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Strategies to mitigate breast-related adverse events in patients with high-risk biochemically recurrent prostate cancer receiving enzalutamide monotherapy: perspectives and challenges
No full textBackground and objectiveEnzalutamide (Enza) is the only androgen receptor pathway inhibitor approved as monotherapy for high-risk biochemically recurrent prostate cancer. Breast-related adverse events (BRAEs) are common among patients treated with Enza monotherapy (Enza-Mono). We review relevant clinical trial data, including unpublished data, on measures to prevent BRAEs. Given the absence of data on mitigating strategies for Enza-associated BRAEs, we draw on pertinent prophylactic strategies used in studies of bicalutamide, a nonsteroidal antiandrogen with a similar mechanism of action. We critically discuss the clinical implications of such strategies to support decision-making in patients receiving Enza-Mono.MethodsWe searched PubMed for clinical trials on the safety of Enza-Mono, with a focus on BRAEs. We added relevant unpublished data from the EMBARK and ENACT trials. We also explored the literature and summarize prophylactic strategies for bicalutamide-induced BRAEs.Key findings and limitationsIn three trials involving 533 patients treated with Enza-Mono, Enza-Mono (160 mg/d) was commonly associated with gynecomastia (37–49%), breast pain or tenderness (14–26%), and/or nipple pain (15–30%). No prophylactic measures for BRAEs were protocol-specified in these studies. Previous studies with bicalutamide (150 mg/d) reported the benefits and relative tolerability of prophylactic radiation therapy and/or tamoxifen or prophylactic anastrozole to mitigate gynecomastia or breast pain.Conclusions and clinical implicationsGiven the absence of data on prophylactic strategies for Enza-associated BRAEs, findings from bicalutamide studies could be extrapolated to Enza-Mono. Prospective trials are needed to optimize prophylactic strategies for BRAEs with Enza-Mono
Spatiotemporal patterns of asthma in Bhutan: a Bayesian analysis
No full textAsthma is a chronic respiratory disorder requiring ongoing medical management. This ecological study investigated the spatial and temporal patterns of notification rates for asthma from clinic visits and hospital discharges and identified demographic, meteorological and environmental factors that drive asthma in Bhutan. Monthly numbers of asthma notifications from 2016 to 2022 were obtained from the Bhutan Ministry of Health. Climatic variables (rainfall, relative humidity, minimum and maximum temperature) were obtained from the National Centre for Hydrology and Meteorology, Bhutan. The Normalised Difference Vegetation Index (NDVI) and surface particulate matter (PM2.5) were extracted from open sources. A multivariable zero-inflated Poisson regression (ZIP) model was developed in a Bayesian framework to quantify the relationship between risk of asthma and sociodemographic and environmental correlates, while also identifying the underlying spatial structure of the data. There were 12 696 asthma notifications, with an annual average prevalence of 244/100 000 population between 2016 and 2022. In ZIP analysis, asthma notifications were 3.4 times (relative risk (RR)=3.39; 95% credible interval (CrI) 3.047 to 3.773) more likely in individuals aged >14 years than those aged ≤14 years, and 43% (RR=1.43; 95% CrI 36.5% to 49.2%) more likely for females than males. Asthma notification increased by 0.8% (RR=1.008, 95% CrI 0.2% to 1.5%) for every 10 cm increase in rainfall, and 1.7% (RR=1.017; 95% CrI 1.2% to 2.3%) for a 1°C increase in maximum temperature. An increase in one unit of NDVI and 10 µg/m PM2.5 was associated with 27.3% (RR=1.273; 95% CrI 8.7% to 49.2%), and 2.0% (RR=1.02; 95% CrI 1.0% to 4.0%) increase in asthma notification, respectively. The high-risk spatial clusters were identified in the south and southeastern regions of Bhutan, after accounting for covariates. Environmental risk factors and spatial clusters of asthma notifications were identified. Identification of spatial clusters and environmental risk factors can help develop targeted interventions that maximise impact of limited public health resources for controlling asthma in Bhutan. [Abstract copyright: © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
Retinal biomarkers for Alzheimer’s disease in the prodromal and preclinical population - The Deep and Frequent Phenotyping study
No full textBACKGROUND: Recent challenges for disease-modifying therapies for Alzheimer's disease (AD) highlighted the need for biomarkers in the prodromal and preclinical stages. The Deep and Frequent Phenotyping (DFP) study aims to identify biomarkers for use in proof-of-concept trials. The DFP combines established AD markers with experimental approaches, including multimodal retinal imaging. Here, we report the baseline retinal vascular characteristics from ultra-widefield retinal images and retinal thickness measurements from Optical Coherence Tomography (OCT). METHOD: Participants were recruited aged ≥60 years with prodromal AD and control participants in a 4:1 ratio. Retinal vascular parameters (RVPs) were extracted from OPTOS ultrawide-field (UWF) images. Fractal dimension (FD), width gradient (WG), width intercept (WI), and tortuosity (TORT) were measured using the VAMPIRE software. OCT images were segmented with Heidelberg Eye Explorer (Heyex) to acquire the Retinal and Retinal Nerve Fibre Layer (RNFL) thickness. Associations between RVPs and AD risk factors (Family History of Dementia (FHD) and ApoE4 carrier status) were analysed in R, with results reported as medians and interquartile ranges. RESULT: FHD (n = 40) demonstrated significantly higher FD (1.13 [1.12, 1.15] vs 1.15 [1.13, 1.15], p <0.01) arterial WI (122μm [110, 132] vs 111μm [102, 129], p <0.05) alongside a lower arterial WG (-3.28μm/mm [-3.87, -2.74] vs -2.90μm/mm [-3.28, -2.35], p <0.05) compared to those without FHD (n = 51). ApoE4 carriers (n = 11) exhibited reduced arteriolar (100μm [94, 115] vs. 115μm [105, 121], p <0.05) and venular (131μm [121, 142] vs. 152μm [136, 159], p <0.05) WI compared to non-carriers (n = 80). No significant associations (p >0.05) were seen between TORT and FHD or ApoE4 status. FHD (n = 41) displayed a trend towards RNFL thickening in the Nasal (77μm [69, 87] vs 82μm [75, 90], p = 0.09) and inferotemporal (137μm [124, 148] vs 149μm [127, 158], p = 0.095) regions, compared to those without FHD (n = 48). No significant trends at baseline were observed between retinal thickness and FHD or ApoE4 status. CONCLUSION: These findings suggest that Retinal vascular parameters from OCT and UWF images may serve as non-invasive biomarkers for AD risk, offering a scalable early detection and monitoring method. Future work will focus on longitudinal data to assess trends and their role in tracking disease progression.</p
SN 2019tsf: evidence for extended hydrogen-poor CSM in the three-peaked light curve of stripped envelope of a Type Ib supernova
No full textWe present multiband ATLAS and ZTF photometry for SN 2019tsf, a Type Ib stripped-envelope supernova (SESN). The slow spectral evolution could be associated with an uncommon explosion mechanism specific to this SN. Possible explanations include fallback accretion onto a compact remnant or a long-lived central engine, both of which could provide extended energy injection responsible for the late-time rebrightening and unusual spectral features. The rebrightening observations represent the latest photometric measurements of a multipeaked Type Ib SN. As late-time photometry and spectroscopy suggest no hydrogen, the potential circumstellar material (CSM) must be H-poor. The absence of a nebular phase and the lack of narrow emission lines in the late-time spectra (>142 days) of the SNe suggest that any CSM interaction is likely asymmetric and enveloped by the SN ejecta. However, an extended CSM structure is evident through a follow-up radio campaign with the Karl G. Jansky Very Large Array (VLA), indicating a source of bright optically thick radio emission at late times, which is highly unusual among H-poor SESNe. We attribute this phenomenology to an interaction of the supernova ejecta with asymmetric CSM, potentially disk-like, and we present several models that may explain the origin of this rare Type Ib supernova. We propose a warped disk model in which a tertiary companion—commonly present around massive stars—perturbs the progenitor’s CSM, producing density enhancements that may explain the observed multipeaked SN 2019tsf light curve. This SN 2019tsf is a unique SN Type Ib among the recently discovered class of SNe that undergo mass transfer at the moment of explosion
JWST detection of a carbon-dioxide-dominated gas coma surrounding interstellar object 3I/ATLAS
No full text3I/ATLAS is the third confirmed interstellar object to visit our solar system and only the second to display a clear coma. Infrared spectroscopy with the James Webb Space Telescope (JWST) provides the opportunity to measure its coma composition and determine the primary activity drivers. We report the first results from our JWST NIRSpec campaign for 3I/ATLAS, at an inbound heliocentric distance of rH = 3.32 au. The spectral images (spanning 0.6–5.3 μm) reveal a CO2-dominated coma, with enhanced outgassing in the sunward direction and the presence of H2O, CO, water ice, dust, and a tentative detection of OCS. The coma CO2/H2O mixing ratio of 7.6 ± 0.3 is among the highest ever observed in a comet, and is 4.5σ above the trend as a function of rH for long-period and Jupiter-family comets (excluding the outlier C/2016 R2). Our observations are compatible with an intrinsically CO2-rich nucleus, which may indicate that 3I/ATLAS contains ices exposed to higher levels of radiation than solar system comets or that it formed close to the CO2 ice line in its parent protoplanetary disk. A relatively low coma H2O gas abundance may also be implied, for example, due to inhibited heat penetration into the nucleus, which could suppress the H2O sublimation rate relative to CO2 and CO
Efficacy of a feed additive consisting of 6-phytase produced with Aspergillus oryzae DSM 33737 (HiPhorius™) for all poultry, all porcine species and all fin fish (DSM Nutritional Products Ltd)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of 6-phytase produced by the genetically modified strain Aspergillus oryzae DSM 33737 (HiPhorius™) as a zootechnical feed additive for all poultry, all porcine species and all fin fish. In a previous opinion, the FEEDAP Panel concluded that the additive is safe for the target species, consumers and the environment. The Panel also concluded that the additive is not a skin and eye irritant but should be considered as skin and respiratory sensitiser. The Panel concluded that the additive had the potential to be efficacious as a zootechnical additive when included in the diet of poultry for fattening or reared for laying/breeding, reproductive porcine species and all fin fish. However, due to the lack of sufficient data, the Panel was not in the position to conclude on the efficacy for laying and reproductive poultry and growing porcine species. The applicant provided new trials to support the efficacy of the additive in those target species. Based on the data provided in the previous and current applications, the Panel concluded that the additive has the potential to be efficacious in all poultry and all porcine species.</p
Assessment of the feed additive consisting of taurine (3a370) for Canidae, Felidae, Mustelidae and carnivorous fish for the renewal of its authorisation and the request for a new use in all poultry and all porcine species (Regal B. V.)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of taurine as a nutritional feed additive (functional group: vitamins, pro-vitamins and chemically well-defined substances having similar effect) for the renewal of its authorisation for use in Canidae, Felidae, Mustelidae and carnivorous fish and for the new use in the same category (functional group: amino acids, their salts and analogues), in all poultry and all porcine species. The FEEDAP Panel concludes that taurine remains safe under the current conditions of authorisation for Canidae, Felidae, Mustelidae and carnivorous fish, consumer and environment. The Panel also concludes that levels up to 0.2%, with no margin of safety, are tolerated in all poultry and all porcine species, for which the new use of taurine as an amino acid is requested. The FEEDAP Panel concludes that the additive is a skin and eye irritant, and a skin and respiratory sensitiser and that any exposure is considered a risk. There is no need for the assessment of the efficacy of the additive in Canidae, Felidae, Mustelidae and carnivorous fish in the context of the renewal of the authorisation. The Panel concludes that taurine cannot be considered a nutritional additive for all poultry and porcine species.</p
Safety and efficacy of a feed additive consisting of Enterococcus lactis NCIMB 10415 for all animal species (Agri-King, Inc.)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on Enterococcus lactis NCIMB 10415 when used as a technological additive to improve ensiling of all types of fresh plant material for all animal species at a proposed minimum level of 1 × 108 colony forming units (CFU)/kg fresh plant material. The strain NCIMB 10415 was unambiguously identified as Enterococcus lactis, found not to belong to the hospital-associated clade of Enterococcus faecium and acquired antimicrobial resistance genes were not detected. Consequently, the FEEDAP Panel concluded that E. lactis NCIMB 10415 is safe for all animal species, for consumers of products from animals fed with the treated silage and for the environment. Regarding the safety for the user, the additive is considered irritant to eyes and a skin and respiratory sensitiser. Therefore, any exposure is considered a risk. The FEEDAP Panel concluded that the addition of E. lactis NCIMB 10415 at a minimum level of 1 × 108 CFU/kg to fresh plant material has the potential to improve the production and fermentation quality of silage made from all types of plant materials.</p
Efficacy of a feed additive consisting of ponceau 4R for its use in baits for freshwater fish (GIFAP)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the efficacy of ponceau 4R. Ponceau 4R is intended to be used as a sensory additive (functional group: (a) colourants: (i) substances that add or restore colour in feedingstuffs) in baits for freshwater fish up to a maximum content of 15 mg/kg in complementary feed. Ponceau 4R is intended to be incorporated in fishing baits in order to colour them and attract fish in freshwater (ponds, rivers), for both recreational and competitive fishing. The additive is not intended for use in aquaculture. The characterisation of the additive, its safety and its efficacy were evaluated in a previous opinion of the Panel. In that opinion, the Panel concluded that the use of ponceau 4R in the preparation of baits for freshwater fish under the proposed conditions of use is of no concern for the target animals, for the consumer and the environment. Regarding the user safety, the additive is not skin irritant but should be considered a skin and respiratory sensitiser. Inhalation and dermal exposure are considered a risk. The FEEDAP Panel could not conclude on the eye irritation potential of the additive. Finally, in the previous opinion, the Panel concluded that in absence of data no conclusion could be reached on the efficacy of ponceau 4R in freshwater fish baits. Based on the new data submitted by the applicant, the Panel concluded that ponceau 4R has the potential to be efficacious in colouring fishing baits under the proposed conditions of use.</p
Safety and efficacy of a feed additive consisting of l-cystine produced with Escherichia coli DSM 34232 for all animal species (Wacker Chemie AG)
No full textFollowing a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l-cystine produced with a genetically modified strain of Escherichia coli K-12 (DSM 34232) as a sensory feed additive (functional group: flavouring compounds) for all animal species. The l-cystine manufactured by fermentation with E. coli DSM 34232 did not give rise to any safety concern regarding the genetic modification of the production strain. No viable cells or DNA of the production strain were detected in the final product. The use of l-cystine produced by fermentation with E. coli DSM 34232 in feed was considered safe for the target species when supplemented at concentrations up to 25 mg/kg complete feed. The FEEDAP Panel considered that the use of l-cystine in animal nutrition is safe for the consumers of products from animals receiving the additive, and for the environment. Regarding user safety, the additive was not considered a skin and eye irritant, nor a skin sensitiser. As l-cystine is used in food as a flavouring compound, it is expected that it can provide a similar function in feed and no further demonstration of efficacy is necessary.</p