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The decline of breast feeding among immigrant mothers is of concern to transcultural nurses and other health care professionals. A descriptive survey of 30 Cuban and 30 Haitian immigrant mothers in South Florida explored their feeding and weaning beliefs and practices. Findings revealed that social, economic, and political factors in their country of origin and in South Florida affected their traditional health-culture beliefs and practices related to breast and bottle feeding and weaning, initial fluid intake, introduction of supplemental foods, and administration of vitamins, minerals, and medications. Implications for transcultural nursing care are presented. [ABSTRACT FROM AUTHOR]

Thirty immigrant Haitian mothers in Southeast Florida were interviewed regarding their beliefs and practices about preventive health care (illness prevention and health maintenance measures) for infants and preschool children (up to age 5). All mothers used preventive health care measures from both the Western biomedical and traditional Haitian ethnomedical (folk) systems. Ninety-seven percent used magico-religious measures; 47% administered home remedies; 47% gave children over-the-counter drugs; and 35% utilized a variety of measures to ensure cold air did not enter neonates and cause illness or pain. The Haitian mothers considered the preventive health care measures effective because the children remained healthy and will likely use them again. They sought consultation from a variety of individuals who formed their health management groups and child caretaker networks. Infants and toddlers were considered at higher risk than newborns for illness due to 'evil harm' inflicted by other people and/or voodoo spirits. Implications for transcultural nursing practice include developing community outreach programs, implementing nursing interventions that combine biomedical and ethnomedical preventive health care measures, and functioning as part of the health management group. The authors wish to thank Maude Vincent, R.N., for her assistance in data gathering and analysis. [ABSTRACT FROM AUTHOR]

Gesture-based screen readers like VoiceOver or TalkBack provide visually impaired users with a means to interact with digital content. However, there is a significant lack of both strategies and resources for teaching the use of these screen readers, and standardized teaching guidelines are notably absent. Furthermore, there is no free, universally designed, and accessible app for practicing gestures in mobile screen readers. This study aims to identify best practice strategies for teaching and practicing the use of gesture-based screen readers among visually impaired users, based on observations from an IT course directed at visually impaired individuals. Moreover, we present common challenges related to usability, attitudes, emotions, technical aspects, and user guidance and education, as well as key traits and facilitators for learning gesture-based screen readers. Lastly, we assess the feasibility of an app to practice gestures and propose a framework for a gesture practice app to enhance user accuracy and patience.

In this work, we propose a novel maturity model that suits the peculiarities of universal design of IT and ICT. The model is simply abbreviated as UDMM. It is domain-agnostic, targets intra-organizational application, and is free to use. Its design is influenced by maturity models in the related areas digital accessibility, usability, user experience, user-centered design, co-design and participatory design, as well as design-thinking. Besides a literature review, also interviews with stakeholders have been employed to gather insight for the model synthesis, and to ensure the model's proper theoretical foundation. The UDMM is currently undergoing further improvement iterations and will be tested and validated in practice in the future.

Mobile ICT, such as smartphones and tablets, has become integral for everyday tasks like finance, communication, and entertainment. While these technologies offer significant opportunities for integration and combating loneliness, visually impaired individuals still face challenges. These include practical barriers due to poor universal design, motivational hurdles, and inadequate lifelong education. In this paper, we aim to identify both the motivational and educational facilitators, as well as the technical and societal inhibitors, to digital skill development in mobile ICT among visually impaired individuals. Our approach involved participating as silent observers in an IT course for visually impaired users. Our study underscores that visually impaired individuals value mobile ICT for enhancing their daily lives. We identify opportunities, including key motivations to learn about ICT, and compile a list of useful apps and devices for visually impaired people. Simultaneously, we identify challenges related to technical and universal design, competence and societal issues, motivation, and attitudes, as well as security, privacy, and fraud concerns.

Bio-based fertilizers (BBFs) produced from organic waste contribute to closed-loop nutrient cycles and circular agriculture. However, persistent organic contaminants, such as per- and poly-fluoroalkyl substances (PFAS), polychlorobiphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), as well as polyaromatic hydrocarbons (PAHs) can be present in organic waste or be formed during valorization processes. Consequently, these hazardous substances may be introduced into agricultural soils and the food chain via BBFs. This study assessed the exposure of 84 target substances and extractable organic fluorine (EOF) in 19 BBFs produced from different types of waste, including agricultural and food industrial waste, sewage sludge, and biowaste, and through various types of valorization methods, including hygienization at low temperatures (<150 °C) as well as pyrolysis and incineration at elevated temperatures (150-900 °C). The concentrations in BBFs (ΣPFOS & PFOA: <30 μg kg -1 , Σ6PCBs: <15 μg kg -1 , Σ11PAHs: <3 mg kg -1 , Σ17PCDD/Fs: <4 ng TEQ kg -1 ) were found to be below the strictest thresholds used in individual EU countries, with only one exception (pyrolyzed sewage sludge, Σ11PAHs: 5.9 mg kg -1 ). Five BBFs produced from sewage sludge or chicken manure contained high concentrations of EOF (>140 μg kg -1 ), so monitoring of more PFAS is recommended. The calculated expected concentrations in soils after one BBF application (e.g. PFOS: <0.05 μg kg -1 ) fell below background contamination levels (PFOS: 2.7 μg kg -1 ) elsewhere in the literature. This was confirmed by the analysis of BBF-amended soils from field experiments (Finland and Austria). Studies on target legacy contaminants in sewage sludge were reviewed, indicating a general decreasing trend in concentration with an apparent half-life ranging from 4 (PFOS) to 9 (PCDD/Fs) years. Modelled cumulative concentrations of the target contaminants in agricultural soils indicated low long-term risks. Concentrations estimated and analyzed in cereal grains were low, indicating that exposure by cereal consumption is well below tolerable daily intakes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicolas Estoppey reports financial support was provided by EU Horizon 2020 research and innovation program under grant agreement 818,309 (LEX4BIO). Emma R. Knight reports financial support was provided by EU Horizon 2020 research and innovation program, through the project ZeroPM (101036756). Ian Allan reports financial support was provided by EU Horizon 2020 research and innovation program, through the project ZeroPM (101036756). Goril Aasen Slinde reports financial support was provided by EU Horizon 2020 research and innovation program under grant agreement 818,309 (LEX4BIO). Kari Ylivainio reports financial support was provided by EU Horizon 2020 research and innovation program under grant agreement 818,309 (LEX4BIO). Alicia Hernandez-Mora reports financial support was provided by EU Horizon 2020 research and innovation program under grant agreement 818,309 (LEX4BIO). Hans Peter H. Arp reports financial support was provided by EU Horizon 2020 research and innovation program, through the project ZeroPM (101036756). Hans Peter H. Arp reports financial support was provided by Research Council of Norway, through the Miljøforsk project SLUDGEFFECT (NFR 302371). Gerard Cornelissen reports financial support was provided by EU Horizon 2020 research and innovation program under grant agreement 818,309 (LEX4BIO). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The COVID-19 pandemic overwhelmed health systems, resulting in a surge in excess deaths. This study clustered countries based on excess mortality to understand their response to the pandemic and the influence of various factors on excess mortality within each cluster., Materials and Methods: This ecological study is part of the COVID-19 MORtality (C-MOR) Consortium. Mortality data were gathered from 21 countries and were previously used to calculate weekly all-cause excess mortality. Thirty exposure variables were considered in five categories as factors potentially associated with excess mortality: population factors, health care resources, socioeconomic factors, air pollution, and COVID-19 policy. Estimation of Latent Class Linear Mixed Model (LCMM) was used to cluster countries based on response trajectory and Generalized Linear Mixture Model (GLMM) for each cluster was run separately., Results: Using LCMM, two clusters were reached. Among 21 countries, Brazil, the USA, Georgia, and Poland were assigned to a separate cluster, with the mean of excess mortality z-score in 2020 and 2021 around 4.4, compared to 1.5 for all other countries assigned to the second cluster. In both clusters the population incidence of COVID-19 had the greatest positive relationship with excess mortality while interactions between the incidence of COVID-19, fully vaccinated people, and stringency index were negatively associated with excess mortality. Moreover, governmental variables (government revenue and government effectiveness) were the most protective against excess mortality., Conclusion: This study highlighted that clustering countries based on excess mortality can provide insights to gain a broader understanding of countries' responses to the pandemic and their effectiveness., Competing Interests: Declarations Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s).)

Background: Evolving imaging modalities, increased awareness, and prostate-specific antigen testing in men with synchronous metastatic prostate cancer (mHSPC) are expected to have prolonged survival. Here we analyze trends in survival among men diagnosed with synchronous metastatic prostate cancer in Denmark., Methods: Here, we included all men diagnosed with mHSPC (N = 12,017) in Denmark between January 1st, 1995, and December 31st, 2021. Men were followed until December 31st, 2022. Median time to death was calculated by the Kaplan Meier method and the 3-year risk of prostate cancer death per calendar year was estimated by the Aalen-Johansen estimator from time of diagnosis., Findings: Median follow-up was 9 years (IQR: 4-15), from 2015 59 % of the men with mHSPC had treatment beyond androgen depletion therapy. Median survival increased from 1.7 years (IQR: 1·3-2·0) to 3.8 years (IQR: 3·3-4·2) in men diagnosed in 1995 and 2018, respectively (p < 0·001), after which median survival was not reached. The prostate cancer-specific mortality three years after diagnosis decreased from 66 % (95 %CI: 60-72) in 1995 to 28 % (95 %CI: 25-32) in 2019 (p < 0·001). From the period 1995-1999 to 2015-2021 median overall survival increased from 1·7 years (IQR: 0·8-3·7) to 4·5 years (IQR: 2·4-not reached; p < 0·001) in men age < 65 years and from 1·5 years (IQR: 0·7-2·9) to 3·1 years (IQR: 1·6-5·7; p < 0.001) in men older than 74 years at diagnosis., Interpretation: The improved survival suggests that, among other contributing factors, implementing novel therapies has likely been efficacious outside the clinical trial setting. Still, most men diagnosed with synchronous metastatic prostate cancer will die of prostate cancer. As such the need for life-prolonging and age-tailored treatment trials remains evident., Competing Interests: Declaration of Competing Interest Hein V. Stroomberg has received travel expenses, and speaking and lecture fees from MSD Denmark, and project support from Pfizer Denmark outside of the scope of this manuscript. J. Thomas Helgstrand has received prior speaker fee from Astellas Nordic, and advisory and consultancy for Janssen, Recordati, Astellas, and Bayer outside the scope of this manuscript. Klaus Brasso has received speaker fees from Bayer Denmark outside the scope of this manuscript. Signe Benzon Larsen reports no conflicts of interest. Andreas Røder has received project support from Bayer Denmark and Pfizer Denmark, prior speaker fees from Astellas Nordic, and advisory and consultancy for Pfizer, Amgen, MSD, Sanofi, Janssen, Astra-Zeneca, Recordati, Astellas, Bayer, Orion, Ferrin, Medtronic, and Intuitive outside of the scope of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The PufX protein is found in the photosynthetic membranes of several purple bacteria and is involved in ubiquinol-ubiquinone exchange at the Q B site of the reaction center. We have studied quinone pool reduction in chromatophores from PufX + and PufX - strains of Rhodobacter capsulatus by time-resolved FTIR difference spectroscopy under and after continuous illumination. To our knowledge, it is the first time that quinone pool reduction has been directly followed in real time in Rba. capsulatus membranes. Thanks to the availability in the literature of IR marker bands for protein conformational changes, ubiquinone consumption, ubiquinol production, Q---QH 2 quinhydrone complex formation, as well as for RC-bound Q A - and Q B - semiquinone species, it is possible to follow all the molecular events associated with light-induced quinone pool reduction. In Rba. capsulatus PufX  +  chromatophores, these events resemble the ones found in Rba. sphaeroides wild-type membranes. In PufX - chromatophores the situation is different. Spectra recorded during 22.7 s of illumination showed a much smaller amount of photoreduced quinol, consistent with previous observations that PufX is required for efficient QH 2 / Q exchange at the Q B site of the RC. Q consumption and QH 2 formation are rapidly associated with Q A - formation, showing that the structure of the RC-LH1 complex in PufX - membranes does not provide efficient access to the Q B site of the RC to a large fraction of the quinone pool, evidently because the LH1 ring increases in size to impair access to the RC. The presence of a positive band at 1560 cm -1 suggests also the transient formation, in a fraction of chromatophores or of RC-LH1 complexes, of a Q---QH 2 quinhydrone complex. Experiments carried out after 2-flash and 10-flash sequences make it possible to estimate that the size of the quinone pool with access to the Q B site in PufX - membranes is ≥ 5 ubiquinone molecules per RC. The results are discussed in the framework of the current knowledge of protein organization and quinone pool reduction in bacterial photosynthetic membranes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN. Analysis of SNP rs924607 (TT, CC or CT) was performed in all enrolled patients with available blood samples with a TaqMan genotyping assay. Rates and grades of VIPN were assessed prospectively as part of the RICOVER-60 trial. CEP72 genotype could be assessed in 519 patients. VIPN data was available for 499/519 patients who were included in the final analysis. 286 (57%) patients developed VIPN of any grade during treatment. Grade 2-4 VIPN occurred in 33% (166/499) of patients. The high-risk CEP72 TT genotype at rs924607 was identified in 97/499 (19%) patients. The TT genotype was not correlated with VIPN in the overall study population compared to patients with either CC or CT genotypes (p = 0.748). However, in the subgroup of female patients, the TT genotype was associated with increased occurrence of any-grade VIPN as well as grade 2-4 VIPN as compared to patients with either CC or CT genotypes (p = 0.016 and p = 0.020, respectively). Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36., (© 2024. The Author(s).)

Angiotensin II (ANG II) has been shown to have central nervous system effects. Although tissue renin-angiotensin systems (RAS) have been demonstrated in multiple tissues, the existence of a brain RAS is still a matter of debate. These studies test for angiotensin release from brain slices prepared from adult male Sprague-Dawley rats and male and female renin knock-out rats using Chinese hamster ovary cells modified to express both the angiotensin II type 1 receptor and a fluorescent calcium indicator. Sniffer cells were placed on the slices and calcium transients were measured from those located on or adjacent to the median preoptic nucleus with and without stimulation of the subfornical organ. Bath application of tetrodotoxin (1 µM) significantly attenuated spontaneous events while abolishing evoked sniffer cell activity. Bath application of dl-AP4 (10 µM, glutamatergic antagonist) did not affect either spontaneous or evoked release. Incubating the slices with fluorocitrate to inactive astrocytes did not influence sniffer cell activity in the MnPO. Pharmacological experiments indicate that ANG II release is largely both renin (aliskiren 10 µM) and ACE-1 (captopril 100 µM) dependent. However, experiments with brain slices prepared from male and female Renin knock-out rats suggest that alternative synthetic pathways may exist. Finally, these studies demonstrate that increases in ANG II release are observed following 7 days of chronic intermittent hypoxia. These studies suggest the existence of a tissue-specific RAS in the brain that involves canonical and alternative ANG II synthetic pathways and is upregulated in an animal model of sleep apnea. NEW & NOTEWORTHY These studies used Chinese hamster ovary cells that were cloned to express an angiotensin receptor ( At1ra ) and a calcium indicator (R-GECO) to detect the release of angiotensin from brain slices containing the lamina terminalis of rats. Some of the experiments use tissue from renin knockout rats. The results support the existence of an angiotensin system in the brain that may involve alternative synthetic pathways and is upregulated by intermittent hypoxia.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80-91). Despite higher CR rates with R-CHOP-14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R-CHOP-14 and R-miniCHOP regarding overall survival (OS) (p = .88, HR 0.94, 95% CI = 0.47-1.90) and progression-free survival (PFS) (p = .26, HR 0.66, 95% CI = 0.32-1.36). At a median follow-up of 40 months, the 2-year OS rates were 56% with R-CHOP-14 and 53% with R-miniCHOP. Two-year PFS rates were 46% for R-CHOP-14 and 50% for R-mini-CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p = .72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R-miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Fructose metabolism by ketohexokinase (KHK) is implicated in a variety of metabolic disorders. KHK inhibition is a potential therapeutic strategy for the treatment of diseases including diabetes, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis. The first small-molecule KHK-inhibitors have entered clinical trials, but it remains unclear if systemic inhibition of KHK by small-molecules will eventually benefit patients. Here we report the discovery of BI-9787, a potent, zwitterionic KHK inhibitor characterized by high permeability and favorable oral rat pharmacokinetics. BI-9787 was identified by optimizing chemical starting points generated via a ligand-based virtual screening of Boehringer's virtual library of synthetically accessible compounds (BICLAIM). It serves as a high-quality in vitro and in vivo tool compound for investigating the role of fructose metabolism in disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bernd Nosse is an employee of Boehringer Ingelheim International. All other authors are employees of Boehringer Ingelheim Pharma GmbH & Co KG, which funded the research., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The GeneXpert® MRSA/SA SSTI test allows early detection of methicillin-resistant staphylococci in intraoperative samples of prosthetic joint infections (PJI) in order to stop early broad-spectrum antibiotics., Questions/purpose: (1) What is the rate of false-negative GeneXpert® MRSA/SA SSTI test results? (2) Does a false-negative GeneXpert® MRSA/SA SSTI test result increase the risk of treatment failure for the patient with a PJI? (3) What are the risk factors of a false-negative result?, Method: A retrospective study was carried out to compare all GeneXpert® assays to conventional cultures in prosthetic joint infections from April 1 st , 2012 to October 1 st , 2016. False-negative (FN) results (absence of methicillin-resistant staphylococci (MRS) with GeneXpert® test, but presence in the culture) were identified. We compared the rate of treatment failure between FN results and other test results and we established the risk factors of having a FN result., Results: Among the 612 GeneXpert® results, the rate of FN results was 3.6 % (22/612). We found a significant increase in treatment failures for prosthetic joint infection with a FN result with 14 treatment failures (14/22) compared to 198 treatment failures (198/590) in the other test results (OR, 2.1; 95 % CI, 1.3-3.4, p = 0.0019). Not considering suppressive antibiotics as a treatment failure, we found no significant difference in the rate of treatment failures between the false-negative tests and the other tests (OR, 1.36; 95 % CI, 0.66-2.81, p = 0.41). Tobacco use (OR, 3.8; 95 % CI, 1.4-10.3, p = 0.004), ASA classification (OR, 2,4; 95 % CI, 0.9-6.9, p = 0.064), history of infection in the joint (OR, 3.2; 95 % CI, 1.2-9.6, p = 0.007), chronic infections (OR, 3.2; 95 % CI, 0.8-17.5, p = 0.01) and polymicrobial infections (OR, 3.2; 95 % CI, 1.1-9.2, p < 0.0001) were risk factors for a FN result., Conclusion: GeneXpert® tests in prosthetic joint infections showed a low rate of FN results. An increased risk of treatment failures was observed in FN results only when long-term use of suppressive antibiotics was considered as treatment failure., Level of Evidence: III; Diagnostic retrospective case control study., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: The majority of metastatic renal cell carcinoma (mRCC) patients receive one or more VEGFR TKI agents, alone or in combination with an immune-oncology (IO) agent or an mTOR inhibitor. To date, the cost of adverse events (AEs) common to VEGFR TKIs has not been quantified. This study estimated the potential impact of differences in VEGFR TKI AE profiles on treatment cost efficiency in the relapsed/refractory (R/R) setting., Methods: Patients with documented mRCC who were treated with VEGFR TKI therapies between Jan 2015 and Mar 2021 were identified using EMR. ICD-10 diagnosis codes were used to identify the first occurrence of each class effect AE. Patients were matched to 3rd party insurance claims, and costs associated to TKI AEs within 90 days of index event were captured. Average per patient AE cost data was calculated and applied to published incidence data to estimate regimen-specific AE total cost burden within a hypothetical commercial plan for mRCC patients undergoing treatment in the R/R setting., Results: The highest total cost for AE management was attributed to lenvatinib and everolimus use at $13,303, followed closely by sunitinib at $13,092. Tivozanib treatment was associated with the lowest total cost of AE management at $7,523, driven by the relatively lower incidence of certain high-cost AEs., Conclusions: The estimated costs of managing VEGFR TKI class-effect AEs were lowest with tivozanib, and highest with lenvatinib and everolimus, indicating potentially differential healthcare resource burden by TKI regimen. The use of tivozanib in the 3 L + mRCC setting suggests potential costs offsets when compared to other TKI regimens., (© 2024. The Author(s).)

Quality assessment, including inspecting the images for artifacts, is a critical step during magnetic resonance imaging (MRI) data acquisition to ensure data quality and downstream analysis or interpretation success. This study demonstrates a deep learning (DL) model to detect rigid motion in T 1 -weighted brain images. We leveraged a 2D convolutional neural network (CNN) trained on motion-synthesized data for three-class classification and tested it on publicly available retrospective and prospective datasets. Grad-CAM heatmaps enabled the identification of failure modes and provided an interpretation of the model's results. The model achieved average precision and recall metrics of 85% and 80% on six motion-simulated retrospective datasets. Additionally, the model's classifications on the prospective dataset showed 93% agreement with the labeling of a radiologist a strong inverse correlation (-0.84) compared to average edge strength, an image quality metric indicative of motion. This model is aimed at inline automatic detection of motion artifacts, accelerating part of the time-consuming quality assessment (QA) process and augmenting expertise on-site, particularly relevant in low-resource settings where local MR knowledge is scarce., (© 2024 John Wiley & Sons Ltd.)

Previous epidemiological studies on the associations between polyunsaturated fatty acids (PUFAs) and cancer incidence have been inconsistent. We investigated the associations of plasma omega-3 and omega-6 PUFAs with the incidence of overall and 19 site-specific cancers in a large prospective cohort. 253,138 eligible UK Biobank participants were included in our study. With a mean follow-up of 12.9 years, 29,838 participants were diagnosed with cancer. The plasma levels of omega-3 and omega-6 PUFAs were expressed as percentages of total fatty acids (omega-3% and omega-6%). In our main models, both omega-6% and omega-3% were inversely associated with overall cancer incidence (HR per SD = 0.98, 95% CI = 0.96-0.99; HR per SD = 0.99, 95% CI = 0.97-1.00; respectively). Of the 19 site-specific cancers available, 14 were associated with omega-6% and five with omega-3%, all indicating inverse associations, with the exception that prostate cancer was positively associated with omega-3% (HR per SD = 1.03, 95% CI = 1.01-1.05). Our population-based cohort study in UK Biobank indicates small inverse associations of plasma omega-6 and omega-3 PUFAs with the incidence of overall and most site-specific cancers, although there are notable exceptions, such as prostate cancer., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Cardiovascular disease remains the leading cause of death worldwide, with mortality rates increasing annually. This underscores the urgent need for accurate diagnostic and monitoring tools. Electrochemical detection has emerged as a promising method for swiftly and precisely measuring specific biomarkers in bodily fluids. This approach is not only cost-effective and efficient compared to traditional clinical methods, but it can also be tailored to detect individual biomarkers, which makes it particularly well-suited for point-of-care (POC) applications. The ability to conduct testing at the point of care is crucial for timely interventions and personalized disease management, empowering healthcare providers to tailor treatment plans based on real-time biomarker data. Thanks to recent advancements in nanomaterials, we've seen significant progress in electrochemical detection, leading to the development of specialized rapid immunoassay systems. These systems utilize specific antibodies to target molecules, expanding the range of detectable biomarkers. This innovation has the potential to revolutionize the diagnosis and treatment of cardiovascular diseases by enhancing detection sensitivity and specificity. Ultimately, these advancements aim to improve patient outcomes by enabling earlier diagnosis, more precise monitoring, and personalized therapeutic interventions, which will contribute to more effective management of cardiovascular health globally.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world and anti-vascular endothelial growth factor (VEGF) injections have been the standard of care for the wet/neovascular variant since 2004. Currently, there are conflicting reports regarding its effect on the choroid, which supplies outer retina with oxygen and other nutrients. We synthesize available information of anti-VEGF on choroidal thickness (CT) in treatment-naïve typical neovascular AMD patients during the initial 12-week loading phase. We found 43 studies involving 1901 eyes from 1878 patients were included. Meta-analysis of 35 studies reporting CT at baseline and after 12 weeks suggested a significant decrease in CT with anti-VEGF treatment. A greater mean change with aflibercept compared to ranibizumab was found in subgroup analyses of sub-foveal CT in types 1 and 2 macular neovascularization. The long-term consequences of reduced CT in neovascular AMD remain unclear and require further targeted studies., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Early identification and fluid resuscitation are recognized performance measures within sepsis care. Despite fluid resuscitation, fluid goals are often not achieved in the prehospital environment. Furthermore, description of implementation process and evaluation of implementation success are historically underreported in prehospital research. The objective of this study was to contextualize and evaluate the system-wide implementation of a novel fluid resuscitation device, the LifeFlow PLUS ® , in the treatment of prehospital sepsis patients., Methods: A single urban emergency medical services (EMS) system internally decided to adopt a novel fluid resuscitation device. This EMS system added the device to the clinical care guidelines of suspected sepsis patients. Prior to and during implementation of the new guidelines, several strategies were undertaken to promote consistent, appropriate system-wide use of the device. A mixed methods study design was deployed. Surveys of EMS clinicians and leaders assessed perceptions of the device and sepsis education prior to field implementation of the device. Clinician and leader semi-structured interviews assessed implementation experience and device adoption. Document analysis evaluated deployment of implementation strategies. Data were triangulated to contextualize implementation and evaluate success., Results: Clinician (88%) and leader (91%) confidence in appropriate clinician device use and device superiority for sepsis care (73 and 100%, respectively) were high. Clinicians (58%) were less likely to view the device as easy to implement compared to leaders (73%). Three themes were developed from semi-structured interviews, including "exposure" to the device, "reinforcing factors" to prompt device use, and "clinician buy-in." Twenty unique implementation strategies (e.g., dynamic trainings , mandating change ) were used to promote successful system-wide device adoption., Conclusions: The overall implementation success of this novel fluid resuscitation device was moderate. Barriers to adoption included complexity of clinical decision-making and ease of device use. Facilitators to adoption included the use of multiple modes of education, clinical reminders, presenting evidence of device benefit, and prehospital culture. Prior to future prehospital implementation programs, EMS systems should focus on identifying and addressing key barriers and facilitators to improve adoption.

Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their DNA products remain largely unknown. We show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis through rolling circle reverse transcription of a noncoding RNA (ncRNA). Programmed template jumping on the ncRNA generates a concatemeric cDNA, which becomes double-stranded upon viral infection. This DNA product constitutes a protein-coding, nearly endless open reading frame ( neo ) gene whose expression leads to potent cell growth arrest, restricting the viral infection. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.

Background: Cancer survivors experience a high prevalence of functional impairments. Rehabilitation interventions include an expansive array of services that can help optimize function, address pain, decrease symptom burden, and improve quality of life. Nonetheless, rehabilitation services remain underutilized. Thus, it is important to enhance the understanding of and establish guidelines for specific rehabilitation disciplines and interventions., Methods: This is a gap analysis of rehabilitation recommendations in published oncology guidelines from selected nationally recognized organizations. Symptom-specific guidelines and cancer type-specific guidelines were analyzed for inclusion of common functional impairments (fatigue, pain, peripheral neuropathy, cognitive dysfunction, and lymphedema) and the rehabilitation discipline recommendations., Results: The prevalence of recommendations for rehabilitation in cancer type-specific guidelines was 29%, and was higher in symptom-specific guidelines at 60%. However, the frequency of specific rehabilitation disciplines (physiatry, physical therapy, occupational therapy, speech-language pathology, and rehabilitation psychology/neuropsychology) was notably lower. Overall rehabilitation was mentioned in 33% and physiatry in 18%. Nonrehabilitation specialties were recommended in 18% of the guidelines. No specialty referral was endorsed in 53% of guidelines in which 1 of 5 symptoms were discussed. This highlights the relative paucity of recommendations for specific rehabilitation disciplines in oncology guidelines. The more general term "rehabilitation" was included more frequently but lacks critical guidance for oncology providers. Other crucial rehabilitation services may be underrecognized and underutilized. Rehabilitation specialists must work to improve patient access and the presence of indicated specific rehabilitation disciplines and goals within guidelines., Conclusions: Most oncology guidelines do not include specific recommendations for rehabilitation disciplines. However, including specific rehabilitation disciplines is more common in symptom-specific guidelines. With a stronger evidence base and increased involvement of rehabilitation specialists in guideline development, rehabilitation recommendations in oncologic guidelines may be more precise, leading to improved utilization of rehabilitation services to optimize function and quality of life.

Light intensity is a critical environmental factor influencing plant growth and development. To survive high light conditions, plants have evolved various protective mechanisms, including non-photochemical quenching (NPQ). However, NPQ can limit effective photosynthetic yield when transitioning to low light conditions. This phenomenon is underexplored in cassava (Manihot esculenta ), a starchy storage root crop known for its high biological efficiency and climate resilience. To address this knowledge gap, we assessed the photoprotective abilities and growth responses of six cassava varieties under natural environmental light conditions (control) and intermittent high light (IHL) conditions by adding 900μmolm-2 s-1 using full-spectrum LED lights, on top of the natural ambient daylight. Our results demonstrated a significant impact of light treatment on aboveground biomass, total crop biomass, chlorophyll a and b content, photosynthetic rate, and NPQ values during transitions from low to high light and vice versa. Notably, cassava variety 'Sree Suvarna' exhibited the highest yield under both control and IHL conditions. These findings suggest that screening cassava varieties for their ability to postpone photoinhibition and recover quickly from photoinhibition may enhance photosynthetic performance. Such strategies have important implications for improving the efficiency and resilience of cassava crops, ultimately contributing to sustainable agricultural productivity.

Background: Postoperative periprosthetic femoral fracture (POPFF) after total hip replacement (THR) requires complex surgery and is associated with a high morbidity, mortality, and cost. Although the United Kingdom based National Joint Registry (NJR) captures over 95% of THRs treated with revision, before June 2023 it did not capture POPFF treated with fixation. We aimed to estimate the incidence and epidemiology of POPFF treated with either surgery in England., Methods and Findings: We performed a retrospective analysis of a mandatory, prospective database (NJR) linked to Hospital Episode Statistics (HES). All linkable primary THRs between 01/01/2004 and 31/12/2020 were included. Revision or fixation of POPFF were identified using a combination of procedural and diagnosis codes. We identified 809,832 THRs representing 5,542,332 prosthesis years at risk. A total of 5,100 POPFF were identified that had been surgically treated by revision, fixation, or both, and 2,831 of these fractures were treated with fixation alone, meaning 56% were not represented with revision data alone. The incidence of POPFF needing surgery was 0.92 (95% CI 0.90, 0.95) per 1,000 prostheses years. This incidence was higher in patients over the age of 70 at the time of primary THR (1.31 [95% CI 1.26, 1.35] per 1,000 prostheses years) and for patients who underwent THR for hip fracture (2.19 [95% CI 1.97, 2.42] per 1,000 prostheses years). This incidence appears to be increasing year on year. The cumulative probability of sustaining a POPFF within 10 years of THR was 1% and over 15% of patients died within 1 year of surgery for a POPFF., Conclusions: To date, the incidence of POPFF may have been underestimated with over 50% of cases missed if the case identification in this study is correct. After including these cases, we observed that POPFF is the largest reason for major reoperation following THR and patients sustaining these injuries have a high risk of death. The prevention and treatment of POPFF and requires further resource allocation and research., Competing Interests: HP is a NIHR senior investigator and MHRA advisor. In the latter role, he advised MHRA regarding the incidence and risk factors associated with the post-operative peri-prosthetic femoral fractures. In particular, this was to identify the risks associated with one of the commonly used stems (CPT manufactured by Zimmer Biomet). This was a voluntary role and no funding from MHRA was/is associated with it. HP (as a Chief Investigator) receives institutional funding from Zimmer Biomet, Depuy Synthes, Allay Therapeutics, Paradigm Pharma and Invibio. In particular, Zimmer Biomet has funded University of Leeds in relation to the on-going and previous research in the field of peri-prosthetic fractures. HP is a paid consultant to Zimmer Biomet for the work in the field of peri-prosthetic fractures and arthroplasty related teaching / training. HP has also received personal funding from the following industry organisations (unrelated to the topic of this work): Invibio, Medacta International, Smith and Nephew, MATOrtho, Microport, Teleflex, Allay Therapeutics and Paradigm Pharmaceuticals. HP has a stock option with Allay Therapeutics. HP holds two patents (through University of Leeds - in the field of implantable sensors and recharging apparatus). None of these roles / funding from any of the industry organisations (either to HP or to his institution) influenced the design; collection, analysis, and interpretation of data presented in this manuscript), (Copyright: © 2024 Lamb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pseudomyogenic hemangioendothelioma (PMHE), a rare soft tissue tumor predominantly affecting young adults, often presents as multiple nodules in various tissue planes of a limb. Malignant transformation and metastatic disease are unusual and pose diagnostic and therapeutic challenges. A 17-year-old patient from Western India, with a history of recurrent excisions for a toe swelling presented to our center for evaluation and management. A below-knee amputation was performed, and histopathology revealed PMHE. Adjuvant therapy was deemed unnecessary given the borderline nature of the tumor. Shortly thereafter, he developed features of local recurrence and underwent above-knee amputation. An expert histopathological review confirmed the diagnosis and noted features of malignant transformation-progression to a higher grade with greater cytological atypia, confluent growth, and increased mitotic activity over time. Upon further distant progression in the lung, he was started on a palliative regimen of weekly paclitaxel, vinblastine, and propranolol but eventually succumbed to his illness. In contrast to conventional descriptions of low mitotic activity, minimal nuclear atypia, and absence of necrosis, our patient exhibited increased mitotic rates, nuclear atypia, and evolving necrosis in serial histopathological evaluations. The fulminant clinical progression within a short interval was also atypical. Our patient's clinical course underscores the need for meticulous histopathological and molecular characterization and vigilant clinical surveillance after resection in patients with PMHE. Providing the standard of care for malignant disease in the adjuvant setting is challenging owing to the rarity and the lack of treatment guidelines., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Very low-field MR has emerged as a promising complementary device to high-field MRI scanners, offering several advantages. One of the key benefits is that very low-field scanners are generally more portable and affordable to purchase and maintain, making them an attractive option for medical facilities looking to reduce costs. Very low-field MRI systems also have lower RF power deposition, making them safer and less likely to cause tissue heating or other safety concerns. They are also simpler to maintain, as they do not require cooling agents such as liquid helium. However, these portable MR scanners are impacted by temperature, lower magnetic field strength, and inhomogeneity, resulting in images with lower signal-to-noise ratio (SNR) and higher geometric distortions. It is essential to investigate and tabulate the variations in these parameters to establish bounds so that subsequent in vivo studies and deployment of these portable systems can be well informed., Purpose: The aim of this work is to investigate the repeatability of image quality metrics such as SNR and geometrical distortion at 0.05 T over 10 days and three sessions per day., Methods: We acquired repeatability data over 10 days with three sessions per day. The measurements included temperature, humidity, transmit frequency, off-resonance maps, and 3D turbo spin echo (TSE) images of an in vitro phantom. This resulted in a protocol with 11 sequences. We also acquired a 3 T data set for reference. The image quality metrics included computing SNR and eccentricity (to assess geometrical distortion) to investigate the repeatability of 0.05 T image quality. The image reconstruction included drift correction, k-space filtering, and off-resonance correction. We computed the experimental parameters' coefficient of variation (CV) and the resulting image quality metrics to assess repeatability. We have explored the impact of electromagnetic interference (EMI) on image quality in very low-field MRI. The investigation involved varying both the distance and amplitude of the EMI-producing coil from the signal generator to analyze their effects on image quality., Results: The range of temperature measured during the study was within 1.5 °C. The off-resonance maps acquired before and after the 3D TSE showed similar hotspots and were changed mainly by a global constant. The SNR measurements were highly repeatable across sessions and over the 10 days, quantified by a CV of 6.7%. The magnetic field inhomogeneity effects quantified by eccentricity showed a CV of 13.7%, but less than 5.1% in two of the three sessions over 10 days. The use of conjugate phase reconstruction mitigated geometrical distortion artifacts. Temperature and humidity did not significantly affect SNR or mean frequency drift within the ranges of these environmental factors investigated. The EMI experiment showed that as the amplitude increased the SNR decreased, and concurrently the root mean square of the background increased with a rise in EMI amplitude or a reduction in distance., Conclusions: We found that humidity and temperature in the range investigated did not impact SNR or frequency. Based on the CV values computed session-wise and for the overall study, our findings indicate high repeatability for SNR and magnetic field homogeneity., (© 2024 John Wiley & Sons Ltd.)

Background: Extracellular volume (ECV) correlates with the degree of liver fibrosis., Purpose: To analyze the performance of liver MRI-based ECV evaluations with different blood pool measurements at different time points., Study Type: Prospective., Sample: 73 consecutive patients (n = 31 females, mean age 56 years) with histopathology-proven liver fibrosis., Field Strength/sequence: 3T acquisition within 90 days of biopsy, including shortened modified look-locker inversion recovery T1 mapping., Assessment: Polygonal regions of interest were manually drawn in the liver, aorta, vena cava, and in the main, left and right portal vein on four slices before and after Gd-DOTA administration at 5/10/15 minutes. ECV was calculated 1) on one single slice on portal bifurcation level, and 2) averaged over all four slices., Statistical Tests: Parameters were compared between patients with fibrosis grades F0-2 and F3-F4 with the Mann-Whitney U and fishers exact test. ROC analysis was used to assess the performance of the parameters to predict F3-4 fibrosis. A P-value <0.05 was considered statistically significant., Results: ECV was significantly higher in F3-4 fibrosis (35.4% [33.1%-37.6%], 36.1% [34.2%-37.5%], and 37.0% [34.8%-39.2%] at 5/10/15 minutes) than in patients with F0-2 fibrosis (33.3% [30.8%-34.8%], 33.7% [31.6%-34.7%] and 34.9% [32.2%-36.0%]; AUC = 0.72-0.75). Blood pool T1 relaxation times in the aorta and vena cava were longer on the upper vs. lower slices at 5 minutes, but not at 10/15 minutes. AUC values were similar when measured on a single slice (AUC = 0.69-0.72) or based on blood pool measurements in the cava or portal vein (AUC = 0.63-0.67 and AUC = 0.65-0.70)., Data Conclusion: Liver ECV is significantly higher in F3-4 fibrosis compared to F0-2 fibrosis with blood pool measurements performed in the aorta, inferior vena cava, and portal vein at 5, 10, and 15 minutes. However, a smaller variability was observed for blood pool measurements between slices at 15 minutes., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 3., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers. We also aimed to identify population specific BRCA1/2 mutation hotspots, to enable the development of more affordable testing strategies. We identified 921 patients with breast and ovarian cancer who underwent mutation testing. The target enrichment was followed by targeted NGS in 772 patients and an allele-specific PCR (ASPCR) based genotyping for BRCA1:c.68&#95;69delAG (or 185delAG), was carried out in 149 patients. We identified 188 (20.4%) patients with BRCA1/2 variants: 118 (62.8%) with pathogenic/likely pathogenic and 70 (37.2%) with VUS. The 185delAG was identified as a recurrent mutation in the Southern Indian population, accounting for 24.6% of the pathogenic variants. In addition, a family history of breast, ovary, pancreas, or prostate (BOPP) cancer was found to be associated with an increased risk of identifying a deleterious BRCA1/2 variant [OR = 2.11 (95% CI 1.45-3.07) p ≤ 0.001]. These results suggest that Targeted NGS is a sensitive and specific strategy for BRCA testing. For Southern Indian patients, a two-tiered approach can be considered: Initial screening with ASPCR for BRCA1 185delAG followed by NGS for those testing negative. Expanding the gene panel and identifying other population-specific mutation hot spots is a promising area with potential for improvements in testing and treatment strategies., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Sex differences are recognized in pulmonary hypertension. However, the progression of disease with regard to vascular lesion formation and circulating cytokines/chemokines is unknown. To determine whether vascular lesion formation, changes in hemodynamics, and alterations in circulating chemokines/cytokines differ between males and females, we used a progressive model of pulmonary arterial hypertension (PAH), Sugen/hypoxia, and analyzed cohorts of male and female rats at time points suggested to indicate worsening disease. Our analysis included echocardiography for hemodynamics, morphometry, immunofluoresecence, and chemokine/cytokine analysis of plasma at each time point in both sexes. We found that male rats had significantly increased Fulton index, compared with those for females at each time point, as well as increased medial artery thickening at 8 weeks of PAH. Furthermore, females exhibited fewer obliterative vascular lesions than males at our latest time point. Our data also show increased IL-4, granulocyte-macrophage colony-stimulating factor, IL-10, and macrophage interacting protein-1α that were not observed in females, whereas females were observed to have increased RANTES (whose name derives from Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted) and CXCL-10 that were not found in males. Males also have increased infiltrating macrophages in vascular lesions, compared with females. We found that development of progressive PAH in hemodynamics, morphology, and chemokine/cytokine circulation differs significantly between males and females. These data suggest a macrophage-driven pathology in males, whereas there may be T cell protection from vascular damage in females with PAH.

Objective: To characterize transimpedance matrix (TIM) heatmap patterns in patients at risk of labyrinthine abnormality to better understand accuracy and possible TIM limitations., Study Design: Retrospective review of TIM patterns, preoperative, and postoperative imaging., Setting: Tertiary referral center., Patients: Patients undergoing cochlear implantation with risk of labyrinthine abnormality., Intervention: None., Results: Seventy-seven patients were evaluated. Twenty-five percent (n = 19) of patients had a TIM pattern variant identified. These variants were separated into 10 novel categories. Overall, 9% (n = 6) of electrodes were malpositioned on intraoperative x-ray, of which 50% (n = 3) were underinserted, 17% (n = 1) were overinserted, 17% (n = 1) had a tip foldover, and 17% (n = 1) had a coiled electrode. The number of patients with a variant TIM pattern and normal x-ray was 18% (n = 14), and the number of patients with normal TIM pattern and malposition noted on x-ray was 3% (n = 2; both were electrode underinsertions that were recognized due to open circuits and surgical visualization).A newly defined skip heat pattern was identified in patients with IP2/Mondini malformation and interscalar septum width <0.5 mm at the cochlear pars ascendens of the basal turn., Conclusions: This study defines novel patterns for TIM heatmap characterization to facilitate collaborative and comparative research moving forward. In doing so, it highlights a new pattern termed skip heat, which corresponds with a deficient interscalar septum of the cochlea pars ascendens of the basal turn in patients with IP2 malformation. Overall, the data assist the surgeon in better understanding the implications and limitations of TIM patterns within groups of patients with risk of labyrinthine abnormalities., Competing Interests: Conflicts of interest and source of funding: Dr. J Thomas Roland Jr. is a consultant for Cochlear Americas and received research funding for CI-related projects, which are not affiliated with this research., (Copyright © 2024, Otology & Neurotology, Inc.)

Introduction: The GeneXpert® MRSA/SA SSTI (Methicillin Resistant Staphylococcus aureus/S. aureus skin and soft tissue infection) PCR test allows early detection of methicillin resistance in staphylococci. This test was developed for skin infections and has been evaluated for prosthetic joint infections but, to our knowledge, has not been evaluated for hardware infections outside of arthroplasties. Furthermore, we conducted a retrospective study in patients with non-prosthetic osteosynthesis hardware aiming: (1) to identify the diagnostic values of the PCR test compared to conventional cultures and the resulting rate of appropriate antibiotic therapy; (2) to identify the rate of false negative (FN) results; (3) to identify and compare the rates of failure of infectious treatment (FN versus others); (4) to search for risk factors for FN of the PCR test., Hypothesis: The PCR test allowed early and appropriate targeting of antibiotic therapy., Material and Methods: The results of PCR tests and conventional cultures for osteoarticular infections of non-prosthetic hardware over four years (2012-2016) were compared to identify the diagnostic values of using the results of conventional culture as a reference and the rate of appropriate antibiotic therapies. Infectious management failures between the results of the FN group and the others were compared, and variables associated with a FN of the PCR test were identified., Results: The analysis of 419 PCR tests allowed us to establish a sensitivity of 42.86%, a specificity of 96.82%, a positive predictive value of 60% and a negative predictive value of 93.83%. Using the results of the PCR test for the targeting of postoperative antibiotic therapy, it was suitable for staphylococcal coverage in 90.94% (381/419). The rates of patients for whom infectious treatment failed were not significantly different between the FN group and the other patients (20.8% versus 17.7%, respectively; Hazard Ratio=1.12 (95%CI 0.47-2.69, p=0.79)). A skin opening during the initial trauma (p=0.005) and a polymicrobial infection were significantly associated with a risk of FN from the PCR test (p<0.001)., Conclusion: The PCR test makes it possible to reduce the duration of empirical broad-spectrum antibiotic therapy during the treatment of an infection of osteosynthesis hardware but causes a lack of antibiotic coverage in 9.06% of cases., Level of Evidence: III; diagnostic case control study., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies., Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose., Results: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors., Conclusions: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)