Automated Detection and Segmentation of Nonmass-Enhancing Breast Tumors with Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Nonmass-enhancing (NME) lesions constitute a diagnostic challenge in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast. Computer-aided diagnosis (CAD) systems provide physicians with advanced tools for analysis, assessment, and evaluation that have a significant impact on the diagnostic performance. Here, we propose a new approach to address the challenge of NME lesion detection and segmentation, taking advantage of independent component analysis (ICA) to extract data-driven dynamic lesion characterizations. A set of independent sources was obtained from the DCE-MRI dataset of breast cancer patients, and the dynamic behavior of the different tissues was described by multiple dynamic curves, together with a set of eigenimages describing the scores for each voxel. A new test image is projected onto the independent source space using the unmixing matrix, and each voxel is classified by a support vector machine (SVM) that has already been trained with manually delineated data. A solution to the high false-positive rate problem is proposed by controlling the SVM hyperplane location, outperforming previously published approaches.European Unions Horizon 2020 Research and Innovation Programme under the Marie Skodowska-Curie grant agreement No. 656886Austrian National Bank "Jubilaeumsfond" Project 162192020-Research and Innovation Framework Programme PHC-11-2015 667211-2Siemens AustriaNovomedGuerbet, FranceNIH/NCI Cancer Center Support Grant P30CA00874

differential tbxa2 receptor transcript stability is dependent on the c924t polymorphism

Abstract Background In order to better characterize the molecular mechanisms involved in processing mutated transcripts, we investigated the post-transcriptional role of the C924T polymorphism (rs4523) located in the 3′ region of the TBXA2R gene. Methods and Results Experiments of dose response with Actinomycin D on MEG-01 human cell line showed a significant decrease on cell viability that was more evident on cells treated for 24 h. In addition, we showed that treatments with 5–10 μM, 15 μM and 20 μM of actinomycin D reduced cell viability by 44%, 72% and 75%, respectively, compared to the control group. Conversely, the samples treated with 1 μM of actinomycin D did not show significant difference on cell viability as compared to the control group. Analysis of the steady state mRNA level of TBXA2R by qRT-PCR evidenced an increase in mRNA stability for the wild type (C) compared to the mutant (T) allele. Furthermore, the expression levels of TBXA2R on wild type (CC) and mutant type (TT) patients, based on C924T polymorphism, were analyzed. The wild type showed a higher expression of TBXA2 receptor also with two different degrees of glycosylation (55 and 64 kDa), when compared to the mutant. These observations correlated with platelet aggregation, which was reduced in TT, independently of the platelet aggregation stimuli. Conclusions The instability of the TBXA2R transcript and the lack of effect on platelet aggregation might suggest a protective role for the TBXA2R TT genotype against atherothrombosis and its complications in high-risk aspirin-treated patients

Virtual Non-Contrast Spectral CT in Renal Masses:Is It Time to Discard Conventional Unenhanced Phase?

Dual-layer Dual-Energy CT (dl-DECT) allows one to create virtual non-contrast (VNC) reconstructions from contrast-enhanced CT scans, with a consequent decrease of the radiation dose. This study aims to assess the reliability of VNC for the diagnostic evaluation of renal masses in comparison with true non-contrast (TNC) images. The study cohort included 100 renal masses in 40 patients who underwent dl-DECT between June and December 2021. Attenuation values and standard deviations were assessed through the drawing of regions of interest on TNC and VNC images reconstructed from corticomedullary and nephrographic phases. A Wilcoxon signed-rank test was performed in order to assess equivalence of data and Spearman’s Rho correlation coefficient to evaluate correlations between each parameter. The diagnostic accuracy of VNC was estimated through the performance of receiver operating characteristic (ROC) curve analysis. Differences between attenuation values were, respectively, 74%, 18%, 5% and 3% (TNC-VNCcort), and 74%, 15%, 9% and 2% (TNC-VNCneph). The Wilcoxon signed-rank test demonstrated the equivalence of attenuation values between the TNC and VNC images. The diagnostic performance of VNC images in the depiction of kidney simple cysts remains high compared to TNC (VNCcort-AUC: 0.896; VNCneph-AUC: 0.901, TNC-AUC: 0.903). In conclusion, quantitative analysis of attenuation values showed a strong agreement between VNC and TNC images in the evaluation of renal masses.</p

Nusinersen Induces Disease-Severity-Specific Neurometabolic Effects in Spinal Muscular Atrophy

Intrathecal delivery of Nusinersen-an antisense oligonucleotide that promotes survival motor neuron (SMN) protein induction-is an approved therapy for spinal muscular atrophy (SMA). Here, we employed nuclear magnetic resonance (NMR) spectroscopy to longitudinally characterize the unknown metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of SMA patients across disease severity. Modulation of amino acid metabolism is a common denominator of biochemical changes induced by Nusinersen, with distinct downstream metabolic effects according to disease severity. In severe SMA1 patients, Nusinersen stimulates energy-related glucose metabolism. In intermediate SMA2 patients, Nusinersen effects are also related to energy homeostasis but involve ketone body and fatty acid biosynthesis. In milder SMA3 patients, Nusinersen mainly modulates amino acid metabolism. Moreover, Nusinersen modifies the CSF metabolome of a more severe clinical group towards the profile of untreated SMA patients with milder disease. These findings reveal disease severity-specific neurometabolic signatures of Nusinersen treatment, suggesting a selective modulation of peripheral organ metabolism by this CNS-directed therapy in severe SMA patients

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN). Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment. Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis. Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity

Preliminary data revealing efficacy of Streptococcus salivarius K12 (SSK12) in Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome: A multicenter study from the AIDA Network PFAPA syndrome registry

Objective: To evaluate the potential role of Streptococcus salivarius K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction. Patients and methods: The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months. Results: The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p &lt; 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p &lt; 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p &lt; 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p &lt; 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p &lt; 0.001), oral aphthae (p &lt; 0.001) and cervical lymphadenopathy (p &lt; 0.001) significantly decreased following SSK12. Conclusion: SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome

Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score

Objective To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. Conclusion The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p &lt; 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p &lt; 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths