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This article presents modes of participation associated with a successful territorial implementation of a palliative care integrated services network as perceived by the diverse groups of stakeholders involved. A qualitative case study was performed in Quebec, Canada, using individual (n = 16) and group (n = 16) interviews, with a total of 106 participants. The analyses were based on the frameworks of Giddens and Patton. From a content analysis, a typology of six interconnected modes of participation at different levels of action emerged: territorial partnership, intraorganizational and interorganizational cooperation, interprofessional collaboration, community contribution, family commitment, and patient involvement. The interplay of the actors involved in different contexts was perceived by the participants as essential to improve accessibility, continuity, and quality of palliative care and the successful implementation of an integrated services network. The role of nonprofessionals is rarely taken into account in the functioning of healthcare systems. [ABSTRACT FROM AUTHOR]

Background: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots., Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee., Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot., Conclusions: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578., Competing Interests: Dr Nogueira: consulting for Anaconda, Medtronic, Cerenovus, Genentech, Viz-AI, Stryker, Prolong Pharmaceuticals, Perfuze, Biogen, Shanghai Wallaby, Brainomix, Hybernia, RapidPulse, Imperative Care, Corindus, NeuroVasc Technologies, Vesalio, Cerebrotech, Phenox, Astrocyte, Ceretrieve, Philips; grants from Stryker, Cerenovus; data safety monitoring for Synchron; ownership/investment interest in Ceretrieve, Corindus, Brainomix, Perfuze, Truvic, Viz-AI, Reist, Q’Apel, Vesalio, Cerebrotech, Viseon, Piraeus, Brain4Care, Quantanosis-AI. Dr Andersson: consulting for Neuravi, Anaconda, Johnson & Johnson (J&J), Rapid Medical; ownership/investment interest in Ceroflo. Dr Haussen: consulting for Brainomix, Vesalio, Stryker, Poseydon, Chiesi, Cerenovus; ownership/investment interest in Viz-AI; data safety monitoring for Jacobs Institute. Dr Yoo: consulting for Philips, Nicolab, ZOLL Circulation, Vesalio, Rapid Medical; grants and consulting for J&J, Medtronic, Penumbra; grants from Stryker, Genentech; ownership/investment interest in Gravity, Galaxy Therapeutics, Insera, Nicolab; data safety monitoring for NIH; employment with HCA Healthcare; other services for AHA. Dr Hanel: consulting for Balt, MicroVention, Medtronic, Rapid Medical, Stryker, Phenox, Cerenovus, Q’Apel; ownership/investment interest in Cerebrotech, Three Rivers Medical, NTI, Endostream, BlinkTBI, RisT, InNeuroCo, Corindus, eLum, Scientia. Dr Zaidat: consulting for J&J; patent holder. Dr Hacke: consulting for J&J. Dr Jovin: consulting for Contego Medical; grants from Medtronic, Stryker; employment with Cooper University Healthcare; data safety monitoring for Cerenovus; ownership/investment interest in Anaconda, StataDx, Galaxy, Basking, Freeox Biotech, Kandu, Viz-AI, Route92, Gravity. Dr Fiehler: consulting for Stryker, Cerenovus, Penumbra, MicroVention, Roche, Tonbridge, Phenox, TG Medical, Medtronic, Acandis; ownership/investment interest in Vastrax, Eppdata, Tegus; employment with Eppdata. Dr De Meyer: travel support from J&J. Dr Brinjikji: consulting for Cerenovus, MicroVention, Medtronic, Balt, Imperative Care, MIVI; ownership interest in Piraeus, Nested Knowledge, MIVI; research funding from Cerenovus, Brainomix, NIH. Dr Doyle: grants from SFI, Cerenovus. Dr Kallmes: grants from MIVI, Cerenovus, Balt, Vesalio, Stryker, MicroVention, Insera, Medtronic, Brainomix; ownership/investment interest in Superior Medical Experts, Conway Medical, Piraeus, Monarch Biosciences, Marblehead, Nested Knowledge; patent holder. Dr Liebeskind: consulting for Cerenovus, Medtronic, Genentech, Stryker, Rapid Medical. Dr Virmani: grants from Endotronix, L&J Bio, W.L. Gore, Recombinetics, Transverse Medical, Profusa, Lutonix, MicroVention, Envision, Neovasc, Cerus EndoVascular, MedAlliance, Interface Biologics, Biotronik, Mercator MedSystems, Spectrawave, Cook Medical, SoundPipe, Ossio, Bolt Medical, CardioMech, Olympus, Spartan Micro, Intact Vascular, Inc, Whiteswell, Vascudyne, Imperative Care, Biotyx Medical, SMT, Innovative Medical Devices, Cardiovascular Solutions, Dexcom, Emboline, Cooper Health, Children’s National, Concept Medical, Filterlex, eLum Technologies, Protembis, Boston Scientific, Polares, MDS, CeloNova, UCSF Foundation, Croivalve, Canon, Terumo, BD Biosciences, Limflow, Renata, Vetex, Recor, Mayo Clinic, CSI, Ohio Health, UPMC, Regencor, Vesper, Ripple Therapeutics, Polyvascular, Invatin, Innovative Cardiovascular Solutions, TruLeaf, Coramaze, ProKidney, 480 Biomedical, Transmural Systems, Intershunt Technologies, Pi-Cardia, Lyra Therapeutics, Sanofi, Phenox, Qool Therapeutics, Chansu Vascular Technologies, Nyra Medical, Surmodics, Microport, Leducq Foundation, OrbusNeich, Cardiac Implants, Rush University, Edwards Lifesciences, Cardionomic, Restore Medical, Medanex, CRL, Lahav, Pulse Biosciences, Jacobs Institute, Nova Vascular, Nephronyx, Maywell, Innovalve, Elucid Bioimaging, Medtronic, Biosensors International Group, ShockWave Medical, Cardiawave, NIH, Occlutech; consulting for Terumo, Recor Medical, Sino Medical, Medtronic, Cook, W.L. Gore, CSI, Surmodics, CeloNova, Edwards Lifesciences, BARD, Xeltis; other services for Xeltis, Medtronic; employment with CVPath Institute. Dr Kokoszka: employment with Cerenovus. Dr Inoa: consulting for Siemens, Viz-AI, Medtronic, Cerenovus, MicroVention, Penumbra; grants from Medtronic; employment with Semmes Murphey Clinic. Dr Humphries: consulting for Cerenovus. Dr Jabbour: consulting for Medtronic. Dr François: consulting for iVascular. Dr Levy: consulting for Guidepoint, GLG Consulting, Clarion, StimMed, Mosaic; other services for Penumbra, Medtronic, MicroVention; ownership/investment interest in Imperative Care, StimMed, Three Rivers Medical, NeXtGen Biologics, Q’Apel, Claret Medical, Rapid Medical. Dr Dashti: consulting for MicroVention, J&J, Cerenovus. Dr Schirmer: consulting for Balt, Medtronic, Stryker, Viz-AI, MicroVention; grants from Route92, MicroVention, Penumbra, Cerenovus, Balt, MIVI, Medtronic; employment with Geisinger; other services for Werfen, Cerenovus, NIH, Stryker, Neurotechnology Investors; ownership interest in Reist. Dr Hussain: consulting for J&J. Dr De Leacy: consulting for J&J, Imperative Care, Stryker; ownership/investment interest in Vastrax, Q’Apel, Spartan Micro, Synchron, Endostream. Dr Puri: consulting for J&J, MicroVention, Merit Medical, Stryker, Medtronic, Balt. Dr Chitale: grants, consulting, and data safety monitoring for Medtronic; grants from J&J. Dr Siddiqui: consulting for Cerebrotech, Boston Scientific, Rapid Medical, Cordis, W.L. Gore, Peijia Medical, Corindus, StimMed, J&J, Viz-AI, Silk Road Medical, Piraeus, Medtronic, Penumbra, Hyperfine Operations, Cerenovus, Endostream, Minnetronix Neuro, Stryker, Canon Medical Systems, Integra LifeSciences, Imperative Care, Apellis, Amnis Therapeutics, Vassol, IRRAS, Cardinal Health 200, Q’Apel, InspireMD, MicroVention, Serenity Medical; grants from Brain Aneurysm Foundation, NIH; other services for Rapid Medical, MicroVention, MIVI, Medical University of South Carolina, Penumbra, Cerenovus, InspireMD, Medtronic; ownership/investment interest in Willow Medtech, Cognition Medical, Whisper Medical, Spinnaker, Sim & Cure, Hyperion, BlinkTBI, Surgical, Inc, Radical Catheter Technologies, Imperative Care, Code Zero Medical, E8, Truvic, Tulavi, Bend IT, Neurolutions, Q’Apel, Endostream, Cerebrotech, Instylla, Collavidence Medical, Sense Diagnostics, Neurotechnology Investors, Peijia Medical, Synchron, Viseon, Borvo, E8, Galaxy Therapeutics, Piraeus, Adona Medical, NeuroRadial Technologies, NextGen Biologics, Viz-AI, Three Rivers Medical, StimMed, Serenity Medical, Cerevatech, Cvaid, Silk Road Medical, PerFlow Medical, InspireMD, VICIS, QAS.ai, SongBird, Launch NY, Neurovascular Diagnostics, Vastrax, Cognition Medical, Integra LifeSciences, Medtronic; employment with University at Buffalo Neurosurgery, Jacobs Institute; patent holder. The other authors report no conflicts.

Objectives: Explore whether extracorporeal cardiopulmonary resuscitation (ECPR) mortality differs by in-hospital cardiac arrest location and whether moving patients for cannulation impacts outcome., Design: Retrospective cohort study., Setting: ECPR hospitals that report data to the Extracorporeal Life Support Organization (ELSO)., Patients: Patients having ECPR for in-hospital cardiac arrest between 2020 and 2023 with data in the ELSO registry., Interventions: None., Measurements and Main Results: Patient demographics, comorbidities, pre-cardiac arrest conditions, pre-ECPR vasopressor use, cardiac arrest details, ECPR cannulation information, major complications, and in-hospital mortality were recorded. Multivariable logistic regression model was used to examine the associations between in-hospital mortality and 1) cardiac arrest location and 2) moving a patient for ECPR cannulation. A total of 2515 patients met enrollment criteria. The adjusted odds ratio (aOR) for mortality was increased in patients who had a cardiac arrest in the ICU (aOR, 1.85; 95% CI, 1.45-2.38; p < 0.001) and in patients who had a cardiac arrest in an acute care bed (aOR, 1.68; 95% CI, 1.09-2.58; p = 0.02) compared with the cardiac catheterization laboratory. Moving a patient for cannulation had no association with mortality (aOR, 0.70; 95% CI, 0.18-2.81; p = 0.62). Advanced patient age was associated with increased mortality. Specifically, patients 60-69 and patients 70 years old or older were more likely to die compared with patients younger than 30 years old (aOR, 1.71; 95% CI, 1.17-2.50; p = 0.006 and aOR, 2.27; 95% CI, 1.49-3.48; p < 0.001, respectively)., Conclusions: ECPR patients who experienced cardiac arrest in the ICU and in acute care hospital beds had increased odds of mortality compared with other locations. Moving patients for ECPR cannulation was not associated with improved outcomes., Competing Interests: Dr. Mazzeffi received funding from Octapharma, Hemosonics, and NovoNordisk. Dr. Buchner disclosed off-label use of extracorporeal membrane oxygenation. Dr. Glance’s institution received funding from the National Institute of Aging and the National Institute of Nursing Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: Fluorodeoxyglucose PET/computed tomography (FDG PET/CT) is effective in detecting large vessel vasculitis. Digital PET cameras have improved spatial resolution compared with analog PET, resulting in more prominent physiological uptake in arterial walls. This study's goal was to define qualitative normal variants of arterial activity on digital PET/CT., Methods: We retrospectively reviewed 126 oncological PET/CT studies. Exclusion criteria included history of vasculitis, immunosuppressant therapy, hyperglycemia, or altered FDG biodistribution. Qualitative vessel wall activity (common carotid, brachiocephalic, subclavian, aorta, and femoral) was visually graded by two nuclear physicians with guideline-proposed criteria: 0: ≤mediastinum, 1: liver, where grade 3 is compatible, 2 is possible, and <2 is negative for vasculitis. Cranial artery uptake was visually graded as follows: grade 0: ≤surrounding tissues, grade 1: just above surrounding tissues, and grade 2: significantly above surrounding tissues, with grades 1 and 2 considered positive for cranial artery vasculitis., Results: Large vessel uptake was grade 3 in 0 subjects, grade 2 in four subjects (3%), grade 1 in 87 subjects (69%), and grade 0 in 35 subjects (28%). In studies acquired ≥75 min post-injection, 1/15 subjects had grade 2 uptake. Four subjects (3%) had grade 1 vertebral artery uptake. No subjects had temporal, maxillary, or occipital artery uptake., Conclusion: A minority of our subjects presented with grade 2 large vessel uptake, which was associated with longer uptake times, or grade 1 cranial artery uptake, which was associated with higher age and glycemia. These findings should be interpreted with caution in patients referred for suspected vasculitis, as they may represent normal variants on digital PET., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recent studies have demonstrated the benefit of early ablation in preventing the progression of atrial fibrillation (AF). Clinical practice has reflected this shift in AF management and no longer requires patients to fail antiarrhythmic drugs (AADs) before receiving ablation. However, there is limited evidence on outcomes with pulsed field ablation (PFA) as a first-line therapy. Examination of real-world data may shed light on clinical practices and the effectiveness of PFA with and without a prior history of AAD usage., Methods: EU-PORIA is an all-comer AF registry enrolling consecutive patients treated with the pentaspline PFA catheter at 7 high-volume centers in Europe. This subanalysis evaluates patients with a history of class I/III AAD use versus those with no documented history of class I/III AAD use (first-line patients). Patients with incomplete AAD history, long-standing persistent AF, and those undergoing a repeat ablation procedure were excluded. Patients were treated and followed based on institutional standard of care. Any episode of atrial tachycardia or AF lasting longer than 30 s was considered an arrhythmia recurrence., Results: Of 1233 patients enrolled in EU-PORIA, 1091 met the inclusion criteria (mean age, 66 years; 40% females; and persistent AF, 36%). Pulmonary vein isolation-only was used in 90% of the patients, and 10% received extra-PV ablation. Ablation as the first-line approach was chosen in 589 patients, and 502 patients had prior class I/III AAD use. In the first-line PFA group, paroxysmal AF was more frequent (68% versus 59%; P <0.001), and pulmonary vein isolation-only was more frequent (93% versus 86%; P <0.001). At 1-year follow-up, freedom from AF/atrial tachycardia recurrence was similar in the ablation-first versus the ablation after failed AAD group (78% versus 74%, respectively; P =0.076)., Conclusion: In this large real-world PFA registry, freedom from AF/atrial tachycardia recurrence after 1 year was similar in patients undergoing PFA as a first-line treatment and those with prior failed AAD therapy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05823818.

Objectives: Intubation is a common procedure in acute hypoxemic respiratory failure (AHRF), with minimal evidence to guide decision-making. We conducted a survey of when to intubate patients with AHRF to measure the influence of clinical variables on intubation decision-making and quantify variability., Design: Factorial vignette-based survey asking "Would you recommend intubation?" Respondents selected an ordinal recommendation from a 5-point scale ranging from "Definite no" to "Definite yes" for up to ten randomly allocated vignettes. We used Bayesian proportional odds modeling, with clustering by individual, country, and region, to calculate mean odds ratios (ORs) with 95% credible intervals (CrIs)., Setting: Anonymous web-based survey., Subjects: Clinicians involved in the decision to intubate., Interventions: None., Measurements and Main Results: Between September 2023 and January 2024, 2,294 respondents entered 17,235 vignette responses in 74 countries (most common: Canada [29%], United States [26%], France [9%], Japan [8%], and Thailand [5%]). Respondents were attending physicians (63%), nurses (13%), trainee physicians (9%), respiratory therapists (9%), and other (6%). Lower oxygen saturation, higher Fio2, noninvasive ventilation compared with high-flow, tachypnea, neck muscle use, abdominal paradox, drowsiness, and inability to obey were associated with increased odds of intubation; diagnosis, vasopressors, and duration of symptoms were not. Nurses were less likely than physicians to recommend intubation. Within a country, the odds of recommending intubation changed between clinicians by an average factor of 2.60; within a region, the same odds changed between countries by 1.56. Respondents from Canada (OR, 0.53; CrI, 0.40-0.70) and the United States (OR, 0.63; CrI, 0.48-0.84) were less likely to recommend intubation than respondents from most other countries., Conclusions: In this international, multiprofessional survey of 2294 clinicians, intubation for patients with AHRF was mostly decided based on oxygenation, breathing pattern, and consciousness, but there was important variation across individuals and countries., Competing Interests: Dr. Yarnell received funding from the Canadian Institutes of Health Research (CIHR) and the Interdepartmental Division of Critical Care Medicine at the University of Toronto trainee award. He reports grant funding from the JP Bickell Foundation. Dr. Bellani receives lecturing fees from Draeger Medical and consultancy fees from Flowmeter. Drs. Brochard and Mellado-Artigas received funding from Medtronic and Fisher & Paykel. Dr. Brochard’s institution received funding from Stimit, Vitalaire, Cerebra Health, Sentec, and Philips. Dr. Goligher received funding from Getinge, Heecap, Lungpacer, BioAge, Stimit, Vyaire, Drager, and Zoll; He received support for article research from the CIHR. Dr. Mellado-Artigas received funding from Merck (Sharp & Dohme). Dr. Yoshida received funding from the Ministry of Education, Culture, Sports, Science and Technology, Japan and the Japan Science and Technology Agency. Dr. Fowler is the H. Barrie Fairley Professor of Critical Care at the Interdepartmental Division of Critical Care Medicine, University of Toronto. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The link between palliative care and oncology must continue to develop, taking into account advances in treatment.Immune checkpoint inhibition (ICI) for metastatic melanoma is associated with different types of response, making it difficult to assess the benefits to the patient. Some clinical trials suggest a survival advantage of ICI even in the absence of an objective radiographic response. The aim of this study is to assess the impact of continuing ICI after progression of the disease on the overall survival (OS) in a cohort of final-line metastatic melanoma patients. Clinical data from 120 patients with metastatic melanoma were collected via Melbase, a French multicentric biobank, prospectively enrolling unresectable melanoma. Two groups were defined: patients continuing final-line ICI at progression (treated) and patients stopping ICI at progression (controls). The primary end-point is the OS from progression. Propensity score weighting was used to correct for indication bias. From the 120 patients, 72 (60%) continued ICI. Median OS from progression was 4.2 months [95% confidence interval (CI) 2.6-6.27] in the treated group and median OS was 1.3 months (95% CI 0.95-1.74) in the control group (P < 0.0001). The calculated hazard ratio was 0.20 (0.13-0.33). Continued ICI was discovered to have an association with a higher rate of hospitalization at the end of life; more treatments received in the last 15 days of life and less utilization of specialist palliative care. This study discovered that patients with metastatic melanoma show a significant decrease in the instantaneous probability of mortality when they continue with finale-line ICI after progression., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Stroke is the second leading cause of death worldwide, and exposure to particulate air pollution is now recognized as one of the major modifiable risk factors. However, air pollution can vary in terms of physicochemical composition and exposition specificities. Therefore, its relationships with stroke outcomes remain under intense investigation., Recent Findings: This review highlights, alongside particles, that short-term and long-term exposure to nitrogen dioxide (NO 2 ) and ozone is likely to be also linked to stroke-related morbidity and mortality. Moreover, air pollution may increase the risk of transitioning from a healthy status to incident stroke and morbimortality after stroke. Additionally, relationships may vary depending on the air pollution mixture (e.g., particle-related components, pollutant interactions), pollutant sources (e.g., traffic-related or not), stroke etiology (ischemic or hemorrhagic), or exposed individual's characteristics (e.g., age, sex, genetic predisposition, weight status). Nonlinear dose-response functions and short-term effect lags have been reported, but these features need further refinement., Summary: The relationship between stroke and air pollution is now well established. Nonetheless, future research should further consider the physicochemical properties of air pollutants, multiple exposures, and individual vulnerabilities. Moreover, advanced statistical methods should be more commonly used to better describe the relationship shapes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity. This study tested whether sevoflurane postconditioning would improve long-term neurologic deficit through increased formation of new vessels close to the hemorrhage area., Methods: Fifty-three animals were subjected to SAH or sham surgery with or without a 2-hour sevoflurane postconditioning (versus propofol anesthesia). Animal survival, including dropout animals due to death or reaching termination criteria, as well as neurologic deficit, defined by the Garcia score, were assessed 2 hours after recovery until postoperative day 14. On day 14, blood samples and brain tissue were harvested. Vessel density was determined by the number of cluster of differentiation 31 (CD31)-positive vessels, and activated glial cells by glial fibrillary acidic protein (GFAP)-positive astrocytes per field of view., Results: The survival rate for sham animals was 100%, 69% in the SAH-propofol and 92% in the SAH-sevoflurane groups. According to the log-rank Mantel-Cox test, survival curves were significantly different ( P = .024). The short-term neurologic deficit was higher in SAH-propofol versus SAH-sevoflurane animals 2 hours after recovery and on postoperative day 1 (propofol versus sevoflurane: 14. 6 ± 3.4 vs 15. 9 ± 2.7 points, P = .034, and 16. 2 ± 3.5 vs 17. 8 ± 0.9 points, P = .015). Overall complete recovery from neurologic deficit was observed on day 7 in both SAH groups (18. 0 ± 0.0 vs 18. 0 ± 0.0 points, P = 1.000). Cortical vascular density increased to 80. 6 ± 15.0 vessels per field of view in SAH-propofol animals (vs 71. 4 ± 10.1 in SAH-sevoflurane, P < .001). Activation of glial cells, an indicator of neuroinflammation, was assessed by GFAP-positive astrocytes GFAP per field of view. Hippocampal GFAP-positive cells were 201 ± 68 vs 179 ± 84 cells per field of view in SAH-propofol versus SAH-sevoflurane animals ( P < .001)., Conclusions: Sevoflurane postconditioning improves survival by 23% (SAH-sevoflurane versus SAH-propofol). The sevoflurane intervention could attenuate the early neurologic deficit, while the long-term outcome was similar across the groups. A higher vascular density close to the SAH area in the propofol group was not associated with improved outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: In acute stroke, diffusion-weighted imaging (DWI) is used to assess the ischemic core. Dynamic-susceptibility contrast perfusion magnetic resonance imaging allows an estimation of the oxygen extraction fraction (OEF), but the outcome of DWI lesions with increased OEF postrecanalization is unclear. This study investigated the impact of OEF on the fate of DWI lesions in patients achieving recanalization after thrombectomy., Methods: This was a retrospective analysis of the HIBISCUS-STROKE cohort (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke; NCT: 03149705), a single-center observational study that prospectively enrolled patients who underwent magnetic resonance imaging triage for thrombectomy and a day-6 T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging. Automated postprocessing of admission dynamic-susceptibility contrast perfusion magnetic resonance imaging generated OEF maps. At visual analysis, the OEF status within DWI lesions was assessed in comparison to the contralateral side and correlated with volume changes (difference of ischemic lesion between admission DWI and registered day-6 T2-FLAIR). At voxel-based analysis, recovered DWI regions (lesions present on the admission DWI but absent on the registered day-6 T2-FLAIR) and nonrecovered regions were segmented to extract semiquantitative OEF values., Results: Of the participants enrolled from 2016 to 2022, 134 of 321 (41.7%) were included (median age, 71.0 years; 58.2% male; median baseline National Institutes of Health Scale score, 15.0). At visual analysis, 46 of 134 (34.3%) patients had increased OEF within DWI lesions. These patients were more likely to show a reduction in ischemic lesion volumes compared with those without increased OEF (median change, -4.0 versus 4.8 mL; P <0.0001). Multivariable analysis indicated that increased OEF within DWI lesions was associated with a reduction in ischemic lesion volumes from admission DWI to day-6 T2-FLAIR (odds ratio, 0.68 [95% CI, 0.49-0.87]; P =0.008). At voxel-based analysis, recovered DWI regions had increased OEF, while nonrecovered regions had decreased OEF (median, 126.9% versus -27.0%; P <0.0001)., Conclusions: Increased OEF within hyperacute DWI lesions was associated with ischemic lesion recovery between admission DWI and day-6 T2-FLAIR in patients achieving recanalization after thrombectomy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03149705., Competing Interests: None.

Background: The Resection And Partial Liver Transplantation with Delayed total hepatectomy (RAPID) procedure involves left hepatectomy with orthotopic implantation of a left lobe and right portal vein ligation. This technique induces volumetric graft increase, allowing for a right completion hepatectomy within 15 days. Notably, there is a lack of data on the hemodynamics of small-for-size grafts exposed to portal overflow without triggering small-for-size syndrome., Methods: A prospective single-center protocol included 8 living donors and 8 RAPID noncirrhotic recipients. Comprehensive clinical and biological data were collected, accompanied by intraoperative arterial and portal flow and pressure measurements. Early kinetic growth rate (eKGR%) and graft function were assessed using computed tomography and 99Tc-mebrofenin scintigraphy on postoperative days 7 and 14. Findings were compared with retrospective data from 13 left living donor liver transplantation (LDLT) recipients., Results: The median Graft-body weight ratio was 0.41% (interquartile range: 0.34-0.49), markedly lower than in LDLT. However, there was no significant difference in eKGR between RAPID and LDLT grafts. Sequential analysis revealed variable eKGR per day: 10.6% (7.8-13.2) in the first week and 7.6% (6-9.1) in the second week posttransplantation. Indexed portal flow (indexed portal vein flow) was significantly higher in RAPID compared with left LDLT ( P = 0.01). No hemodynamic parameters were found to correlate with regeneration speed. We modulated portal flow in 2 out of 8 cases., Conclusions: This study presents the first report of hemodynamic and volumetric data for the RAPID technique. Despite initial graft volumes falling below conventional LDLT recommendations, the study highlights acceptable clinical outcomes., Competing Interests: L.C. was supported by a grant from the Fondation Saint Luc. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Introduction: The maximal norepinephrine (NE) dose >1 μg/kg/min during circulatory shock apparently is associated with higher mortality, but this threshold needs confirmation. This study aimed at investigating whether NE infusion at a dose >1 μg/kg/min could predict early intensive care unit (ICU) mortality (first 5 days). The secondary objective was to assess the day-by-day relationship between NE dose during the first 4 days of ICU stay and subsequent mortality. Methods: We conducted a retrospective analysis of data from ICU patients receiving NE for circulatory shock at the Nimes University Hospital (France) from January 2016 to December 2019. Results: A total of 5,735 patients were admitted, 3,693 were screened, and 3,423 were analyzed. NE infusion at a dose >1 μg/kg/min was associated with day-5 mortality (hazards ratio: 7.40, P < 0.0001). The area under the receiver operating characteristic was 0.79 to predict day-5 mortality in ICU for maximal NE >1 μg/kg/min. The calculated threshold of 1.13 μg/kg/min for maximal NE was the best prognostic value (sensitivity: 67%, specificity: 80%, positive predictive value: 45%). When the 1.2 μg/kg/min threshold was crossed either on the first, second, third, or fourth day of ICU stay, the probability of subsequent death was 47%, 49%, 60%, and 40%, respectively. Along the first 4 days of ICU stay, the risk of death increased with increasing NE infusion dose. Conclusions: An NE infusion rate >1.13 μg/kg/min predicts day-5 mortality in ICU patients with circulatory shock. The time to reach maximal NE infusion rate was shorter in survivors than in nonsurvivors., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Purpose: To compare two drainage techniques in macula-off retinal detachment surgery: perfluorocarbon liquid (PFCL)-assisted drainage and partial subretinal fluid drainage without PFCL. This study investigated morphological and functional outcomes, focusing on metamorphopsia quantification., Methods: Eighty eyes with macula-off retinal detachment were retrospectively included. All underwent a 25-gauge pars plana vitrectomy. In the PFCL group, subretinal fluid drainage was performed using PFCL. In the partial subretinal fluid drainage (SRFD) group, subretinal fluid was partially drained through a preexisting retinal break without PFCL. A follow-up at 3 months and 6 months evaluated anatomical outcomes using optical coherence tomography, best-corrected visual acuity, and metamorphopsia quantified with M-charts., Results: Reattachment rates were comparable in the PFCL group (97.5%) and the SRFD group (95%) ( P > 0.05). Mean best-corrected visual acuity (logMAR) was 0.23 ± 0.32 (PFCL group) and 0.15 ± 0.13 (SRFD group) ( P = 0.206). Metamorphopsia was reported by 19 patients (47.5%) in the PFCL group and by 12 patients (30%) in the SRFD group ( P = 0.332). The mean metamorphopsia score was similar in both groups (0.27 ± 0.12 in the PFCL group and 0.28 ± 0.11 in the SRFD group, P = 0.866). Morphological optical coherence tomography findings were comparable in both groups., Conclusion: Morphological and functional outcomes were similar in PFCL and SRFD groups. Metamorphopsia quantification scores did not improve with PFCL. While both of these techniques might be effective and could be recommended for primary macula-off retinal detachment management, potential PFCL toxicity should be kept in mind and its use dedicated to selected cases., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Objective: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases., Background: Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management., Methods: We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers., Results: From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n=1203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates ( P =0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio =0.64; P =0.031) and incomplete resection (≥R1; hazard ratio=0.41; P =0.015)., Conclusions: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural course of COPD, as they increase morbidity and mortality. Acute pulmonary embolism may mimic the symptoms of COPD exacerbations. However, the exact prevalence of pulmonary embolism in unexplained exacerbations of COPD is unclear based on the current data. This review provides a practical approach to patients with COPD complaining of worsening respiratory symptoms., Recent Findings: A randomized clinical trial has shown that a routine pulmonary embolism diagnostic work-up does not improve care of patients with acute exacerbations of COPD. However, review of the recent literature suggests that a nonnegligible proportion of otherwise unexplained exacerbations of COPD may be caused by pulmonary embolism. To date, nevertheless, there are limited studies developing and validating clinical models that might aid in the identification of patients requiring additional tests for the diagnosis of pulmonary embolism., Summary: Until new evidence becomes available, we believe that a routine diagnostic strategy for pulmonary embolism is not appropriate for patients with acute exacerbations of COPD. Recommendations for routine pulmonary embolism diagnostic work-up necessitate further development of prognostic models and conduct of clinical trials that assess important health outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Past observational studies have reported the association between patient-ventilator asynchronies and poor clinical outcomes, namely longer duration of mechanical ventilation and higher mortality. But causality has remained undetermined. During the era of lung and diaphragm protective ventilation, should we revolutionize our clinical practice to detect and treat dyssynchrony?, Recent Findings: Clinicians' ability to recognize asynchronies is typically low. Automatized softwares based on artificial intelligence have been trained to largely outperform human eyesight and are close to be implemented at the bedside. There is growing evidence that in susceptible patients, dyssynchrony may lead to ventilation-induced lung injury (or patient self-inflicted lung injury) and that clusters of such dyssynchronous events have the highest association with poor outcomes. Dyssynchrony may also be associated with harm indirectly when it reflects over-assistance or over-sedation. However, the occurrence of reverse triggering by means of low inspiratory efforts during passive ventilation may prevent diaphragm dysfunction and atrophy and be beneficial., Summary: Most recent evidence on the topic suggests that synchrony between the patient and the mechanical ventilator is a critical element for protecting lung and diaphragm during the time of invasive mechanical ventilation or may reflect inadequate settings or sedation. Therefore, it is a complex situation, and clinical trials are still needed to test the effectiveness of keeping patient-ventilator interaction synchronous on clinical outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Although rituximab failed to demonstrate a significant effect on disability progression in primary progressive multiple sclerosis (PPMS), ocrelizumab succeeded. Our main objective was to analyze confirmed disability progression (CDP) in a cohort of patients with PPMS treated with anti-CD20 therapies compared with a weighted untreated control cohort., Methods: This was a retrospective study using data from the French MS registry (Observatoire Français de la Sclérose En Plaques). We included patients with PPMS treated or never treated with anti-CD20 therapies from 2016 to 2021, with an Expanded Disability Status Scale score of ≤6.5 at baseline. The primary outcome was time to first CDP. The secondary outcomes were time to first relapse, MRI activity at 2 years, identification of risk factors associated with CDP, and serious infection incidence rates (IIRs). Each outcome was studied using an inverse probability of treatment weighting method. The outcomes were modeled using a weighted proportional Cox model for the time-to-event outcomes and by a logistic regression regarding the MRI activity., Results: A total of 1,184 patients (426 treated and 758 untreated) fulfilled the inclusion criteria. Median age (Q1-Q3) was 56 years (49.3-63.8), and 52.7% were female. Among treated patients, 295 received rituximab, whereas 131 received ocrelizumab. At baseline, anti-CD20-treated patients were younger (median 51.9 vs 58.6 years, Cohen d = 0.683) and had more active disease (54.5 vs 27.8%, Cohen d = 0.562). 91.6% were drug-naive at inclusion. In time to first CDP analysis, no statistical significance was observed (hazard ratio [HR], 1.13; 95% CI 0.93-1.36, p = 0.2113). In time to first relapse analysis, a nonsignificant trend toward fewer patients relapsing in the treated group was observed (HR 0.83; 95% CI 0.48-1.28, p = 0.0809). For MRI activity, no significant difference was found between the 2 groups. Risk factors associated with CDP in the treated group were male sex and MS duration. IIR was 6.67 (95% CI 3.12-14.25) per 100 person-years in the treated group vs 2.67 (95% CI 0.80-8.86) in the untreated group., Discussion: Time to first CDP was not different between anti-CD20 treated and untreated patients with PPMS. Although our study is retrospective and mainly included patients treated by rituximab, our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS., Classification of Evidence: This study provides Class III evidence that anti-CD20 therapy of previously untreated patients with PPMS was not superior to no therapy in delaying time to first CDP.

Purpose: To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse., Methods: This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group., Results: A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months., Conclusion: The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

Objectives: Unexpected accumulations of gadolinium in various organs were reported after the administration of gadolinium-based contrast agents, making desirable to reduce the dose while maintaining equivalent diagnostic performance. The aim of this study was to evaluate the contrast enhancement performance of high relaxivity gadopiclenol compared with gadoterate meglumine in abdominal contrast-enhanced magnetic resonance angiography (CE-MRA)., Materials and Methods: In a first study in healthy rabbits, axial 3D gradient echo sequences were applied at 4.7 T to study arterial enhancement as a function of gadopiclenol dose (0.025, 0.05, 0.075, and 0.1 mmol Gd/kg) or gadoterate meglumine at 0.1 mmol Gd/kg (n = 5-6/group). The increase in signal-to-noise ratio (ΔSNR) in the aorta at the first pass was measured and compared. In a second, crossover study in 6 healthy pigs, abdominal CE-MRA sequences were acquired at 3 T with gadopiclenol at 0.05 mmol Gd/kg or gadoterate meglumine at 0.1 mmol Gd/kg at a 1-week interval. Quantitatively on the maximum intensity projection (MIP) images, the mean MIP SNR within the aorta of both groups was compared. Qualitatively, a blinded comparison of the angiograms was performed by an experienced radiologist to determine the preferred contrast agent., Results: In the rabbit, ∆SNR is linearly correlated with the gadopiclenol dose ( P = 0.0010). Compared with gadoterate meglumine 0.1 mmol Gd/kg, an increase in the ∆SNR is observed after 0.05, 0.075, and 0.1 mmol Gd/kg of gadopiclenol (+63% P = 0.0731, +78% P = 0.0081, and +72% P = 0.0773, respectively), whereas at 0.025 mmol Gd/kg, ∆SNR is in the same range as with gadoterate meglumine 0.1 mmol Gd/kg (+15% P > 0.9999). In pigs, contrast enhancement after gadopiclenol at 0.05 mmol/kg is +22% superior to MIP SNR after gadoterate meglumine at 0.1 mmol Gd/kg ( P = 0.3095). Qualitatively, a preference was shown for gadopiclenol images (3/6) over the gadoterate meglumine examinations (1/6), with no preference being shown for the remainder (2/6)., Conclusions: First-pass CE-MRA is feasible with gadopiclenol at 0.05 mmol Gd/kg with at least the same arterial signal enhancement and image quality as gadoterate meglumine at 0.1 mmol Gd/kg., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Approximately 30% of people infected with COVID-19 require hospitalization, and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial., Methods: Fifty-nine patients (38-78 yr) hospitalized in ICU for COVID-19 infection for 32 (6-80) d, including 23 (3-57) d of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 d after discharge and was dedicated to questionnaires, blood sampling, and cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 d later., Results: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non-fatigued (i.e., 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 L vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in 1 s, respectively), and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82% ± 14% vs 91% ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression, and quality of life ( P < 0.05)., Conclusions: COVID-19 survivors showed altered respiratory function 4 to 8 wk after discharge, which was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e., sleep satisfaction, quality of life, or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue., (Copyright © 2024 by the American College of Sports Medicine.)

Snapping triceps syndrome is a rare cause of medial elbow pain and ulnar neuritis caused by subluxation and triggering of the medial tricipital muscle belly over the medial distal humeral ridge and condyle. The diagnosis and surgical management of snapping triceps syndrome can be challenging due to the subtlety of the symptoms and the infrequent presentation. Despite the diagnosis relying largely on clinical examination, noninvasive dynamic ultrasonography may facilitate detection. Correct recognition of this condition is crucial in the avoidance of surgical misadventure and revision surgery. This paper illustrates our surgical technique for the management of snapping triceps and reviews the available literature on this relatively obscure condition., Competing Interests: Conflicts of Interest and Source of Funding: The authors report no conflicts of interest and no source of funding., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes., Methods: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method., Results: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%., Discussion: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk., Classification of Evidence: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Background: Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients., Methods: This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland-Altman plots and Passing-Bablok regressions., Results: The Bland-Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%)., Conclusions: In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Background and Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive progressive neurodegenerative primary motor neuron disorder caused by biallelic variants of the survival motor neuron 1 ( SMN1 ) gene. The most recent SMA best practice recommendations were published in 2018 shortly after the approval of the first SMN-enhancing treatment. The availability of disease-modifying therapies for 5q SMA and implementation of SMA newborn screening (NBS) has led to urgency to update the SMA best practice recommendations for diagnosis and to reevaluate the current classification of SMA. In addition, the availability of disease-modifying therapies has opened the door to explore improved diagnosis of adult-onset SMA., Methods: A systematic literature review was conducted on SMA NBS. An SMA working group of American and European health care providers developed recommendations through a modified Delphi technique with serial surveys and virtual meeting feedback on SMA diagnosis to fill information gaps for topics with limited evidence. A community working group of an individual with SMA and caregivers provided insight and perspective on SMA diagnosis and support through a virtual meeting to guide recommendations., Results: The health care provider working group achieved consensus that SMA NBS is essential to include in the updated best practice for SMA diagnosis (100%). Recommendations for the following are described: characterizing NBS-identified infants before treatment; minimum recommendations for starting or offering SMA NBS in a state or country; recommendations for activities and services to be provided by an SMA specialty care center accepting SMA NBS referrals; and recommendations for partnership with individuals with SMA and caregivers to support NBS-identified infants and their caregivers. Limited data are available to advance efficient diagnosis of adult-onset SMA., Discussion: Updating best practice recommendations for SMA diagnosis to include SMA NBS implementation is essential to advancing care for individuals with SMA. In addition to testing, processes for the efficient management of positive newborn screen with access to knowledgeable and skilled health care providers and access to treatment options is critical to successful early diagnosis. Additional evidence is required to improve adult-onset SMA diagnosis., Competing Interests: M. Schroth is an employee of Cure SMA; J. Deans is an employee of Cure SMA; K. Arya reports no disclosures; D. Castro received research support from Biohaven, Genentech, and Biogen, served as a speaker for Novartis Gene Therapies, and served on the Cure SMA Board of Directors; D. De Vivo served on scientific advisory boards for Novartis Gene Therapies, Biogen, Ionis Pharmaceuticals, Inc., PTC Therapeutics, Roche, and the SMA Foundation, served as a consultant for Novartis Gene Therapies and Biogen, received research support from the SMA Foundation and Cure SMA, and received clinical trial funding from Biogen and Scholar Rock; M. Gibbons reports no disclosures; C. Ionita reports no disclosures; N.L. Kuntz served on a scientific advisory board for Genentech, and received institutional clinical trial research support from Biogen, Genentech, and Novartis Gene Therapies; A. Lakhotia received research support from Novartis Gene Therapies and Genentech and served on editorial board for Pediatric Neurology; E. Neil Knierbein reports no disclosures; M. Scoto served on scientific advisory boards and as a speaker for Roche, Novartis, and Biogen; T. Sejersen received research support from PTC Therapeutics and served as a consultant for Biogen, Novartis, PTC Therapeutics, and Roche and received ALF funding from Stockholm Regional Council and research funding to the Center for Neuromusculoskeletal Restorative Medicine from Health@InnoHK program launched by Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region of the People's Republic of China; L. Servais served as a consultant for Biogen, Roche, Novartis Gene Therapies, Biohaven, and Scholar Rock; C. Tian received clinical trial research support from Biohaven and Novartis Gene Therapies; M. Waldrop served on scientific advisory board for Novartis Gene Therapies and received clinical trial research support from Novartis Gene Therapies; J.F. Vázquez Costa served on scientific advisory boards and served as a speaker for Roche, Novartis, and Biogen and received research support from Roche. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment., Methods: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis., Results: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis., Conclusion: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy., Findings: In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis., Competing Interests: S.G. reported grants, personal fees, and nonfinancial support fomr IPSEN, Mylan, Mayoli, Novartis. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: CCR5, a G protein-coupled receptor (GPCR), is used by most HIV strains as a coreceptor. In this study, we looked for other GPCR able to modify HIV-1 infection., Design: We analyzed the effects of one GPCR coexpressed with CCR5, EBI2, on HIV-1 replicative cycle., Methods: We identified GPCR expressed in primary CD4 + CCR5 + T cells by multi-RT-qPCR. We studied GPCR dimerization by FRET technology. Cell lines expressing EBI2 were established by transduction with HIV vectors. HIV-1 entry was quantified with virions harboring β-lactamase fused to the viral protein vpr, early and late HIV-1 transcriptions by qPCR, NFkB nuclear activation by immunofluorescence and transfection, and viral production by measuring p24 concentration in culture supernatant by ELISA., Results: We showed that EBI2 is naturally expressed in primary CD4 + CCR5 + T cells, and that CCR5 and EBI2 heterodimerize. We observed that this coexpression reduced viral entry by 50%. The amount of HIV reverse transcripts was similar in cells expressing or not EBI2. Finally, the presence of EBI2 induced the translocation of NFkB and activated HIV-1 genome expression. Globally, the result was a drastic HIV-1 R5, but not X4, overproduction in EBI2 -transduced cells., Conclusion: EBI2 expression in CD4 + CCR5 + cells boosts HIV-1 R5 productive infection. As the natural ligand for EBI2 is present in blood and lymphoid tissues, the constant EBI2 activation might increase HIV replication in CD4 + T cells. It might be of interest to test the effect of EBI2 antagonists on the residual viral production persisting in patients aviremic under treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In recent years, osteoarthritis of the knee, a common degenerative joint disease, often occurs in the elderly population. This disease has a significant impact on the quality of life of patients. For treating knee osteoarthritis, physical therapy is highly regarded as a very effective treatment method. This article delves deeply into commonly used physical therapy methods and analyzes their therapeutic effects, cost-effectiveness, and applicability, aiming to find treatments with broader applicability and better cost-effectiveness. The goal is to help a large number of patients effectively alleviate the discomfort caused by knee osteoarthritis, enhance the clinical therapeutic effects, and introduce home treatment methods to reduce financial burdens. The article also compares various physical therapy methods and finds that moxibustion and electrotherapy are more suitable for home use. Other treatment methods provide a reliable scientific basis for patient treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS., Methods: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk., Results: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS ( p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04)., Conclusion: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Objective: To analyze the reasons for stopping pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivered for unresectable peritoneal surface malignancies (PSM) and to determine survival in a large patient cohort of an experienced PIPAC center., Background: PIPAC alone or combined with systemic chemotherapy was developed to palliatively treat unresectable PSM. Safety, tolerance and promising survival results were already reported, but the reasons for stopping treatment remain unclear and the influence of the number of PIPAC procedures on prognosis has not been evaluated., Methods: A retrospective analysis of PIPAC procedures from a prospectively maintained single institution PSM database was conducted from January 2016 to January 2023., Results: A total of 346 patients underwent 1200 PIPAC treatments in the defined time period. Two-thirds of the patients completed 3 or more PIPAC procedures, and 2 patients had more than 15 treatment procedures. Reasons for PIPAC cessation were disease progression or complication (56%), reorientation to a potential curative procedure (19%), surgical complications of the procedure (13%), death between procedures (8%) and patient request (3%). PSM origin and receiving 3 or more PIPAC treatments were independently correlated with better survival in the overall population, in the group of ultimately unresectable PSM and after propensity score weighting., Conclusion: The main reason for stopping PIPAC treatment in palliative management of PSM is disease progression. When 3 or more PIPAC procedures can be delivered in combination to systemic chemotherapy, survival is significantly improved. Its use should be validated by prospective studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Managing postoperative pain effectively with an opioid-free regimen following laparoscopic surgery (LS) remains a significant challenge. Intraperitoneal instillation of ropivacaine has been explored for its potential to reduce acute postoperative pain, but its efficacy and safety are still under debate. This study aimed to evaluate the efficacy and safety of intraperitoneal instillation of ropivacaine for acute pain management following laparoscopic digestive surgery., Methods: We used PRISMA 2020 and a measurement tool to assess systematic reviews 2 guidelines to conduct this review. The random-effects model was adopted using Review Manager Version 5.4 for pooled estimates., Results: We retained 24 eligible RCTs involving 1705 patients (862 patients in the intraperitoneal instillation group and 843 patients in the control group). The intraperitoneal instillation group reduced total opioid consumption during the first 24 hours postoperatively (MD = -21.93 95% CI [-27.64, -16.23], P < .01), decreased pain scores at different time (4 hours, 8 hours, 12 hours and 24 hours), shorter the hospital stay (MD = -0.20 95% CI [-0.36, -0.05], P < .01), reduced the postoperative shoulder pain (MD = 0.18 95% CI [0.07, 0.44], P < .01), and decreased postoperative nausea and vomiting (MD = 0.47 95% CI [0.29, 0.77], P < .01)., Conclusion: Intraperitoneal instillation of ropivacaine appears to be an effective component of multimodal pain management strategies following laparoscopic digestive surgery, significantly reducing opioid consumption and improving postoperative recovery markers. Despite these promising results, additional high-quality trials are needed to confirm the efficacy and safety of this approach., Registration: The registration number at PROSPERO was CRD42021279238., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA)., Methods: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FA out ) by measuring D-dimer levels at the blood-thrombus interface and inside (FA in ) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FA in , and FA out were determined by intravenous thrombolysis-adjusted linear regression., Results: FA out ( P <0.0001) and FA in ( P =0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FA out was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FA out was increased with cardioembolic thrombi (72/104), which are rich in fibrin ( P =0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit ( P =0.0139), and hemoglobin level ( P =0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FA out ( P =0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FA out was significantly associated with reduced thrombus weight ( P =0.0310), increased recanalization rate ( P =0.0150), good clinical outcome ( P =0.0480), and reduced mortality ( P =0.0080)., Conclusions: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies., Competing Interests: Disclosures None.

Bilevel-positive airway pressure (BiPAP) is a noninvasive respiratory support modality which reduces effort in patients with respiratory failure. However, it may increase tidal ventilation and transpulmonary pressure, potentially aggravating lung injury. We aimed to assess if the use of BiPAP before intubation was associated with increased mortality in adult patients with coronavirus disease 2019 (COVID-19) who received venovenous extracorporeal membrane oxygenation (ECMO). We used the Extracorporeal Life Support Organization Registry to analyze adult patients with COVID-19 supported with venovenous ECMO from January 1, 2020, to December 31, 2021. Patients treated with BiPAP were compared with patients who received other modalities of respiratory support or no respiratory support. A total of 9,819 patients from 421 centers were included. A total of 3,882 of them (39.5%) were treated with BiPAP before endotracheal intubation. Patients supported with BiPAP were intubated later (4.3 vs . 3.3 days, p < 0.001) and showed higher unadjusted hospital mortality (51.7% vs. 44.9%, p < 0.001). The use of BiPAP before intubation and time from hospital admission to intubation resulted as independently associated with increased hospital mortality (odds ratio [OR], 1.32 [95% confidence interval {CI}, 1.08-1.61] and 1.03 [1-1.06] per day increase). In ECMO patients with severe acute respiratory failure due to COVID-19, the extended use of BiPAP before intubation should be regarded as a risk factor for mortality., Competing Interests: Disclosure: None reported related to the present manuscript. D.B. receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. J.R. received honoraria for lecture and medical advisory from Gilead, Medtronic, and Werfen. He’s part of the ELSO Scientific Oversight Committee. A.C. reports grants and personal fees from Getinge, Xenios, and Baxter. R.P.B. is a member of the ELSO Executive Board and co-chair of PediECMO. L.B. received honoraria for a lecture from Fisher Paykel. G.B. received consulting fees from Flowmeter S.p.a. and an institutional grant from DIMAR S.r.l. The other authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers-i.e., changes over time-in the context of bleeding events in patients on ECMO., Methods: Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter., Results: The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin-antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin-antiplasmin, tPA, PAI-1, and tPA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. -440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049)., Conclusions: Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses normothermic regional perfusion (NRP), and involves short cold ischemia times (CIT) and constrained asystole times differing by donor age., Methods: Logistic regression identified risk factors for primary nonfunction (PNF), delayed graft function (DGF), and graft failure., Results: Risk factors for PNF included donor hypertension, admission for ischemic vascular stroke, and HLA DR mismatches. Risk factors for DGF included functional warm ischemia time >40 min, dialysis >2 y, recipient body mass index of 30 kg/m2 or higher, recipient diabetes, and CIT >10 h. Risk factors for 1-y graft failure included donor hypertension, donor lung recovery, ostial calcification, recipient cardiovascular comorbidities, and HLA DR mismatches. A high donor estimated glomerular filtration rate protected against DGF and graft failure at 1-y. After adjustment restricted to recipient and graft factors and donor age, the risks of PNF, DGF, and graft failure increased with donor age up to 65 y and then remained stable., Conclusions: The study suggests that cDCD kidney transplants are highly successful, but also that its outcomes are influenced by lung recovery, poor HLA DR matching, and warm ischemia times differing with donor age. Our study identified several risk factors for kidney transplantation failure after cDCD with systematic use of NRP and some of them seem as modifiable variables associated with cDCD transplant outcome., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Importance: Several studies reported that violent behaviours were committed by patients against healthcare professionals in emergency departments (EDs). The presence of mediators could prevent or resolve situations of tension., Objective: To evaluate whether the presence of mediators in EDs would have an impact on violent behaviours committed by patients or their relatives against healthcare professionals. Design, settings and participants A 6-period cluster randomised crossover trial was performed in 4 EDs during 12 months. Patients aged ≥18 and their relatives were included., Intervention: In order to prevent or resolve situations of tension and conflict, four mediators were recruited.Outcome measure and analysis Using a logistic regression mixed model, the rate of ED visits in which at least one act of violence was committed by a patient or their relatives, reported by healthcare professionals, was compared between the intervention group and the control group., Results: A total of 50 429 ED visits were performed in the mediator intervention group and 50 851 in the control group. The mediators reported 1365 interventions; >50% of the interventions were to answer questions about clinical management or waiting time. In the intervention group, 173 acts of violence were committed during 129 ED visits, and there were 145 acts of violence committed during 106 ED visits in the control group. The rate of ED visits in which at least one act of violence was committed, was 0.26% in the intervention group and 0.21% in the control group (OR = 1.23; 95% CI [0.73-2.09]); on a 4-level seriousness scale, 41.6% of the acts of violence were rated level-1 (acts of incivility or rudeness) in the intervention group and 40.0% in the control group., Conclusion: The presence of mediators in the ED was not associated with a reduction in violent or uncivil behaviours committed by patients or their relatives. However, the study highlighted that patients had a major need for information regarding their care; improving communication between patients and healthcare professionals might reduce the violence in EDs., Trial Registration: Clinicaltrials.gov (NCT03139110)., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020., Methods: This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected., Results: Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH ( p = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH ( p = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, p = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up., Discussion: This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned., Classification of Evidence: This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort., Competing Interests: F. Trucco reports participation to Scientific Advisory Boards for Roche UK and teaching initiatives for Biogen, Avexis, Roche, and BREAS. D. Ridout, I. Hughes, Z. Zolkipli-Cunningham, and M. Main report no disclosures. M. Scoto reports participation in Scientific Advisory Boards and teaching initiatives for Avexis, Biogen, and Roche. She is involved as an investigator in clinical trials from Avexis, Biogen, and Roche. In addition, she is the co-principal investigator of the SMA REACH UK clinical network, partially funded by Biogen and Roche. F. Muntoni reports participation in Scientific Advisory Boards and teaching initiatives for Biogen, Roche, and Novartis. He is member of the Rare Disease Scientific Advisory Board for Pfizer. He is involved as an investigator in clinical trials from Novartis, Biogen, and Roche. In addition, he is the principal investigator of the SMA REACH UK clinical network, partially funded by Biogen and Roche. E. Mercuri reports participation in Scientific Advisory Boards and teaching initiatives for Biogen, Roche, Scholar Rock, and Novartis. He is involved as an investigator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. In addition, he is the principal investigator of the Italian registry participating in iSMAc, partially funded by Biogen, Roche, and Novartis. R. Finkel reports participation in Medical and Scientific Advisory Boards on SMA topics with Novartis, Biogen, Ionis, Roche, Cure SMA, SMA Europe, SMA REACH UK, SMA Foundation, and MDA. Finkel participates as an investigator in SMA-related clinical trials sponsored or supported by Novartis, Biogen, Ionis, Roche, and Scholar Rock. Dr. D. De Vivo reports participation as a consultant in Medical and Scientific Advisory Boards and as an investigator with Novartis, Biogen, Ionis, Roche, PTC, Santhera, Scholar Rock, Sanofi, GliaPharm, Fulcrum Therapeutics, Sarepta, NS Pharma, SMA Foundation, Cure SMA, DoD, NIH, Glut1 Deficiency Foundation, and Hope for Children Research Foundation. B. Darras has served as an ad hoc Scientific Advisory Board member for Novartis, Biogen, Cytokinetics, Vertex, Genentech, Roche, and Sarepta; Steering Committee chair for Roche; and Data Safety Monitoring Board member for Amicus Inc. He has no financial interests in these companies. He has received research support from the NIH/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, the Spinal Muscular Atrophy Foundation, CureSMA, and Working on Walking Fund and has received grants from Ionis Pharmaceuticals, Inc, for the ENDEAR, CHERISH, CS2/CS12 studies; from Biogen for CS11; and from Cytokinetics, Sarepta Pharmaceuticals, PTC Therapeutics, Fibrogen, and Summit. O. Mayer reports participation in Advisory Boards for Roche, Biogen, and PTC Therapeutics. He is participating in SMA REACH and iSMAC, partially funded by Biogen. C. Bruno reports participation in Scientific Advisory Boards on SMA topics with Novartis, Biogen, and Roche and participates as a principal investigator in SMA-related clinical trials sponsored by Novartis, Biogen, Ionis, and Roche. S. Messina reports participation in Scientific Advisory Boards and teaching initiatives for Novartis, Biogen, and Roche. She is involved as an investigator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. M. Pane reports participation in Scientific Advisory Boards and teaching initiatives for Novartis and Biogen. V.A. Sansone provides intellectual support in Advisory Boards and teaching activities for Biogen, Santhera, Sarepta, PTC, Dyne, Triplet, and Novartis. A. D'Amico reports participation in Scientific Advisory Board for Novartis, Roche, and Novartis and teaching initiatives for Biogen. She is also involved as an investigator in clinical trials from Novartis, Biogen, and Roche. In addition, she is an investigator of the Italian registry participating in iSMAc, partially funded by Biogen. E.S. Bertini reports participation in Scientific Advisory Boards for Novartis, Roche, Novartis, and PTC and teaching initiatives for Biogen. He is also involved as an investigator in clinical trials from Novartis, Biogen, Roche, and Novartis. In addition, he is an investigator of the Italian registry participating in iSMAc, partially funded by Biogen. C. Marini-Bettolo reports participation in Scientific Advisory Boards and teaching initiatives for Novartis, Biogen, and Roche. She is involved as an investigator in clinical trials from Novartis. In addition, she is principal investigator for the UK SMA patient registry funded by SMA UK. A. Childs reports participation in Advisory Boards for Novartis, Roche, Biogen, Santhera, and PTC Therapeutics. She is principal investigator for clinical trials supported by Sarepta, Santhera, and PTC Therapeutics. She is participating in SMA REACH and iSMAC, partially funded by Biogen. M. Ong reports participation in Advisory Boards or received consultation fees for Novartis, Roche, Biogen, and CSL Behring. She is participating in SMA REACH and iSMAC, partially funded by Biogen. Dr. A. Mayhew reports participation in Scientific Advisory Boards and teaching initiatives for Biogen and Roche. She is involved as an evaluator at site and acts as an independent consultant to train evaluators in clinical trials from Novartis, Biogen, and Roche. In addition, she is the principal investigator at Newcastle for the SMA REACH UK clinical network, partially funded by Biogen and by SMA UK. J. Montes reports participation as a consultant and on Scientific Advisory Boards for Biogen, Ionis, Roche, and Scholar Rock. G. Coratti reports consultant activities for Novartis, Biogen, Roche, Biologix, and Genesis Pharma. She is involved as a clinical evaluator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. R. De Sanctis reports consultant activities for Biogen and Roche. He is involved as a clinical evaluator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. L. Servais reports consultancy/board attendance/lectures for Novartis, Biogen, Roche, Scholar Rock, and BioHaven. A. Majumdar reports participation in Advisory Boards for Novartis, Roche, Biogen, Santhera, and PTC Therapeutics. He is principal investigator for clinical trials supported by Wave Therapeutics. He is participating in SMA REACH and iSMAC, partially funded by Biogen. D. Parasuraman reports participation in Advisory Boards for Roche, Biogen, Sarepta and has had support from PTC Therapeutics. He is principal investigator for clinical trials supported by Roche. He is participating in SMA REACH and iSMAC, partially funded by Biogen. V. Gowda reports participation in Advisory Boards or received consultation fees for Novartis, Roche, Biogen, PTC therapeutics, Wave Life Sciences, Pfizer, and Sarepta Therapeutics. She is participating in SMA REACH and iSMAC, partially funded by Biogen. FT, CB, EB, AD, EM, and MP are members of the ERN NMD (European Reference Networks). Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center. The response of CNS lesions to second-line triple therapy was assessed through monthly clinical and at least quarterly morphological (according to RECIST criteria) evaluation. Tolerance data were also collected. Seventeen patients were included with a mean follow-up of 2.59 (±2.43) months. Only 1 patient displayed a significant clinical and morphological response. No statistically significant difference was observed between patients receiving or not additional local therapy (mainly radiotherapy) as to response achievement. Immunotherapy was permanently discontinued in 1 patient owing to grade 4 toxicity. Mean PFS and OS after CNS progression were 2.59 and 4.12 months, respectively. In this real-life survey, the subsequent addition of anti-PD1 to combined targeted therapy in melanoma patients with upfront CNS metastases did not result in significant response of CNS targets in most BRAF mutated melanoma patients with secondary CNS progression after initially successful first-line combined targeted therapy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Nivolumab was first authorized at a weight-based dose (WBD) of 3 mg/kg every two weeks (Q2W). Since 2017, a fixed dose (FD) regimen [first 240 mg Q2W and then 480 mg per month (Q4W)] was allowed. The objective of the study was to compare a WBD regimen and an FD regimen with regard to effectiveness and safety. We conducted a single-center, retrospective, real-life study of consecutive adult patients who had received a WBD of nivolumab or an FD of 480 mg Q4W. The primary endpoint was the occurrence of grade ≥3 immune-related adverse events (irAEs). The secondary endpoints were overall survival and cost of the treatment. In all, 342 patients were included: 71 in the WBD cohort and 271 in the FD cohort. Of these patients, 201 patients (59.6%) experienced an irAE, and 24 of these events were graded as ≥3. At 12 months, there was no significant difference in irAE occurrence between the two cohorts [hazard ratio (95% confidence interval): 0.54 (0.21-1.36), P  = 0.19]. The 12-month overall survival rate was significantly lower in the WBD cohort ( P  < 0.001). Switching from a fortnightly weight dose to a fixed monthly dose halves the cost of hospitalization. Our results did not show a significant difference between WBD and FD cohort in the occurrence of severe irAEs. However overall survival appeared to be significantly higher in FD group. Some clinical trials are investigating a hybrid dosing regimen in which a WBD is capped by an FD. The present results need to be confirmed in prospective studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Impaired cognition is a major predisposing factor for postoperative delirium, but it is not systematically assessed. Anesthesia and surgery may cause postoperative delirium by affecting brain integrity. Neurofilament light in serum reflects axonal injury. Studies evaluating the perioperative course of neurofilament light in cardiac surgery have shown conflicting results. The authors hypothesized that postoperative serum neurofilament light values would be higher in delirious patients, and that baseline concentrations would be correlated with patients' cognitive status and would identify patients at risk of postoperative delirium., Methods: This preplanned secondary analysis included 220 patients undergoing elective cardiac surgery with cardiopulmonary bypass. A preoperative cognitive z score was calculated after a neuropsychological evaluation. Quantification of serum neurofilament light was performed by the Simoa (Quanterix, USA) technique before anesthesia, 2 h after surgery, on postoperative days 1, 2, and 5. Postoperative delirium was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method, and a chart review., Results: A total of 65 of 220 (29.5%) patients developed postoperative delirium. Delirious patients were older (median [25th percentile, 75th percentile], 74 [64, 79] vs. 67 [59, 74] yr; P < 0.001) and had lower cognitive z scores (-0.52 ± 1.14 vs. 0.21 ± 0.84; P < 0.001). Postoperative neurofilament light concentrations increased in all patients up to day 5, but did not predict delirium when preoperative concentrations were considered. Baseline neurofilament light values were significantly higher in patients who experienced delirium. They were influenced by age, cognitive z score, renal function, and history of diabetes mellitus. Baselines values were significantly correlated with cognitive z scores (r, 0.49; P < 0.001) and were independently associated with delirium whenever the patient's cognitive status was not considered (hazard ratio, 3.34 [95% CI, 1.07 to 10.4])., Conclusions: Cardiac surgery is associated with axonal injury, because neurofilament light concentrations increased postoperatively in all patients. However, only baseline neurofilament light values predicted postoperative delirium. Baseline concentrations were correlated with poorer cognitive scores, and they independently predicted postoperative delirium whenever patient's cognitive status was undetermined., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH., Methods: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation., Results: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years., Conclusions: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted., Competing Interests: Disclosures Dr Anderson has received sponsored research support from Bayer AG and has consulted for ApoPharma unrelated to this work. Dr Rosand reports compensation from National Football League and Takeda Development Center Americas for consultant services, unrelated to this work. The other authors report no conflicts.

Pan-negative melanomas account for 30% of melanomas. In case of immunotherapy failure, therapeutic options are limited. Oncogene fusions represent a target of interest in many solid cancers. In melanoma, the frequency of oncogene fusion is not well documented and not routinely investigated. We conducted a single-center retrospective study. The objective was to determine the frequency of oncogene fusion detected by RNA sequencing, in patients with advanced or metastatic pan-negative melanoma. In parallel, an extended molecular alteration search was performed using extended targeted next-generation sequencing. We identified 59 patients with advanced pan-negative melanoma between January 2021 and January 2023. It was a cutaneous melanoma in 71.1% of the cases, a mucous melanoma in 15.2% of the cases. We identified nine patients with a RAF fusion, including seven BRAF gene fusion and two RAF1 fusion. Of the other molecular alterations, NF1 mutation was the most frequent molecular alteration identified. Among the nine patients with RAF fusions, all the patients initially received treatment with anti-PD1 ± anti-CTLA4 immunotherapy. After immunotherapy failure, five patients benefited from second-line targeted therapy (two with BRAF and MEK inhibitors combination, three MEK inhibitors alone). The response rate was 20%. In a population of pan-negative melanoma, we detected 15.2% of RAF fusion. Fusion detection allowed the introduction of a second line of targeted therapy, in the absence of a validated therapeutic option in 55.5% of cases. This study suggests the relevance of detecting RAF fusion in a selected population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study compares cycling and walking efficiency, and energy expenditure in children with bilateral spastic cerebral palsy (CP). In children with CP, locomotion with body weight support aids such as a tricycle is a potential alternative for less exhausting movements., Methods: Nine children with CP traveled at comfortable speed for 6 minutes by cycling and walking. The energy expenditure index (EEI) and the percentage of the reserve heart rate (%HRR) were calculated., Results: The EEI was lower while cycling than walking, the traveled distance was higher while cycling than walking, and %HRR remained similar between cycling and walking., Conclusion: Cycling appears an efficient alternative to walking for children with CP for adapted school environments and in the community., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest., (Copyright © 2024 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)