Citations

ABSTRACT Despite advances in therapy, extramedullary disease (EMD) remains an aggressive form of multiple myeloma associated with poor outcomes. Patients with true EMD, in which plasmacytomas have become completely independent of bone, have a particularly poor prognosis. The pathogenesis of EMD is driven by complex mechanisms involving loss of adhesion molecules, heterogeneous genetic and epigenetic changes, and a solid tumor‐like architecture within the microenvironment. Although the introduction of advanced imaging techniques and immunotherapy has led to improved detection and more promising outcomes and regimens, respectively, more prospective studies dedicated to true EMD are needed.

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well‐structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of the more detailed information and links available at the www.guidetopharmacology.org website, the printed guide serves as a permanent, citable, point‐in‐time record, that remains stable despite ongoing updates to the online database. The full contents of this publication can be found at https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70233 . The Concise Guides provide expert‐curated recommendations of ‘Gold Standard’ selective pharmacological tools, available either commercially or as donations, which enable the identification of individual drug targets or families of drug targets. While the Concise Guide offers a more streamlined overview, more comprehensive information, including detailed pharmacological profiles and links to multiple online databases, is available through the Guide to Pharmacology website. The 2025/26 edition of the Concise Guide is based on material current as of mid‐2025, and supersedes all previous editions, including the 2023/24 Guide, and earlier Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), and as such provides official IUPHAR classification and nomenclature for human drug targets, where applicable. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. Each section includes nomenclature guidance, concise summaries, information of the best available pharmacological tools, key references, and suggestions for further reading.

Purpose: These consensus guidelines by the American Clinical Neurophysiology Society (ACNS) describe best practices for performing intraoperative Electrocorticography (ioECoG) using subdural or depth electrodes for adult and pediatric population. Methods: A group of ACNS members was convened to develop technical standards for performing ioECoG. PubMed searches were performed to identify pertinent peer-reviewed literature. Sections were assigned to individual authors based on expertise. Consensus was achieved during subsequent group discussions to develop evidence-based recommendations to the extent possible. Recommendations: Communication between the neurosurgical and the neurophysiology teams is essential in verifying and documenting the location of the contacts. Most authors recommend ioECoG recordings of at least 5 and up to 30 minutes in duration to allow for sufficient observation of interictal activity. The anesthesia should be adjusted to allow continuous EEG activity and to minimize the effect on the ioECoG recording during general anesthesia or awake surgery. The surgical procedure and technical report should separate ioECoG recordings to define the irritative zone from ioECoG findings during functional mapping. The neurophysiology physician’s physical presence in the operating room is required in the definition of the services. Conclusion: These consensus guidelines by the ACNS describe best practices for performing intraoperative ECoG based on published literature and expert consensus.

Uncontrolled systemic inflammatory responses are a critical pathological feature of fatal Ebola virus (EBOV) infection. While some inflammatory responses may originate from mononuclear phagocytes (MNPs), nonimmune cells vastly outnumber MNPs and may be an important source of inflammation. Here, we demonstrated that highly virulent EBOV induced a high and sustained pro-inflammatory response compared to less virulent ebolaviruses in non-MNPs through TLR4-independent NF-κB activation. We identified the EBOV matrix protein VP40 as a potent activator of NF-κB in non-MNPs, whose intrinsic inflammatory activation ability is higher than VP40 proteins from less virulent ebolaviruses. This suggests that VP40 is a virulence determinant inducing distinct degrees of pro-inflammatory responses among ebolaviruses. Mechanistically, VP40 activated the NF-κB signaling pathway, primarily via TNFR1 using a ligand-independent mechanism. These findings reveal mechanisms that may drive systemic inflammation and promote EBOV pathogenesis, suggesting potential therapeutic strategies to mitigate immune dysregulation in severe EBOV infections.

OBJECTIVES: Current research does not address the existence and impact of structured tele-critical care (TCC) training on the delivery of care in the ICU. This pilot study aimed to evaluate the association between on boarding elements focused on training and clinicians perceptions of delivery of care. DESIGN: Cross-sectional survey study. SETTING AND PARTICIPANTS: Critical Care professionals at four U.S. hospitals, professional meetings and Society of Critical Care Medicine’s International Membership base. Participants were active clinicians who practice in the TCC setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 432 participants responded to the survey, 227 met the eligibility criteria (52.5%) and were included in the analysis. Respondents were a multi-professional group of TCC clinicians aged between 35–55 years of age (56.4%). Seventy-four percent of respondents reported having orientation before providing TCC, 46% reported having formal mentorship, and 66% reported formal training on their institutional platform. Provision of orientation before participating in a TCC program was associated with higher ratings of feeling prepared (odds ratio [OR], 3.52; p < 0.001) and feeling accepted as part of the ICU team (OR, 2.21; p = 0.008). Mentorship was associated with feeling more prepared (OR, 8.2; p < 0.001) and higher comfort in delivering care (OR, 2.78; p = 0.016). Platform training was associated with feeling more prepared (OR, 4.66; p < 0.001), comfortable in delivering care (OR, 3.6; p = 0.002), feeling accepted as part of the team (OR, 3.18; p < 0.001), and more likely to participate in quality improvement (OR, 2.51; p = 0.001). A site visit also made a positive impact in feeling prepared (OR, 2.86; p < 0.001), comfortable (OR, 4.95; p = 0.002), feeling like recommendations were accepted (OR, 3.73; p < 0.001), more likely to recommend TCC (OR, 3.18; p = 0.001), and participating in quality improvement (OR, 3.24; p < 0.001). CONCLUSIONS: In this pilot study, structured training utilizing orientation, mentorship, and platform training as surrogates, along with a site visit before beginning delivery of care in a TCC setting, were associated with more positive perceptions in the delivery of care domains assessed. We highlight potentially important factors that warrant further evaluation and assessment of the need for standardization across TCC programs.

Importance Emergency department (ED) visits for people with dementia often involve care (including the admission or discharge decision) with lasting effects on quality of life. Home time—a claims-based measure of days alive and outside of institutional care—provides a patient-centered way to assess downstream outcomes of ED care in this population. Objective To examine variations in home time following an ED visit by patient, facility, and visit characteristics among veterans with dementia. Design, Setting, and Participants This national retrospective cohort study used US Department of Veterans Affairs (VA) health care system data sources. Participants were veterans aged 65 to 110 years with dementia with an eligible Veterans Health Administration ED visit in fiscal years 2017 (October 1, 2016, through September 30, 2017) and/or 2018 (October 1, 2017, through September 30, 2018). Data were analyzed from May 1, 2024, to May 15, 2025. Exposures Patient, ED facility, and ED visit factors. Main Outcomes and Measures Home time, operationalized for modeling as days not at home in the 180 days after the index ED visit. Associations between patient, ED facility, and ED visit characteristics and home time were assessed using a negative binomial model. Results The study included 51 707 veterans with dementia (mean [SD] age, 79.9 [8.59] years; 97.6% male; 52.2% married). The mean (SD) number of days not at home within 180 days was 21.7 (34.5). Of the total cohort, 4.5% never returned home in the 180 days after their ED visit, while 18.2% had all subsequent days at home. ED admission (vs discharge) disposition was the factor associated with the largest increase in days not at home (rate ratio [RR], 3.18; 95% CI, 3.08-3.29). Patient factors associated with more days not at home included very high frailty (RR, 1.27; 95% CI, 1.21-1.33), unhoused status (RR, 1.50; 95% CI, 1.39-1.63), unmarried status (never married: RR, 1.24 [95% CI, 1.16-1.32]; divorced, separated, or widowed: RR, 1.24 [95% CI, 1.20-1.28]), and depression (RR, 1.13; 95% CI, 1.09-1.17). Conclusions and Relevance The findings of this cohort study suggest that home time offers a patient-centered measure of post-ED outcomes for individuals with dementia. Future work should refine its application, particularly regarding the ED disposition decision, to better evaluate the long-term impact of ED care decisions.

Purpose: Irreversible corneal blindness disproportionately affects low- and middle-income countries where there remains a critical demand for surgeons skilled in corneal transplantation. Penetrating keratoplasty (PK) is a critical skill for ophthalmologists, especially as it remains the most widely performed type of corneal transplant in these parts of the world. Tools to teach and assess trainees in corneal transplantation are needed to help standardize training internationally. Here, we present an Ophthalmology Surgical Competency Assessment Rubric (OSCAR) aimed at assessing the competence and progress of residents in PK. Methods: A team of cornea specialists developed a rubric for PK using previously published OSCARs as a template. The draft included 11 key steps of PK and six global indices, with a grading scale based on a modified Dreyfus model. The rubric was then reviewed for face and content validity by a panel of eight international experts using an iterative feedback process. The draft underwent multiple cycles of feedback and revisions until a consensus was reached among the authors and the international expert panel. Results: The rubric contains 11 essential steps and six global indices with descriptions of expected functioning at four levels of competency (novice, beginner, advanced beginner, and competent). Conclusions: This OSCAR for PK contributes to the global standardization of ophthalmology training, helping to meet the increasing demand for corneal transplant services with high-quality care for all.