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Mepolizumab versus benralizumab for eosinophilic granulomatosis with polyangiitis (EGPA): A European real-life retrospective comparative study
Get PDFBackground: Following the results of the MANDARA trial, this real-life study aimed at comparing the effectiveness and safety profile of mepolizumab versus benralizumab in a European EGPA cohort. Methods: We conducted a retrospective observational comparative study including EGPA patients, who received mepolizumab or benralizumab at the asthma dose. Patients were matched 1:1 by sex, age, BVAS and oral corticosteroid (OCS) dosage at the treatment initiation (T0). Complete response (CR) and partial response (PR), disease activity, OCS, pulmonary parameters, eosinophil count, relapses, and safety outcomes were also compared at 3, 6 and 12 months. Results: Patients treated with mepolizumab or benralizumab (n = 88 each) were matched: 57 % were females, median age was 54 years (IQR 45–60), median OCS dose 10 (7.5–12.5) and 10 (7–13) mg/day, median BVAS 4 (2–7) and 3 (2–8), respectively. 45.4 % of patients in the mepolizumab group and 51.1 % in the benralizumab group achieved CR or PR at T3, with CR steadily increasing during follow-up for both treatments. At T12, a higher CR rate was found in the benralizumab group (48.1 % vs 32.4 %, p = 0.005). No differences in BVAS, OCS, and respiratory parameters were observed between groups at the different timepoints. Throughout the follow-up, both treatments reduced eosinophil count, although a deeper reduction was found in the benralizumab group at all timepoints (p < 0.0001). Safety profile was comparable between patient groups. Conclusion: Mepolizumab and benralizumab showed comparable overall effectiveness and safety in EGPA. However, benralizumab achieved a higher CR rate at T12, and a deeper peripheral eosinophil reduction
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No full textWHU-RS19 ABZSL: An Attribute-Based Dataset for Remote Sensing Image Understanding
Get PDFThe advancement of artificial intelligence (AI) in remote sensing (RS) increasingly depends on datasets that offer rich and structured supervision beyond traditional scene-level labels. Although existing benchmarks for aerial scene classification have facilitated progress in this area, their reliance on single-class annotations restricts their application to more flexible, interpretable and generalisable learning frameworks. In this study, we introduce WHU-RS19 ABZSL: an attribute-based extension of the widely adopted WHU-RS19 dataset. This new version comprises 1005 high-resolution aerial images across 19 scene categories, each annotated with a vector of 38 features. These cover objects (e.g., roads and trees), geometric patterns (e.g., lines and curves) and dominant colours (e.g., green and blue), and are defined through expert-guided annotation protocols. To demonstrate the value of the dataset, we conduct baseline experiments using deep learning models that had been adapted for multi-label classification—ResNet18, VGG16, InceptionV3, EfficientNet and ViT-B/16—designed to capture the semantic complexity characteristic of real-world aerial scenes. The results, which are measured in terms of macro F1-score, range from 0.7385 for ResNet18 to 0.7608 for EfficientNet-B0. In particular, EfficientNet-B0 and ViT-B/16 are the top performers in terms of the overall macro F1-score and consistency across attributes, while all models show a consistent decline in performance for infrequent or visually ambiguous categories. This confirms that it is feasible to accurately predict semantic attributes in complex scenes. By enriching a standard benchmark with detailed, image-level semantic supervision, WHU-RS19 ABZSL supports a variety of downstream applications, including multi-label classification, explainable AI, semantic retrieval, and attribute-based ZSL. It thus provides a reusable, compact resource for advancing the semantic understanding of remote sensing and multimodal A
Seasonality and mortality in harbour benthic communities: the case of Leptogorgia sarmentosa (Octocorallia, Cnidaria) from a Mediterranean port
No full textHarbours are optimal sites for studying the effects of environmental fluctuations on benthic communities due to the wide variation in hydrological variables. The species living here also face trophic and spatial competition with non-indigenous species (NIS) carried into these areas by maritime traffic. Here we investigated temporal changes in biological, physical, and water quality variables affecting a shallow-water (0-20 cm) benthic assemblage found along a dock in the Port of Genoa (Ligurian Sea, NW Mediterranean Sea) with data obtained from long-term monitoring (August 2017 to November 2022). Visual surveys and quantitative samples indicated that this community is subjected to marked seasonal ecological changes. The assemblage includes persistent species and others with unpredictable peaks in abundance, partly due to competition with NIS. The abundance, size structure, and health status (i.e. percentage of colonies with epibionts) of the gorgonian Leptogorgia sarmentosa were used as early indicators of environmental stress. Sexual reproduction data were also gathered. Mortality events of various taxa, affecting juvenile or adult colonies, are linked to disturbances related to spring algal blooms, summer heat waves, and autumn heavy rainfall (reducing salinity, increasing the organic matter, and leading to hypoxic conditions). The strong resilience of L. sarmentosa, favoured by high settlement rates, is the key to the success of this species in harbour environments. This study represents a baseline for future monitoring of Mediterranean harbour benthic communities and offers the chance to better understand the functioning of marine ecosystems in relation to anthropogenic impacts and climate change scenarios
Static Visual Agnosia Following Awake Resection of a Left Frontal Low-Grade Glioma: A Case Report of Ventral Stream Network Disruption ("Astatopsia")
Get PDFBackground and Clinical Significance: Visual agnosia and speech production deficits are well-described sequelae of neurosurgical interventions, but their selective dissociation remains rare. This report presents an unusual combination of postoperative deficits following awake resection of a left frontal low-grade glioma. Case Presentation: We present the case of a right-handed female with left hemisphere language dominance who had a left frontal low-grade glioma. Preoperatively, she exhibited anomia and dysexecutive syndrome, including difficulty completing everyday goal-directed tasks such as sending emails and paying for parking. Following awake tumor resection, she developed two rare, dissociated deficits: (1) speech restricted to infinitive verb forms and (2) selective visual agnosia for static images, with preserved recognition of dynamic stimuli. Conclusions: This uncommon clinical constellation highlights the vulnerability of left frontal language and ventral visual processing networks during surgery and supports the dual-stream model of vision and language production. We describe a selective form of static visual agnosia affecting static images with relative preservation of dynamic and object recognition, for which we use the descriptive label “astatopsia”. This peculiar clinical condition is rarely documented in this particular combination and has not, to the best of our knowledge, previously been denominated in such a manner in the literature
Management of posterior cruciate ligament injuries: an expert consensus from 17 countries
Get PDFBACKGROUND: Posterior cruciate ligament (PCL) injury is a relatively common musculoskeletal condition. However, there is currently a lack of consensus on decision-making, treatment and postoperative management for such injuries. OBJECTIVES: To use the modified Delphi method to reach expert consensus on the management of PCL injury. METHODS: A literature search of PubMed, Cochrane Library, Embase, and Web of Science for articles up to 17 October 2024, to support the development of recommendation statements. An Expert Panel of 90 experienced clinicians from orthopedics and sports medicine participated in a two-round Delphi process. Each statement was evaluated in two parts: the first part assessed content appropriateness (score of 7-9 indicating appropriateness and 4-6 indicating possible appropriateness), while the second part assessed agreement (score of 5-9 indicating agreement). RESULTS: The panel members developed 11 statements using the Delphi process, addressing the following topics: (1) clinical decision-making, (2) treatment, and (3) postoperative management about PCL injuries. The final consensus was reached on 11 statements and we eventually translated these statements into a corresponding table of expert recommendations. CONCLUSION: Consensus was reached on 11 statements regarding three aspects of PCL injury management. These findings provide a foundation for developing evidence-based guidelines that can enhance clinical decision-making, improve treatment strategies, and optimize postoperative care for patients with PCL injuries
Continous or fixedcarfilzomib, lenalidomide and dexamethasone (krd) for relapsed-refractory multiple myeloma: long-term follow-up from a multicenter, retrospective real-life surveyfrom European myeloma network (emn) Italy
Get PDFBased on the results of the ASPIRE trial, the KRd regimen (carfilzomib, lenalidomide and dexamethasone) has been approved in Italy for relapsed/refractory multiple myeloma (RRMM) patients since 2016. The published KRd schedule indicates this combination for 18 cycles, followed by continuous Rd until progression. However, in Italy, there are no limits to the number of KRd cycles, fully refunded based on negotiation with the Italian regulatory agency, and in some centers this combination has been used continuously, beyond the 18th cycle (continuous KRd, cKRd). To evaluate and compare safety and efficacy of both continuous and fixed KRd, we retrospectively collected real-world data from 356 patients treated in 20 EMN (European Myeloma Network) Italian centers from October 2016 to September 2023 and we patients treated with cKRd with those treated with the ASPIRE schedule. After a median follow-up of 48.59 months (CI 27.24–61.24), the overall response rate (ORR) of the entire series was 83% with 35% of complete responses(CR). The mPFS was 23.1 months (CI 20.11–28.62) and mOS was 62.85 months (CI 53.75–70.34), longer than the mOS of the ASPIRE study (48.3 months). The landmark analysis of the cKRd population shows non-significant benefit both in terms of PFS and OS compared to patients where the administration of KRd was stopped at the 18th cycle as in the ASPIRE trial, to note, in the cKRd group patients had a more aggressive disease based on ISS and R-ISS stage. Therefore, although we did not observe additional toxicities, our retrospective analysis, while confirming the validity of the KRd regimen in RRMM, does not indicate any general advantage in keeping the administration of carfilzomib beyond the ASPIRE schedule
Anti-atherogenic immune checkpoint TIM-3 as a promising pharmacologic target toward ischemic heart diseases: a prospective review
No full textRecently, immunogene therapy has been of great interest in cardiovascular diseases. In this regard, various immune checkpoint inhibitors (ICIs) are identified to have a crucial role in regulating inflammatory responses. The T-cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3, CD366), a relatively newly discovered group of molecules with a conserved structure, has emerged as a critical immune checkpoint with significant regulatory roles in cardiovascular inflammation and atherosclerosis. This prospective review explores the importance of TIM-3 in modulating immune responses relevant to ischemic heart diseases (IHD), highlighting its interactions with inflammatory pathways such as Toll-like receptor-4 (TLR-4). TIM-3, predominantly expressed on T cells, dendritic cells, and monocytes, acts as an inhibitory receptor that quenches pro-inflammatory signaling, particularly upon binding to ligands like galectin-9. Noteworthy, recent evidence suggests that TIM-3 deficiency or dysregulation can exacerbate inflammatory cascades, contributing to the progression of IHD and related complications. Here, the therapeutic potential of targeting TIM-3 for the management of IHD, especially in the settings of systemic inflammation and post-operative complications, has been discussed. By elucidating the molecular mechanisms and translational prospects of TIM-3 modulation, this work proposes new avenues for immunotherapeutic intervention in cardiovascular disease and post-operative SIRS, warranting further research in clinical trials
Possible Eye Disorders in Children Prenatally Exposed to Either Methadone or Buprenorphine in Comparison with Other Medications; An Examination of the Food and Drug Administration (FDA) Pharmacovigilance Database
Get PDFBackground/Objectives: Recent studies have identified some concerns related to the occurrence of eye disorders in offspring of opioid-prescribed mothers, and especially so in those exposed to methadone. The aim here was to investigate, from a pharmacovigilance point of view, the association between opioid exposure during pregnancy and reported eye disorders in children. Methods: The FDA Adverse Event Reporting System (FAERS) was searched for the following: reports of eye disorders in children aged 0–17 years exposed during pregnancy to either methadone or buprenorphine; top 20 medications administered during pregnancy and associated with eventual occurrence of eye disorders in children; and reports of eye disorders in children from mothers prescribed with a range of psychotropics. Results: For 190 methadone and 79 buprenorphine cases, occurrence of eye disorders was registered as the consequence of having been exposed to these drugs in utero. After data cleaning, residual cases for methadone and buprenorphine were 17 and 15, respectively. Overall, in comparing the odds of eye disorders given methadone exposure to the odds of eye disorders given buprenorphine exposure, which represents a relative Reporting Odds Ratio (ROR) between two drugs, the relative ROR between methadone and buprenorphine was 0.59, suggesting lower odds of eye disorders for methadone compared to buprenorphine in children 0–17 years old antenatally exposed to either methadone or buprenorphine. Conversely, the ROR values resulting from a comparison of methadone- or buprenorphine-related data versus all other psychotropic drugs resulted in 0.27 (95% CI 0.16–0.48) and 0.47 (95% CI 0.26–0.85), respectively, indicating lower reporting odds of eye disorders for these molecules versus the pooled non-opioid comparator group. Medications prescribed during pregnancy which were most frequently related to the occurrence of eye disorders included the following: dupilumab (126 reports), valproate (69 reports), and ibuprofen (52 reports). Indeed, no opiates/opioids appeared among the top 20 drugs linked to eye disorders. A total of 25 and 11 unique cases were associated either with benzodiazepines or antipsychotics, respectively. Conclusions: No potential disproportionality safety signal for eye disorders associated with prenatal opioid exposure was identified. Specifically, the relative ROR indicated lower reporting odds for methadone compared to buprenorphine. The interpretation of these results is complicated by common co-exposures, polydrug interventions, and underlying maternal comorbidities, which introduce substantial confounding in real-world pharmacovigilance data. Overall, these findings highlight the importance of continued systematic post-marketing surveillance