Analysis of Inflammatory Features in Suspicious Lesions for Significant Prostate Cancer on Magnetic Resonance Imaging-Are They Mimickers of Prostate Cancer?

Inflammation; Magnetic resonance imaging; Prostate cancerInflamació; Imatges per ressonància magnètica; Càncer de pròstataInflamación; Imágenes por resonancia magnética; Cáncer de próstataBackground. Inflammatory features can mimic PCa in suspicious MRI-lesions. Objectives: To assess the incidence of inflammatory features in targeted biopsies to suspicious lesions. Methods. A prospective analysis was conducted of 531 MRI-suspicious lesions with Prostate Imaging-Reporting and Data System (PI-RADS) scores of 3 to 5 in 364 men suspected of having PCa. Results. The incidence of inflammatory features in the MRI-suspicious lesions without PCa was 69.6%, compared to 48.1% in those with PCa (p < 0.001). Among the suspicious lesions without PCa, the incidence of inflammatory features ranged from 68.6% to 71.2% across the PI-RADS categories (p = 0.870). Mild chronic prostatitis increased with higher PI-RADS scores, while acute prostatitis decreased, and granulomatous prostatitis was exclusively observed in patients with PI-RADS scores of 4 and 5. The incidence of inflammatory features in the lesions with insignificant PCa (grade group 1) was 66.7%, compared to 42.7% in those with significant PCa (grade group 2 to 5; p = 0.027). The detection of inflammatory features in MRI-suspicious lesions was identified as an independent predictor of a lower likelihood of significant PCa detection, with an odds ratio (OR) of 0.326 (95% CI 0.196–0.541). Mild chronic prostatitis was the only type of prostatitis which was an independent predictor of a lower likelihood of significant PCa, with an OR of 0.398 (95% CI 0.268–0.590). Conclusions. These data suggest that inflammatory features may be considered mimickers of significant PCa on MRI.This research was funded by the Ministerio de Asuntos Económicos y Transformación Digital (SP) (MIA.2021.M02.0005) and the Instituto de Salut Carlos III (SP) (PI20/01666)

La hipercolesterolèmia [fullet]

Colesterol; Risc cardiovascular; HipercolesterolèmiaColesterol; Riesgo cardiovascular; HipercolesterolemiaCholesterol; Cardiovascular risk; HypercholesterolemiaInfografia sobre la hipercolesterolèmia, es detallen les recomanacions de tractament. Consells tant farmacològic, com tractament no farmacològic, dins de la campanya "Pastilles, només les necessàries".Infografía sobre la hipercolesterolemia, se detallan las recomendaciones de tratamiento. Consejos tanto farmacológico, como tratamiento no farmacológico, dentro de la campaña "Pastillas, sólo las necesarias".Infographic on hypercholesterolemia, treatment recommendations are detailed. Both pharmacological advice and non-pharmacological treatment, as part of the "Pills, only the necessary" campaign

Brentuximab vedotin compared with historical controls for severe skin involvement in cutaneous systemic sclerosis

Severe skin involvement; Cutaneous systemic sclerosisAfectació cutània; Esclerosi sistèmica cutàniaAfectación cutánea; Esclerosis sistémica cutáneaInvestigator-initiated study. Seagen provided partial funding and interpretation of the data. Seagen had courtesy access to the final manuscript, without having influence on the final publication

Clinical practice guidelines for the treatment of Ewing sarcoma (Spanish Sarcoma Research Group-GEIS)

Ewing sarcoma; Malignant bone tumours; Small round cell sarcomasSarcoma d'Ewing; Tumors ossis malignes; Sarcomes de cèl·lules rodones petitesSarcoma de Ewing; Tumores óseos malignos; Sarcomas de células redondas pequeñasEwing sarcoma is a small round-cell sarcoma characterized by gene fusion involving EWSR1 (or another TET family protein like FUS) and an ETS family transcription factor. The estimated incidence of this rare bone tumor, which occurs most frequently in adolescents and young adults, is 0.3 per 100,000/year. Although only 25% of patients with Ewing sarcoma are diagnosed with metastatic disease, historical series show that this is a systemic disease. Patient management requires multimodal therapies—including intensive chemotherapy—in addition to local treatments (surgery and/or radiotherapy). In the recurrent/refractory disease setting, different approaches involving systemic treatments and local therapies are also recommended as well as patient inclusion in clinical trials whenever possible. Because of the complexity of Ewing sarcoma diagnosis and treatment, it should be carried out in specialized centers and treatment plans should be designed upfront by a multidisciplinary tumor board. These guidelines provide recommendations for diagnosis, staging, and multimodal treatment of Ewing sarcoma

Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials

Risk stratification; Adult patients; T-cell acute lymphoblastic leukemiaEstratificació del risc; Pacients adults; Leucèmia limfoblàstica aguda de cèl·lules TEstratificación del riesgo; Pacientes adultos; Leucemia linfoblástica aguda de células TThis project was supported by the AECC (GC16173697BIGA); ISCIII (PI19/01828 and PI19/01183), co-funded by ERDF/ESF, “A way to make Europe”/”Investing in your future”, 2021 SGR 00560 (GRC)/CERCA Program/Generalitat de Catalunya. CG-G was supported by SEHH grant (2021). TL was supported by the Leukemia Stiftung (DJCLS 08 R/2022)

Treatment and Monitoring of Eosinophilic Fasciitis

Eosinophilic fasciitis; Groove sign; Immunosuppressive treatmentFascitis eosinofílica; Signo del surco; Tratamiento inmunosupresorFasciitis eosinofílica; Signe de solc; Tractament immunosupressorPurpose of Review Eosinophilic fasciitis (EF) is a rare inflammatory disease characterized by skin induration. Although some guidelines from scientific societies exist, standard recommendations on monitoring and therapy are lacking. Recent Findings Current therapy for patients diagnosed with EF includes glucocorticoids plus at least one immunosuppressive drug in cases of relapse or refractory disease. Methotrexate and mycophenolate mofetil are the most recommended, although recently a myriad of case reports or small series reporting the effectivity of biological agents or JAK inhibitors for treating relapses or refractory disease have been published. Anti-IL5 may have a role in those rare refractory cases with persistent eosinophilia. Intravenous immunoglobulins and photopheresis (in those centers with experience) may act as adjuvant therapies. Monitoring the disease activity is a cornerstone to ascertain if the treatment is useful or not. MRI, PET/TC, and more specifically POCUS have recently demonstrated their value for assessing therapy response. Summary High-quality data focused on therapy and monitoring is lacking in EF. Strategies for improving scientific quality of observational studies and consensus about “activity”, “sequela”, “relapse” or “refractoriness” terms in EF patients are necessary to implement prospective clinical trials and generate evidence-based medicine. Meanwhile we have to deal with the available information.Open Access Funding provided by Universitat Autonoma de Barcelona. Instituto de Salud Carlos III co-financed by the European Regional Development Fund (ERDF) PI22/00708. Grant recipient: Ernesto Trallero-Araguás and Albert Selva-O’Callaghan

L'abc de la calor: consells per a un estiu segur [cartell]

Calor; Consells; PrevencióCalor; Consejos; PrevenciónHeat; Tips; PreventionAquest cartell forma part de la campanya "L'ABC de la calor", que té com a objectiu conscienciar sobre els efectes de la calor i promoure mesures per prevenir-los, en un context en què les onades de calor són cada cop més habituals i freqüents.Este cartel forma parte de la campaña "L'ABC de la calor", que tiene como objetivo concienciar sobre los efectos del calor y promover medidas para prevenirlos, en un contexto en el que las olas de calor son cada vez más habituales y frecuentes.This poster is part of the campaign “L'ABC de la calor,” which aims to raise awareness about the effects of heat and promote measures to prevent them, in a context where heatwaves are increasingly common and frequent

Artificial intelligence-driven genotype–epigenotype–phenotype approaches to resolve challenges in syndrome diagnostics

Methylation; Splitting; Support vector machineMetilació; Divisió; Màquina de vectors de suportMetilación; División; Máquina de vectores de soporteBackground Decisions to split two or more phenotypic manifestations related to genetic variations within the same gene can be challenging, especially during the early stages of syndrome discovery. Genotype-based diagnostics with artificial intelligence (AI)-driven approaches using next-generation phenotyping (NGP) and DNA methylation (DNAm) can be utilized to expedite syndrome delineation within a single gene. Methods We utilized an expanded cohort of 56 patients (22 previously unpublished individuals) with truncating variants in the MN1 gene and attempted different methods to assess plausible strategies to objectively delineate phenotypic differences between the C-Terminal Truncation (CTT) and N-Terminal Truncation (NTT) groups. This involved transcriptomics analysis on available patient fibroblast samples and AI-assisted approaches, including a new statistical method of GestaltMatcher on facial photos and blood DNAm analysis using a support vector machine (SVM) model. Findings RNA-seq analysis was unable to show a significant difference in transcript expression despite our previous hypothesis that NTT variants would induce nonsense mediated decay. DNAm analysis on nine blood DNA samples revealed an episignature for the CTT group. In parallel, the new statistical method of GestaltMatcher objectively distinguished the CTT and NTT groups with a low requirement for cohort number. Validation of this approach was performed on syndromes with known DNAm signatures of SRCAP, SMARCA2 and ADNP to demonstrate the effectiveness of this approach. Interpretation We demonstrate the potential of using AI-based technologies to leverage genotype, phenotype and epigenetics data in facilitating splitting decisions in diagnosis of syndromes with minimal sample requirement.This work was supported by grants from the Society for the Relief of Disabled Children, Commissioned Paediatric Research at HKCH under The Health and Medical Research Fund (PR-HKU-4), the Agence Nationale de la Recherche “Investissements d’Avenir” program (ANR-10-IAHU-01), MSDAvenir (Devo-Decode project) and AXA (“Tête et Cœur” project). This work was supported by a Simons Foundation Autism Research Initiative (SFARI for RW) and an NSW Genomics Collaborative Grant (to AZ) and the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083091, Genetics Core). Bert Callewaert is a Senior Clinical Investigator of the Research Foundation – Flanders. E.B.O. was supported by the grant from Poznan University of Medical Sciences, Poland ProScience 2022 (502-14-11261860-11962). K.L. is supported by the National Institute for Health and Care Research Doctoral Research Fellowship 302303: The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. NIH P50HD103524 PI Sandra Juul, Genetics Core supported participant enrollment and clinical data collection for UW site. None of the sponsors had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Contribution of Blood Biomarkers to Multiple Sclerosis Diagnosis

Blood biomarkers; Multiple sclerosis diagnosisBiomarcadores sanguíneos; Diagnóstico; Esclerosis múltipleBiomarcadors sanguinis; Diagnòstic; Esclerosi múltipleBackground and Objectives Invasive procedures may delay the diagnostic process in multiple sclerosis (MS). We investigated the added value of serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), chitinase-3-like 1 (sCHI3L1), and the immune responses to the Epstein-Barr virus–encoded nuclear antigen 1 to current MS diagnostic criteria. Methods In this multicentric study, we selected patients from 2 prospective cohorts presenting a clinically isolated syndrome (CIS). Patients were classified as (1) not presenting dissemination in space (DIS) nor dissemination in time (DIT) (noDIS and noDIT); (2) presenting DIS without DIT (DIS and noDIT); and (3) presenting both (DIS and DIT), which were used as a reference. sNfL, sGFAP, and sCHI3L1 levels were measured with single-molecule array immunoassays and EBNA1-specific IgG levels with ELISA. Biomarker levels were compared between groups using linear regression models. Receiver operating characteristic curve analyses and Youden Index were used to determine cutoff values associated with MS diagnosis during follow-up. Results We included 181 patients (66.3% females, mean [SD] age of 35.0 [9.7] years). At baseline, 25 (13.8%) were classified as noDIS and noDIT, 62 (34.3%) as DIS and noDIT, and 94 (51.9%) as DIS and DIT. Only sNfL Z-scores discriminated between groups (DIS and DIT vs DIS and noDIT [p = 0.002], DIS and DIT vs noDIS and noDIT [p < 0.001], and DIS and noDIT vs noDIS and noDIT [p = 0.026]). In noDIS and noDIT patients (median interquartile range [IQR] follow-up of 8.1 [5.0–11.7] years), high sNfL Z-scores best predicted MS diagnosis (specificity [SP] and 95% CI of 93.3% [68.1–99.8] and positive predictive value [PPV] of 87.5% [47.3–99.7]). Among DIS and noDIT patients (median [IQR] follow-up of 6.8 [4.0–9.1] years), high sNfL Z-scores best predicted MS diagnosis (SP of 80% [28.4–99.5] and PPV of 97.3% [85.8–99.9]) without considering oligoclonal band (OB) status. In the subset of patients of this group with negative OBs, a combination of high sNfL Z-scores and sGFAP levels predicted MS diagnosis (SP of 100% [39.8–100] and PPV of 100% [54.1–100]). Discussion These results suggest that sNfL and sGFAP may be incorporated in particular scenarios to diagnose MS in patients with CIS not fulfilling current diagnostic criteria

TUXEDO-4: phase II study of trastuzumab-deruxtecan in HER2-low breast cancer with new or progressing brain metastases

Breast; Metastasis; Novel therapyMama; Metástasis; Terapia novedosaMama; Metàstasi; Teràpia novaBreast cancer (BC) is the most common cause of leptomeningeal disease (LMD) and the second most common cause of brain metastases (BMs) among all solid malignancies. Both BMs and LMD are associated with high morbidity and mortality and treatment options are limited. Trastuzumab deruxtecan (T-DXd), an antibody drug conjugate combining a HER2-targeting antibody with a topoisomerase I inhibitor, has shown activity in HER2-positive (HER2[+]) and HER2-low tumors in both preclinical and clinical settings. Similarly, T-DXd has shown efficacy in HER2[+] BC patients with central nervous system (CNS) involvement. However, data on activity in HER2-low BC patients with BMs and/or LMD using T-DXd are limited. TUXEDO-4 is an international, multicenter, single-arm, two-stage optimal Simon’s design, phase II trial (NCT06048718) that will recruit a total of 27 adult patients (13 in the first stage, and 14 in second stage depending on responses in the first stage) to evaluate T-DXd in the HER2-low metastatic BC population presenting with newly diagnosed or progressing BM with or without type II LMD. Clinical trial registration NCT06048718 (clinicaltrials.gov); 2023 -506,702-39–00 (EudraCT number).The TUXEDO-4 trial has been funded by Daiichi Sankyo, who has been involved in the decision to publish, and the preparation of the manuscript