allocated to 2 diets (control vs. yeast) in a completely randomized block design (n = 12). Diets were formulated for a 5-phase feeding program: Pre-starter; d 0 to 6 Starter; d 7 to 15, Grower: d 16 to 28, Finisher 1; d 28 to 42 and Finisher 2; d 43 to 56. The yeast was applied in pre-starter and starter diets at 0.6 and 0.2%, respectively. Birds received a common diet from d 16 to 56. Feed intake (FI) and body weight (BW) were recorded by phase for calculation of BW gain (BWG) and FCR. On d 10, all birds received an oral dose of 25,000 E. acervullina and 5,000 E. maxima sporulated oocysts in 1 mL of sterile saline. On d 15 post-hatch, one bird per pen was sacrificed for organ weights (gizzard, small intestine, ceca, liver, spleen, liver, and bursa), jejunal tissues for histomorphology and ceca digesta for microbial activity. On d 56, one bird per pen was sacrificed for organs and breast weight. In pre-starter phase, yeast fed birds showed improved (P < 0.05) BWG and FCR than control fed birds. Combining pre-starter and starter phases, the FCR of yeast fed birds showed improved FCR (1.115 vs. 1.135; P < 0.05) than control. The overall BWG (d 0-56) was 3.920 and 3.962 kg/ bird and corresponding values for FCR were, 1.808 and 1.755, for the control and yeast, respectively. Diets had no (P > 0.05) effects on physiological responses evaluated on necropsied birds except that yeast birds had (P < 0.05) lighter bursa than control birds on d 15. The current data indicated that yeast could support growth in early life of broiler chickens, but these effects were not sustained after the transitioning birds to common grower and finisher diets.

Growth performance, immune status, gastrointestinal tract ecology, and function in nursery pigs fed enzymatically treated yeast without or with pharmacological levels of zinc.

Growth performance and physiological responses of nursery piglets when fed enzymatically treated yeast (HY40) and pharmacological ZnO alone or in combination were investigated. A total of 144 pigs (21 d old, BW 7.32 ± 0.55 kg) were placed in 36 pens (4 pigs/pen). Pigs were randomly assigned to one of four dietary treatments (n = 9): 1) control corn-wheat-soybean meal diet (control), 2) control + HY40 (HY40), 3) control + (ZnO) and 4) control + HY40 + ZnO (HY40+ZnO). Inclusion of HY40 and ZnO was 0.5% and 3,000 ppm in phase I (days 0 to 14), respectively, and halved in phase II (days 15 to 42). All diets contained 0.2% TiO2 for determination of apparent total tract digestibility (ATTD) of components. Body weight and feed disappearance were recorded weekly. One pig per pen was killed for organ weights, blood, and tissue samples on day 14. Except for phase II, when HY40 + ZnO pigs had greater average daily feed intake (P = 0.004) than all other treatments, there were no (P > 0.05) interactions between HY40 and ZnO on growth performance. Pigs fed HY40 or ZnO containing diets were heavier (P < 0.05) than pigs fed without by the end of the study. On day 14, pigs fed additives exhibited higher (P ≤ 0.009) ATTD of dry matter (DM) and gross energy (GE) than control pigs. On day 28, pigs fed control, HY40, and HY40 + ZnO had greater (P ≤ 0.022) ATTD of DM, crude protein, and GE than piglets fed ZnO only. Pigs fed HY40 + ZnO had lower ileal digesta Escherichia coli concentration (P < 0.05) than HY40 and control pigs. Ileal digesta of pigs fed ZnO diets had higher lactobacillus to E. coli ratio (1.44 vs. 1.20; P = 0.001), exhibited higher concentrations of acetic (P = 0.01) and butyric acid (P = 0.01) but lower lactic (P = 0.02) and total short chain fatty acids (P = 0.033) than pigs fed non-ZnO diets. Greater (P < 0.05) mRNA expression of nutrient transporters, tight junction proteins, and fecal excretion of zinc (Zn) was observed in ZnO pigs relative to non-ZnO pigs. Pigs fed HY40 diets had greater (P = 0.002) villus height to crypt depth ratio (VH:CD) than non-HY40 pigs. The concentration of plasma IgA was higher (P = 0.04) in HY40 + ZnO pigs relative to other pigs, whereas HY40 pigs showed higher (P < 0.001) jejunal IgA than non-HY40 pigs. Although the mode of action of HY40 and ZnO differed, the present study indicated that HY40 improved growth performance and jejunal function and immunity, making HY40 an effective alternative to pharmacological ZnO in nursery pigs feeding programs.

Abrupt weaning of pig results in nutritional, environmental, and psychological stresses leading to reduced feed intake, little or no weight gain and in some instances diarrhea, morbidity, and mortality. The post-weaning growth performance lag is often managed by use of antimicrobial growth promoters (AGP), pharmacological levels of trace elements such as zinc oxide (ZnO), specialty feed ingredients, and additives. However, many jurisdictions have already banned, and others are considering banning/restricting use of AGP to abate burgeoning levels of antimicrobial resistance in pathogens of animal and human. The European Union confirmed banning pharmacological ZnO effective June 2022 because of environmental pollution. In this context, identifying alternative nutritional strategies for managing newly weaned pigs is of global concern. Yeast derivatives have been proposed to be beneficial in transitioning piglets. However, there is little available information on comparative efficacy of yeast derivatives and pharmacological ZnO. The current study demonstrated that enzymatically treated yeast (HY40) had positive effects on growth, intestinal histomorphology, nutrient digestibility, and immune indices in nursery pigs. Through differing modes of action, overall growth performance of HY40 piglets was comparable to that of pharmacological ZnO piglets.

Reliability as a Precondition for Trust-Segmentation Reliability Analysis of Radiomic Features Improves Survival Prediction.

Machine learning results based on radiomic analysis are often not transferrable. A potential reason for this is the variability of radiomic features due to varying human made segmentations. Therefore, the aim of this study was to provide comprehensive inter-reader reliability analysis of radiomic features in five clinical image datasets and to assess the association of inter-reader reliability and survival prediction. In this study, we analyzed 4598 tumor segmentations in both computed tomography and magnetic resonance imaging data. We used a neural network to generate 100 additional segmentation outlines for each tumor and performed a reliability analysis of radiomic features. To prove clinical utility, we predicted patient survival based on all features and on the most reliable features. Survival prediction models for both computed tomography and magnetic resonance imaging datasets demonstrated less statistical spread and superior survival prediction when based on the most reliable features. Mean concordance indices were Cmean = 0.58 [most reliable] vs. Cmean = 0.56 [all] (p < 0.001, CT) and Cmean = 0.58 vs. Cmean = 0.57 (p = 0.23, MRI). Thus, preceding reliability analyses and selection of the most reliable radiomic features improves the underlying model's ability to predict patient survival across clinical imaging modalities and tumor entities.

Stent Graft Placement by Pseudoaneurysm of the Hepatic Arteries: Efficacy and Patency Rate in Follow-up.

PURPOSE: To investigate efficacy and patency status of stent graft implantation in the treatment of hepatic artery pseudoaneurysm. MATERIALS AND METHODS: A retrospective analysis of patients who had undergone endovascular treatment of hepatic artery pseudoaneurysms between 2011 and 2020 was performed. Medical records were examined to obtain patients' surgical histories and to screen for active bleeding. Angiographic data on vascular access, target vessel, material used and technical success, defined as the exclusion of the pseudoaneurysm by means of a stent graft with sufficient control of bleeding, were collected. Vessel patency at follow-up CT was analyzed and classified as short-term (< 6 weeks), mid-term (between 6 weeks and 1 year), and long-term patency (> 1 year). In case of stent occlusion, collateralization and signs of hepatic hypoperfusion were examined. RESULTS: In total, 30 patients were included and of these, 25 and 5 had undergone stent graft implantation and coiling, respectively. In patients with implanted stent grafts, technical success was achieved in 23/25 patients (92%). Follow-up CT scans were available in 16 patients, showing stent graft patency in 9/16 patients (56%). Short-term, mid-term, and long-term short-term stent patency was found in 81% (13/16), 40% (4/10), and 50% (2/4). In patients with stent graft occlusion, 86% (6/7) exhibited maintenance of arterial liver perfusion via collaterals and 14% (1/7) exhibited liver abscess during follow-up. CONCLUSION: Stent graft provides an effective treatment for hepatic artery pseudoaneurysms. Even though patency rates decreased as a function of time, stent occlusion was mainly asymptomatic due to sufficient collateralization.

Automated major psoas muscle volumetry in computed tomography using machine learning algorithms.

PURPOSE: The psoas major muscle (PMM) volume serves as an opportunistic imaging marker in cross-sectional imaging datasets for various clinical applications. Since manual segmentation is time consuming, two different automated segmentation methods, a generative adversarial network architecture (GAN) and a multi-atlas segmentation (MAS), as well as a combined approach of both, were investigated in terms of accuracy of automated volumetrics in given CT datasets. MATERIALS AND METHODS: The bilateral PMM was manually segmented by a radiologist in 34 abdominal CT scans, resulting in 68 single 3D muscle segmentations as training data. Three different methods were tested for their ability to generate automated image segmentations: a GAN- and MAS-based approach and a combined approach of both methods (COM). Bilateral PMM volume (PMMV) was calculated in cm3 by each algorithm for every CT. Results were compared to the corresponding ground truth using the Dice similarity coefficient (DSC), Spearman's correlation coefficient and Wilcoxon signed-rank test. RESULTS: Mean PMMV was 239 ± 7.0 cm3 and 308 ± 9.6 cm3, 306 ± 9.5 cm3 and 243 ± 7.3 cm3 for the CNN, MAS and COM, respectively. Compared to the ground truth the CNN and MAS overestimated the PMMV significantly (+ 28.9% and + 28.0%, p < 0.001), while results of the COM were quite accurate (+ 0.7%, p = 0.33). Spearman's correlation coefficients were 0.38, 0.62 and 0.73, and the DSCs were 0.75 [95%CI: 0.56-0.88], 0.73 [95%CI: 0.54-0.85] and 0.82 [95%CI: 0.65-0.90] for the CNN, MAS and COM, respectively. CONCLUSION: The combined approach was able to efficiently exploit the advantages of both methods (GAN and MAS), resulting in a significantly higher accuracy in PMMV predictions compared to the isolated implementations of both methods. Even with the relatively small set of training data, the segmentation accuracy of this hybrid approach was relatively close to that of the radiologist.

Sarcopenia Predicts Cancer Mortality in Male but Not in Female Patients Undergoing Surgery for Cholangiocellular Carcinoma.

INTRODUCTION: Surgery represents the only curative treatment option for patients with cholangiocarcinoma. However, complete tumor resection requires extensive surgery in many patients, and it is still debated which patients represent the ideal candidates for such therapy in terms of overall survival. Sarcopenia has been associated with an adverse outcome for various malignancies, but its role in the context of patients undergoing tumor resection for cholangiocellular adenocarcinoma (CCA) is only poorly understood. Here, we evaluated the role of sarcopenia in the outcome of CCA patients undergoing radical tumor resection. METHODS: Pre-operative CT scans were used to assess the skeletal muscle index (L3SMI) as well as the psoas muscle index (L3PMI) in n = 76 patients receiving curative intended surgery for CCA. L3SMI and L3PMI were correlated with clinical and laboratory markers. RESULTS: Patients with a skeletal muscle index or psoas muscle index above an established ideal cut-off (54.26 and 1.685 cm2/m2) showed a significantly better overall survival in Kaplan-Meier Curve analyses (L3SMI: 1814 days (95% CI: 520-3108) vs. 467 days (95% CI: 225-709) days; log rank X2(1) = 7.18, p = 0.007; L3PMI: 608 days (95% CI: 297-919) vs. 87 days (95% CI: 33-141), log rank X2(1) = 18.71; p < 0.001). Notably, these findings, especially for L3PMI, were confirmed in univariate (L3SMI: HR 0.962 (0.936-0.989); p = 0.006; L3PMI: HR 0.529 (0.366-0.766); p ≤ 0.001) and multivariate Cox regression analyses. Further analyses revealed that the prognostic value of both L3SMI and L3PMI was restricted to male patients, while in female patients survival was independent of the individual muscle mass. CONCLUSION: Measurement of muscle mass from preoperative CT scans represents an easily obtainable tool to estimate patient prognosis following curative surgery. The prognostic value was restricted to male patients, while in female patients these parameters did not reflect the patient outcome.

3D-Printed Replica and Porcine Explants for Pre-Clinical Optimization of Endoscopic Tumor Treatment by Magnetic Targeting.

BACKGROUND: Animal models have limitations in cancer research, especially regarding anatomy-specific questions. An example is the exact endoscopic placement of magnetic field traps for the targeting of therapeutic nanoparticles. Three-dimensional-printed human replicas may be used to overcome these pitfalls. METHODS: We developed a transparent method to fabricate a patient-specific replica, allowing for a broad scope of application. As an example, we then additively manufactured the relevant organs of a patient with locally advanced pancreatic ductal adenocarcinoma. We performed experimental design investigations for a magnetic field trap and explored the best fixation methods on an explanted porcine stomach wall. RESULTS: We describe in detail the eight-step development of a 3D replica from CT data. To guide further users in their decisions, a morphologic box was created. Endoscopies were performed on the replica and the resulting magnetic field was investigated. The best fixation method to hold the magnetic field traps stably in place was the fixation of loops at the stomach wall with endoscopic single-use clips. CONCLUSIONS: Using only open access software, the developed method may be used for a variety of cancer-related research questions. A detailed description of the workflow allows one to produce a 3D replica for research or training purposes at low costs.