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Background: Our aim was to assess the feasibility, acceptability, and efficacy of a 12-week in-person Creative Arts Therapy intervention in reducing psychological distress and burnout symptoms in nonpatient-facing healthcare workers. Burnout and psychological distress among nonpatient-facing healthcare workers are significant and understudied problems in healthcare systems., Methods: Nonpatient-facing healthcare workers with burnout symptoms were randomly assigned to one of 4 Creative Arts Therapy modalities (art, music, creative writing, or dance/movement) or a control group. The intervention consisted of 12 weekly 90-minute sessions. All participants completed baseline and follow-up assessments postintervention and at 4-, 8-, and 12-months. Primary outcomes were feasibility (session attendance) and acceptability (Client Satisfaction Questionnaire, CSQ-8). Secondary outcomes included changes in psychological distress; symptoms of burnout, anxiety, and depression; and turnover intention., Results: Of 168 active participants, 164 (98%) completed postintervention surveys, with 90% follow-up at 12 months. Participants attended a mean of 10.7 sessions (SD = 3.2). The median CSQ-8 score for the program was 31 (17-32). Intervention group participants demonstrated significant improvements in symptoms of anxiety (-40.6%), depression (-29.0%), emotional exhaustion (-15.0%), and depersonalization (-14.3%), and reduced turnover intention (-6.1%) compared to the control group. At 12-months, improvements in depressive and anxiety symptoms persisted., Conclusions: The Creative Arts Therapy intervention was feasible, acceptable, and effective in reducing psychological distress and burnout symptoms among nonpatient-facing healthcare workers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: It has been hypothesized that both atrial fibrillation (AF) and medications for AF are poorly tolerated in athletes., Objective: The purpose of this study was to determine the impact of AF and AF treatments on sports performance., Methods: An Internet-based survey, initiated via StopAfib.org, queried the impact of AF and treatment modalities on sports performance, training, and symptoms. Performance (rated in comparison to personal best), frequency of training, and competition were compared before onset of AF symptoms vs when symptoms at worst, via paired Wilcoxon, and then similarly compared in relation to participants' AF treatments., Results: Between May 13, 2019, and February 29, 2020, 1055 athletes responded (78% male, median age 61-70 years). The sports most reported were cycling (25%) and running (20%). Development of AF was associated with declining sports performance, competition, and training frequency. Of 565 participants who detrained, 31% reported no change in symptoms, 56% reported decreased frequency, and 13% reported no further AF. Among athletes who received treatment, ablation was associated with greater improvement in sports performance than use of medications. Of 262 athletes currently taking medication, 27% reported that it was completely effective, 58% partially effective, and 15% not effective. Of 653 athletes who have taken medication currently and/or in the past, 43% reported side effects, most commonly fatigue, low energy, or decreased athletic performance., Conclusion: Athletes reported that AF was associated with worsening sports performance. Among AF treatment modalities, ablation was associated with the greater reported improvement in sports performance than use of medications, which also had a high frequency of side effects., Competing Interests: Disclosures Dr Lampert reports being on the advisory board and receiving honoraria from Medtronic; and research funding from Medtronic, Abbott, and Boston Scientific (all ended as of May 2022). Dr Lee reports being on the advisory board of Medtronic. All other authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The duration of mechanical thrombectomy (MT) is a negative predictor of outcomes in acute ischemic stroke (AIS), yet the precise mechanisms are unclear. We investigated whether the placement of large-bore catheters intracranially reduces blood flow to the ischemic penumbra and diminishes the efficacy of MT., Methods: We investigated the impact of different catheter sizes on flow through the intracranial circulation using an in vitro model. Data from a multicenter international registry of AIS patients undergoing MT between January 2016 and December 2023 were reviewed. Intracranial procedure time (icPT) from catheter placement to thrombectomy completion was analyzed using propensity score (PS) matched analysis of patients with successful recanalization achieved in <30 min versus ≥30 min (n=1006/group). Primary outcome was modified Rankin Scale (mRS) score at 90 days (mRS 0-2 favorable). Secondary outcomes included mortality, symptomatic intracranial hemorrhage (sICH), and need for craniectomy., Results: Using our flow model, we demonstrated a significant reduction in middle cerebral artery and anterior cerebral artery blood flow with the use of larger caliber catheters in the internal carotid artery. Controlling for covariates in 3318 patients, longer icPT predicted lower odds of 90-day favorable outcome (adjusted odds ratio (aOR) 0.87, P<0.01), increased mortality (aOR 1.03, P<0.01), higher decompressive craniectomy rates (aOR 1.07, P<0.01), and increased sICH (aOR 1.07, P<0.01). Each additional 10 mins of icPT correlated with a 13% decrease in recanalization success. The impact of icPT on outcomes was consistent regardless of recanalization success, though catheter size influenced effects. Reduced intraprocedural blood pressure worsened icPT's effects., Conclusions: This study is the first to demonstrate the risks associated with the duration of catheter use during MT and to propose strategies to mitigate these risks in AIS., Competing Interests: Competing interests: Sami Al Kasab: Grant from Stryker for RESCUE-ICAS registry. Adam Arthur: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Perfuze, Scientia, Siemens, Stryker. Research support from Balt, Medtronic, Microvention, Penumbra, Siemens. Shareholder in several companies. Shinichi Yoshimura: Lecture fee from Stryker, Medtronic, Johnson & Johnson, Kaneka Medics. Min Park: Consultant for Medtronic. Waleed Brinjikji: Equity, royalties, consulting fees, and leadership roles in several companies including Medtronic, Stryker, and others. Charles Matouk: Consultant for Stryker, Medtronic, Microvention, Penumbra, and Silk Road Medical. Speaker for Penumbra and Silk Road Medical. Daniele Romano: Consultant for Penumbra, Balt, Microvention, Phenox. David J Altschul: Consultant for MicroVention, Stryker, and Cerenovus. Richard Williamson: Consultant for Medtronic, Stryker, and Synaptive Medical. Reade De Leacy: Research grants, consultant roles, and minor equity interest in several companies. Mohamad Ezzeldin: Speaker for Viz.ai and stocks in Galaxy Therapeutics. Peter Kan: Grants, consulting roles, stock ownership in several companies. Michael Levitt: Grants, consulting agreements, equity interests in several companies. Jonathan A Grossberg: Grant support and consulting roles in several entities. Alejandro M Spiotta: Research support from Penumbra, Microvention, Medtronic, Stryker, RapidAI, Brain Aneurysm Foundation. Consultant for Penumbra, Terumo, and RapidAI. Other authors: No conflict of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: We aimed to develop and validate a prediction score for futile recanalization (FR) for large vessel occlusion (LVO) presenting low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for patients who underwent endovascular thrombectomy (EVT)., Methods: Patients with anterior circulation LVO with low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score ≥2b) from Stroke Thrombectomy and Aneurysm Registry were retrospectively analyzed. FR was defined as 90-day modified Rankin Scale (mRS) scores ≥4 despite successful EVT. Multivariable logistic regression was used to identify independent predictors of FR, and they were used to create a clinical score. The performance of the score was assessed by receiver operating characteristic curve analyses., Results: Of 219 patients, 170 and 49 patients were randomly assigned to the training and validation cohort, respectively. Independent predictors of FR identified in the training cohort were used to construct the SNAP score: site of occlusion (middle cerebral artery = 0, internal carotid artery = 1), National Institutes of Health Stroke Scale score at admission (≤10 = 0, 10 to 19 = 1, ≥20 = 2), age (<75 = 0, ≥75 = 2), and prestroke mRS score (0-3). Receiver operating characteristic curve analyses of the SNAP score in the training and validation cohorts showed areas under the curve of 0.79 (95% CI 0.72-0.86) and 0.79 (95% CI 0.65-0.92) for predicting FR, respectively. A SNAP score ≥5 had a positive predictive value of 92.1% [95% CI 78.8%-97.3%] for FR., Conclusion: The SNAP score may be useful in predicting FR after EVT in low-ASPECTS patients with LVO. It can provide patients, family members, and physicians with reliable outcome expectations among patients with acute ischemic stroke with large infarcts., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: The impact of race on outcomes in the treatment of intracranial aneurysm (IA) remains unclear. We aimed to investigate the relationship between race classified into White, Black, Hispanic, and other and treatment outcomes in patients with ruptured and unruptured IAs., Methods: The study population consisted of 2836 patients with IA with endovascular treatment or microsurgical treatment (MST) from 16 centers in the United States and Asia, all participating in the observational "STAR" registry. The primary outcome was a 90-day modified Rankin Scale of 0 to 2. Secondary outcomes included periprocedural cerebral infarction and intracranial hemorrhage, perioperative symptomatic cerebral vasospasm in ruptured IA and mortality, and all causes of mortality within 90 days., Results: One thousand fifty-three patients were White (37.1%), 350 were Black (12.3%), 264 were Hispanic (9.3%), and 1169 were other (41.2%). Compared with White patients, Hispanic patients had a significantly lower proportion of primary outcome (adjusted odds ratio [aOR] 0.36, 95% CI, 0.23-0.56) and higher proportion of the periprocedural cerebral infarction, perioperative mortality, and all causes of mortality (aOR 2.53, 95% CI, 1.40-4.58, aOR 1.84, 95% CI, 1.00-3.38, aOR 1.83, 95% CI, 1.06-3.17, respectively). Outcomes were not significantly different in Black and other patients. The subgroup analysis showed that Hispanic patients with age ≥65 years (aOR 0.19, 95% CI, 0.10-0.38, interaction P = .048), Hunt-Hess grades 0 to 3 (aOR 0.29, 95% CI, 0.19-0.46, interaction P = .03), and MST (aOR 0.24, 95% CI, 0.13-0.44, interaction P = .04) had a significantly low proportion of primary outcome., Conclusion: This study demonstrates that Hispanic patients with IA are more likely to have a poor outcome at 90 days after endovascular treatment or MST than White patients. Physicians have to pay attention to the selection of treatment modalities, especially for Hispanic patients with specific factors to reduce racial discrepancies., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset., Methods: A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal., Results: Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04)., Conclusion: Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

The current study assessed the effectiveness of delivering safer gambling messaging to regular sport bettors on social media. It also assessed whether the content of the message impacted message effectiveness. A 3 × 2 mixed factorial design was employed, with 281 participants randomly assigned to follow one of three Twitter accounts. The accounts either sent out informational messages, self-appraisal messages or emotional self-efficacy messages. Participants reported betting behaviour from the two weeks prior to following the accounts, in addition to during the two-week intervention period, using information from their online gambling accounts. Participants reported readiness to change gambling behaviour pre and post the two-week intervention period. A significant main effect of intervention stage highlighted reductions in betting behaviour and increased readiness to change behaviour. However, there was no significant main effect of condition and no significant interaction between intervention stage and condition upon betting behaviour or readiness to change. The findings suggest receiving safer gambling messages on social media may lead to a reduction in betting behaviour. However, similar reductions in behaviour were observed in the experimental and control conditions. Further research is needed to clarify whether changes in behaviour observed in the current study would extend over a longer period of time., (© 2024. The Author(s).)

Background: The definitive impact of onset to arterial puncture time (OPT) on 90-day mortality after endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) caused by anterior circulation large vessel occlusion (LVO) remains unknown. The present study aimed to evaluate the influence of OPT on 90-day mortality in anterior circulation AIS-LVO patients who underwent EVT., Methods: Data from 33 international centers were retrospectively analyzed. The receiver operating characteristic curve analysis was used to identify a cutoff for OPT. A propensity score-matched analysis was performed. The primary outcome was 90-day mortality (modified Rankin Scale [mRS] 6). Secondary outcomes included mortality at discharge, 90-day good outcome (mRS 0-2), 90-day poor outcome (mRS 5-6), successful recanalization (defined as postprocedure modified Thrombolysis in Cerebral Infarction scale ≥2b), and intracranial hemorrhage., Results: A total of 2842 AIS-LVO patients with EVT were included. The cutoff for OPT for 90-day mortality was 180 min. Of these 378 patients had OPT <180 min and 378 patients had OPT ≥180 min in the propensity score-matched cohort (n = 756). Patients with OPT <180 min were less likely to have 90-day mortality (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.51-0.96) and poor outcome (OR 0.71, 95% CI 0.53-0.96), and more likely to have 90-day good outcome (OR 1.55, 95% CI 1.16-2.08). Other outcomes showed no significant differences., Conclusions: This study showed that OPT <180 min was less related to 90-day mortality and poor outcome, and more to 90-day good outcome in AIS-LVO patients who underwent EVT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Robotic surgery for localized prostate cancer offers a greater range of motion attributed to the EndoWrist instruments. Postoperative outcomes are linked to the quality of vesico-urethral anastomosis. Trainees frequently complain of suturing difficulty in a back-handed fashion. We aimed to analyze wrist motion using the DaVinci simulator. We hypothesized that using the thumb and index finger would allow superior surgical proficiency when compared to the middle finger., Methods: After institutional review board approval, we recruited 42 medical students in one academic medical center. Students were randomly assigned to start with their thumb and index finger (1&2) or thumb and middle finger (1&3). Three standardized modules were used with nine metrics calculated, including: score, total time, economy of motion, efficiency score, collisions, inaccurate puncture, wound approximation, out of view, and penalty subtotal. Statistical analysis of the metrics was calculated using SPSS., Results: Three metrics were found to have differences between the finger placement of 1&3 compared to 1&2. The number of collisions, wound approximation, and penalty score where 1&3 were used had a lower score in each. The number of collisions was 5.7 less in the 1&3 finger placement (p=0.046). This metric was found to have statistically significant differences between finger placement where 1&3 had a lower score compared to 1&2. The wound approximation score was 0.2 points lower when using the 1&3 placement (p=0.075). Lastly, the penalty assigned was 6.5 points lower when using 1&3 (p=0.069)., Conclusions: Although finger placement did not affect the overall score of the completed simulation, instrument collisions and unnecessary wound complications may lead to adverse outcomes when using 1&2 despite offering a wider range of motion. This may be due to decreased comfort in hand position. Trainees may be able to improve the effectiveness of their vesico-urethral anastomosis during robotic-assisted radical prostatectomy.

Although dynamic alterations in transcriptional, translational, and metabolic programs have been described in T cells, the factors and pathways guiding these molecular shifts are poorly understood, with recent studies revealing a disassociation between transcriptional responses and protein expression following T cell receptor (TCR) stimulation. Previous studies identified interferon regulatory factor 5 (IRF5) in the transcriptional regulation of cytokines, chemotactic molecules and T effector transcription factors following TCR signaling. In this study, we identified T cell intrinsic IRF5 regulation of mTORC1 activity as a key modulator of CD40L protein expression. We further demonstrated a global shift in T cell metabolism, with alterations in glutamine metabolism accompanied by shifts in T cell populations at the single cell level due to loss of Irf5 . T cell conditional Irf5 knockout mice in a murine model of experimental autoimmune encephalomyelitis (EAE) demonstrated protection from clinical disease with conserved defects in mTORC1 activity and glutamine regulation. Together, these findings expand our mechanistic understanding of IRF5 as an intrinsic regulator of T effector function(s) and support the therapeutic targeting of IRF5 in multiple sclerosis., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Background: A combination of intravenous (IVT) or intra-arterial (IAT) thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been investigated. However, there is limited data on patients who receive both IVT and IAT compared with IVT alone before MT., Methods: STAR data from 2013 to 2023 was utilized. We performed propensity score matching between the two groups. The primary outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day modified Rankin Scale (mRS) score 0-2. Secondary outcomes included successful recanalization (modified treatment in cerebral infarction (mTICI) ≥2B, ≥2C), early neurological improvement, any intracranial hemorrhage (ICH), and 90-day mortality., Results: A total of 2454 AIS-LVO patients were included. Propensity matching yielded 190 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio (OR): 0.80, 95% confidence interval (CI) 0.51-1.24, P=0.37; OR: 0.60, 95% CI 0.29 to 1.24, P=0.21, respectively). Rates of successful recanalization and early neurological improvement (ENI) were significantly lower in MT+IVT + IAT. mRS 0-1 and mortality were not significantly different between the two groups. However, the MT+IVT + IAT group demonstrated superior rates of good functional outcomes (90-day mRS 0-1) compared with patients in the MT+IVT group who had mTICI ≤2B, (OR: 2.18, 95% CI 1.05 to 3.99, P=0.04)., Conclusion: The combined use of IAT and IVT thrombolysis in AIS-LVO patients undergoing MT is safe. Although the MT+IVT+ IAT group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes were favorable in this group suggesting a potential delayed benefit of IAT., Competing Interests: Competing interests: HM received a lecture fee from Daiichi-Sankyo and Stryker and consulting services fees from B Braun. ILM: speakers' honoraria from Pfizer and Bristol-Myers Squibb. RMS: research is supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, Department of Health Biomedical Research Grant (21K02AWD-007000) and by National Institute of Health (R01NS111119-01A1) and (UL1TR002736, KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. RMS has an unrestricted research grant from Medtronic and Balt and has consulting and teaching agreements with Penumbra, Abbott, Medtronic, Balt, InNeuroCo, Cerenovus, Naglreiter, Tonbridge, Von Medical, and Optimize Vascular. MNP: Grants from the Swiss National Science Foundation (SNF) for the DISTAL trial (33IC30198783) and TECNO trial (32003B204977), Grant from Bangerter-Rhyner Stiftung for the DISTAL trial. Unrestricted Grants for the DISTAL trial from Stryker Neurovascular Inc., Phenox GmbH, Penumbra Inc., and Rapid Medical Inc., Sponsor-PI SPINNERS trial (Funded by a Siemens Healthineers AG Grant), Research agreement with Siemens Healthineers AG, Local PI for the ASSIST, EXCELLENT, TENSION, COATING, SURF, and ESCAPE-NEXT trials. Speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Siemens Healthineers AG. ES: consults for Medtronic, Microvention, Rapid Medical. SY: received lecture fees from Stryker, Medtronic, Johnson & Johnson, Kaneka Medics. HC: Consultant for Medtronic and Microvention. JAG: Georgia Research Alliance, Emory Medical Care Foundation, Neurosurgery Catalyst, Consultant: Cognition, Imperative Care. DGR: Consultant for Penumbra, Balt, Microvention, Phenox. OT: Consulting Agreements: Viz.AI, Inc., Penumbra, Inc, Balt, Inc, Stryker Inc, Imperative Inc. Proctor: Microvention Inc, Medtronic Inc. Educational/Research Grants: Q’apel Inc, Steinberg Foundation. CM: Consultant for Stryker, Medtronic, Microvention, Penumbra, and Silk Road Medical. Speaker for Penumbra and Silk Road Medical. Contact PI for NIH Grant R21NS128641. MSP: Consultant for Medtronic. MRL: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Medtronic, Aeaean Advisers and Metis Innovative; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. WB: Holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN. RW: Consultant for Medtronic, Stryker, and Synaptive Medical. PN: Consultant for Penumbra, Medtronic, Stryker, Cerenovus, and Balt. PK: Grants from the NIH (1U18EB029353-01) and unrestricted educational grants from Medtronic and Siemens. Consultant for Imperative Care and Stryker Neurovascular. Stock ownership in Vena Medical. RDL: PI for Imperative Trial; Research grants from Siemens Healthineers and Kaneka medical. Consultant for Cerenovus, Stryker Neurovascular and Sim & Cure. Minor equity interest Vastrax, Borvo medical, Synchron, Endostream, Von Vascular, Radical catheters, and Precision Recovery Inc. SAC: Consultant and proctor for Medtronic and Microvention. ME: Consultant for Viz.ai and Imperative care. Investments in Galaxy Therapeutics. DJA: Consultant for MicroVention, Stryker, and Cerenovus. RG: Consultant for Balt Neurovascular, Cerenovus, Medtronic Neurovascular, Rapid Medical, and Stryker Neurovascular. AMS: Consultant for Penumbra, Terumo, RapidAI, Cerenovus. AA: Consultant for Cerenovus. SSE, RAK, BM, CMC, MMS, AO, NLN, JI, PJ, JTK, SQW, AR, AA, JM, IF, AP, FS, JO, RC, MM, ED, NG: none., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whereas mechanical thrombectomy (MT) has become standard-of-care treatment for patients with salvageable brain tissue after acute stroke caused by large-vessel occlusions, the results of MT in patients with medium-vessel occlusions (MEVOs), particularly in the posterior cerebral artery (PCA), are not well known., Methods: Using data from the international Stroke Thrombectomy and Aneurysm Registry (STAR), we assessed presenting characteristics and clinical outcomes for patients who underwent MT for primary occlusions in the P2 PCA segment. As a subanalysis, we compared the PCA MeVO outcomes with STAR's anterior circulation MeVO outcomes, namely middle cerebral artery (MCA) M2 and M3 segments., Results: Of the 9812 patients in STAR, 43 underwent MT for isolated PCA MeVOs. The patients' median age was 69 years (interquartile range 61-79), and 48.8% were female. The median NIH Stroke Scale score was 9 (range 6-17). After recanalization, 67.4% of patients achieved successful recanalization (modified treatment in cerebral infarction score [mTICI] ≥ 2b), with a first-pass success rate of 44.2%, and 39.6% achieved a modified Rankin score of 0-2 at 90 days. Nine patients (20.9%) had died by the 90-day follow-up. In comparison with M2 and M3 MeVOs, there were no differences in presenting characteristics among the three groups. Patients with PCA MeVOs were less likely to undergo intra-arterial thrombolysis (4.7% PCA vs. 10.1% M2 vs. 16.2% M3, p = 0.046) or to achieve successful recanalization (mTICI ≥ 2b, 67.4%, 86.7%, 82.3%, respectively, p < 0.001); however, there were no differences in the rates of successful first-pass recanalization (44.2%, 49.8%, 52.3%, respectively, p = 0.65)., Conclusions: We describe the STAR experience performing MT in patients with PCA MeVOs. Our analysis supports that successful first-pass recanalization can be achieved in PCA MEVOs at a rate similar to that in MCA MeVOs, although further study and possible innovation may be necessary to improve successful PCA MeVO recanalization rates., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. IM: payment or honoraria from Pfizer and Bristol-Myers Squibb. RMS: grants from or contracts with NREF, Joe Niekro Foundation, Brain Aneursym Foundation, Bee Foundation, Department of Health Biomedical Research Grant, National Institutes of Health, Medtronic, and Balt; consulting for Penumbra, Abbott, Medtronic, Balt, InNeuroCo, Cerenovus, Naglreiter, Tonbridge, and Von Medical Optimize Vascular. MNP: grants from or contracts with Swiss National Science Foundation, Bangerter-Rhyner Stiftung, and Stryker. SY: payment or honoraria from Stryker, Medtronic, Johnson & Johnson, and Kaneka Medics for lectures. HC: consulting for Medtronic and Microvention. AAlaraj: consulting for Cerenovus. ME: grants from or contracts with Siemens Healthineers and Kaneka Medical; consulting for Viz.ai and Imperative Care; and stock in Galaxy Therapeutics. DGR: consulting for Penumbra, Balt, Microvention, and Phenox. OT: grants from QApel Inc and Steinberg Foundation; consulting for Viz.ai, Penumbra, Balt, Stryker, and Imperative; and payment or honoraria from Microvention and Medtronic. CM: NIH Grant; consulting for Stryker, Medtronic, Microvention, Penumbra, and Silk Road Medical; and payment or honoraria from Penumbra and Silk Road Medical. MSP: consulting for Medtronic. MRL: grants from Medtronic and Siemens; consulting for Medtronic, Aeaean Advisers, and Metis Innovative; board participation at Arsenal Medical; editorial board participation at Journal of NeuroInterventional Surgery; and stock in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, and Hyperion Surgical. WB: royalties or licenses from Medtronic and Balloon Guide Catheter Technology; consulting for Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt; leadership role in MIVI Neurovascular, Marblehead Medical LLC, Inventional Neuroradiology journal, Piraeus Medical, and WFITN; and stock in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. RW: consulting for Medtronic, Stryker, and Synaptive Medical;PN: consulting for Penumbra, Medtronic, Stryker, Cerenovus, and Balt. PK: grants from NIH, Medtronic, and Siemens; consulting for Imperative Care and Stryker Neurovascular; and stock in Vena Medical. RDL: grants or contracts from Siemens Healthineers and Kaneka Medical; consulting for Cerenovus, Stryker Neurovascular, and Sim & Cure; stock in Vastrax, Borvo Medical, Synchron, Endostream, Von Vascular, Radical Catheters, Precision Recovery Inc; and other interests in PI for Imperative Trial. SC: consulting for Medtronic and Microvention. DJA: grant or contract with The Bee Foundation; consulting for MicroVention, Stryker, QApel, Synchron, and Cerenovus; and stock in Von Vascular. ASpiotta: consulting for Penumbra, Terumo, RapidAI, and Cerenovus. RG: consulting for Balt Neurovascular, Cerenovus, Medtronic Neurovascular, Rapid Medical, and Stryker Neurovascular.

Background: Ethylene glycol poisoning causes metabolic acidosis, organ injury, and death. Ethylene glycol testing is unavailable in many areas. Our laboratory uses an automated glycerol dehydrogenase enzymatic assay to screen for ethylene glycol. We sought to determine how often ethylene glycol results were available within 12 h of the first dose of fomepizole., Methods: Records from a single poison center were reviewed from December 2016 to December 2019. Cases were identified by searching for cases that received fomepizole. Outcomes included whether results were available within 12 h, and the turnaround time from time of laboratory order to result., Results: Of the 125 cases of suspected toxic alcohol poisoning identified, 73 had screening for ethylene glycol by enzymatic assay. Results were available within 12 h of the initial fomepizole dose in 58 (79%) cases with a median turnaround time of 391 min., Discussion: We have demonstrated clinically acceptable turnaround times using an automated screening ethylene glycol assay. The major limitations include lack of approval for this test at this time, the use of voluntarily reported poison center data, and lack of assessment of patient outcomes., Conclusion: Enzymatic screening for ethylene glycol yielded results within 12 h in 79% of cases.

School-based oral health programs are an effective approach to population-based care and a stalwart of public health, especially in rural and underserved communities. Lessons learned during the COVID-19 pandemic have informed contemporary strategies and policies to ensure integration into the delicate dental safety net in the Carolinas., Competing Interests: Acknowledgments: The team wishes to acknowledge one of the original thought leaders and influencers of our program design, Dr. Mark Doherty. We thank him posthumously for his visionary commitment to the design of the initiative. Funding: Funding for the SBOHP was made possible by The Duke Endowment (a major funder of the North Carolina Medical Journal) and the Blue Cross Blue Shield Foundations of both North and South Carolina., (Copyright ©2024 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact on the P2X7 receptor. There was a significant reduction in monocyte count in vivo at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ 'non-classical' monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. In vitro, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis., Competing Interests: Declaration of competing interest, (Copyright © 2024. Published by Elsevier Inc.)

Importance: Although psychological distress is common among survivors of critical illness, there are few tailored therapies., Objective: To determine the optimal method for delivering a mindfulness intervention via a mobile app for critical illness survivors., Design, Setting, and Participants: This randomized clinical trial used a 2 × 2 × 2 factorial design and was conducted at 3 sites among survivors of critical illness with elevated postdischarge symptoms of depression. The study was conducted between August 2019 and July 2023., Interventions: Participants were randomized to 1 of 8 different groups as determined by 3 two-level intervention component combinations: intervention introduction method (mobile app vs therapist call), mindfulness meditation dose (once daily vs twice daily), and management of increasing symptoms (mobile app vs therapist call)., Main Outcomes and Measures: The primary outcome was the 9-item Patient Health Questionnaire (PHQ-9) depression scale score (range, 0-27) at 1 month. Secondary outcomes included anxiety (7-item Generalized Anxiety Disorder) and posttraumatic stress disorder (Posttraumatic Stress Scale) symptoms at 1 and 3 months, adherence, and feasibility. General linear models were used to compare main effects and interactions of the components among intervention groups. A formal decisional framework was used to determine an optimized intervention version., Results: A total of 247 participants (mean [SD] age, 50.2 [15.4] years; 104 [42.1%] women) were randomized. Twice-daily meditation compared with once-daily meditation was associated with a 1.2 (95% CI, 0.04-2.4)-unit lower mean estimated PHQ-9 score at 1 month and a 1.5 (95% CI, 0.1-2.8)-unit lower estimated mean score at 3 months. The other 2 intervention components had no main effects on the PHQ-9. Across-group adherence was high (217 participants [87.9%] using the intervention at trial conclusion) and retention was strong (191 [77.3%] and 182 [73.7%] at 1 and 3 months, respectively)., Conclusions and Relevance: A mindfulness intervention for survivors of critical illness that included an app-based introduction, twice-daily guided meditation, and app-based management of increasing depression symptoms was optimal considering effects on psychological distress symptoms, adherence, and feasibility., Trial Registration: ClinicalTrials.gov Identifier: NCT04038567.

Objectives: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death., Design: A retrospective multicenter cohort study., Setting: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States., Patients: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF., Interventions: None., Measurements and Main Results: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40)., Conclusions: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice., Competing Interests: This article was supported by an Institutional National Research Service Award (T32) funded by the National Institute of Health, National Heart, Lung, and Blood Institute (T32 HL007085). Dr. Ho disclosed government work. Dr. Sottile’s institution received funding from the National Heart, Lung, and Blood Institute; he received support for article research from the National Institutes of Health. 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.)

Refined management of mechanically ventilation is an obvious target for improving patient outcomes, but is impeded by the nature of data for study and hypothesis generation. The connections between clinical outcomes and temporal development of iatrogenic injuries current lung-protective ventilator settings remain poorly understood. Analysis of lung-ventilator system (LVS) evolution at relevant timescales is frustrated by data volume and multiple sources of heterogeneity. This work motivates, presents, and validates a computational pipeline for resolving LVS systems into the joint evolution of data-conditioned model parameters and ventilator information. Applied to individuals, the workflow yields a concise low-dimensional representation of LVS behavior expressed in phenotypic breath waveforms suitable for analysis. The effectiveness of this approach is demonstrated through application to multi-day observational series of 35 patients. Individual patient analyses reveal multiple types of patient-oriented dynamics and breath behavior to expose the complexity of LVS evolution; less than 10% of phenotype changes related to ventilator settings changes. Dynamics are shown to including both stable and unstable phenotype transitions as well as both discrete and continuous changes unrelated to ventilator settings. At a cohort scale, 721 phenotypes constructed from individual data are condensed into a set of 16 groups that empirically organize around certain settings (positive end-expository pressure and ventilator mode) and structurally similar pressure-volume loop characterizations. Individual and cohort scale phenotypes, which may be refined by hypothesis-specific constructions, provide a common framework for ongoing temporal analysis and investigation of LVS dynamics., Competing Interests: Declarations of Interest None. The authors have no conflicts of interest to disclose.

Background: Psychological distress symptoms are present and persistent among many patients who survive a critical illness like COVID-19., Research Question: Could a self-directed mobile app-delivered mindfulness intervention be feasibly and rapidly implemented within a clinical trials network to reduce distress symptoms?, Study Design and Methods: A randomized clinical trial was conducted between January 2021 and May 2022 at 29 US sites and included survivors of hospitalization due to COVID-19-related illness with elevated symptoms of depression at discharge. Participants were randomized to intervention or usual care control. The intervention consisted of four themed weeks of daily audio, video, and text content. All study procedures were virtual. The primary outcome was depression symptoms assessed with the Patient Health Questionnaire 9 at 3 months. Secondary outcomes included anxiety (Generalized Anxiety Disorder 7-item scale), quality of life (EQ-5D), and adherence. We used general linear models to estimate treatment arm differences in outcomes over time., Results: Among 56 randomized participants (mean age ± SD, 51.0 ± 13.2 years; 38 female [67.9%]; 14 Black participants [25%]), 45 (intervention: n = 23 [79%]; control: n = 22 [81%]) were retained at 6 months. There was no difference in mean improvement between intervention and control participants at 3 months in Patient Health Questionnaire 9 (-0.5 vs 0.1), Generalized Anxiety Disorder 7-item scale (-0.3 vs 0.1), or EQ-5D (-0.03 vs 0.02) scores, respectively; 6-month results were similar. Only 15 participants (51.7%) initiated the intervention, whereas the mean number ± SD of the 56 prescribed intervention activities completed was 12.0 ± 15.2. Regulatory approvals delayed trial initiation by nearly a year., Interpretation: Among survivors of COVID-19 hospitalization with elevated psychological distress symptoms, a self-directed mobile app-based mindfulness intervention had poor adherence. Future psychological distress interventions mobilized at broad scale should focus efforts on patient engagement and regulatory simplification to enhance success., Trial Registration: ClinicalTrials.gov; No.: NCT04581200; URL: www.clinicaltrials.gov., Competing Interests: Financial/Nonfinancial Disclosures None declared.

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproved. The NHLBI of the NIH assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and well-being of ARDS survivors.

Background: Cognitive load theory asserts that learning and performance degrade when cognitive load exceeds working memory capacity. This is particularly relevant in the learning environment of ICU rounds, when multidisciplinary providers integrate complex decision-making and teaching in a noisy, high-stress environment prone to cognitive distractions., Research Question: What features of ICU rounds correlate with high provider cognitive load?, Study Design and Methods: This was an observational, multisite study of multidisciplinary providers during ICU rounds. Investigators recorded rounding characteristics and hourly extraneous cognitive load events during rounds (defined as distractions, episodes of split-attention or repetition, and deviations from standard communication format). After rounds, investigators measured each provider's cognitive load using the provider task load (PTL), an instrument derived from the National Aeronautics and Space Administration Task Load Index survey that assesses perceived workload associated with complex tasks. Relationships between rounding characteristics, extraneous load, and PTL score were evaluated using mixed-effects modeling., Results: A total of 76 providers were observed during 32 rounds from December 2020 to May 2021. The mean rounding census ± SD was 12.5 ± 2.9 patients. The mean rounding time ± SD was 2 h 17 min ± 49 min. The mean extraneous load ± SD was 20.5 ± 4.5 events per hour, or one event every 2 min 51 s. This included 8.6 ± 3.4 distractions, 8.2 ± 4.2 communication deviations, 1.9 ± 1.4 repetitions, and 1.8 ± 1.3 episodes of split-attention per hour. Controlling for covariates, the hourly extraneous load events, number of new patients, and number of higher acuity patients were each associated with increased PTL score (slope, 2.40; 95% CI, 0.76-4.04; slope, 5.23; 95% CI, 2.02-8.43; slope, 3.35; 95% CI, 1.34-5.35, respectively)., Interpretation: Increased extraneous load, new patients, and patient acuity were associated with higher cognitive load during ICU rounds. These results can help direct how the ICU rounding structure may be modified to reduce workload and optimize provider learning and performance., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Ventilator dyssynchrony may be associated with increased delivered tidal volumes (V t s) and dynamic transpulmonary pressure (ΔP L,dyn ), surrogate markers of lung stress and strain, despite low V t ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential., Design: A prospective cohort analysis to delineate the association between ten types of breaths and delivered V t , ΔP L,dyn , and transpulmonary mechanical energy., Setting: Patients admitted to the medical ICU., Patients: Over 580,000 breaths from 35 patients with acute respiratory distress syndrome (ARDS) or ARDS risk factors., Interventions: None., Measurements and Main Results: Patients received continuous esophageal manometry. Ventilator dyssynchrony was identified using a machine learning algorithm. Mixed-effect models predicted V t , ΔP L,dyn , and transpulmonary mechanical energy for each type of ventilator dyssynchrony while controlling for repeated measures. Finally, we described how V t , positive end-expiratory pressure (PEEP), and sedation (Richmond Agitation-Sedation Scale) strategies modify ventilator dyssynchrony's association with these surrogate markers of lung stress and strain. Double-triggered breaths were associated with the most significant increase in V t , ΔP L,dyn , and transpulmonary mechanical energy. However, flow-limited, early reverse-triggered, and early ventilator-terminated breaths were also associated with significant increases in V t , ΔP L,dyn , and energy. The potential of a ventilator dyssynchrony type to increase V t , ΔP L,dyn , or energy clustered similarly. Increasing set V t may be associated with a disproportionate increase in high-volume and high-energy ventilation from double-triggered breaths, but PEEP and sedation do not clinically modify the interaction between ventilator dyssynchrony and surrogate markers of lung stress and strain., Conclusions: Double-triggered, flow-limited, early reverse-triggered, and early ventilator-terminated breaths are associated with increases in V t , ΔP L,dyn , and energy. As flow-limited breaths are more than twice as common as double-triggered breaths, further work is needed to determine the interaction of ventilator dyssynchrony frequency to cause clinically meaningful changes in patient outcomes., Competing Interests: Dr. Sottile’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) (HL145011). Drs. Sottile, Smith, and Albers received support for article research from the National Institutes of Health. Dr. Smith’s institution received funding from the NHLBI. 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.)

Background and Objectives: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT)., Methods: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation., Results: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable., Conclusion: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: Some studies have shown that female patients had a poorer prognosis after endovascular treatment for ruptured intracranial aneurysm than male patients. However, data have been sparse regarding differences in the periprocedural and perioperative complication rate with ruptured and unruptured intracranial aneurysms., Methods: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry, a database of 9 institutions in the United States, Europe, and Asia. The study presented intracranial aneurysms after microsurgical and/or endovascular treatment from January 1, 2013, to December 31, 2022. The primary outcome was incidence of periprocedural cerebral infarction. Secondary outcomes were periprocedural intracranial hemorrhage, periprocedural mortality, perioperative vasospasm, and functional outcome at 90 days after procedure., Results: Among 3342 patients with aneurysm, 2447 were female and 857 were male, and the mean age of female and male patients was 59.6 and 57.1 years, respectively. Current smoker, family history of aneurysm, and ruptured aneurysm were observed in 23.5% vs 35.7 %, 10.8 % vs 5.7%, and 28.2% vs 40.5% of female and male patients, respectively. In female patients, internal carotid artery aneurysms were more commonly observed (31.1% vs 17.3%); however, anterior cerebral artery aneurysms were less commonly observed (18.5% vs 33.8%) compared with male patients. Periprocedural cerebral infarction rate was lower in female than male patients (2.4% vs 4.4%; P = .002). The adjusted odds ratio of primary outcome of female to male patients was 0.72 (95% CI, 0.46-1.12). Incidence of periprocedural intracranial hemorrhage and periprocedural mortality and perioperative symptomatic vasospasm and functional outcome was similar in both groups. In subgroup analysis, periprocedural cerebral infarction due to microsurgical treatment occurred frequently in male patients while incidence in endovascular treatment was similar in both groups (interaction P = .005)., Conclusion: This large multicenter registry of patients undergoing intracranial aneurysm treatment found that female patients were not at increased risk of perioperative complications., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Purpose: Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2-5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT., Methods: This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT for internal carotid artery or middle cerebral artery (M1) stroke., Results: Of the 10,229 patients who underwent MT, 234 met the inclusion criteria. Of those, 98 (41.9%) achieved mTICI 2b, and 136 (58.1%) achieved mTICI 2c/3. There were no significant differences in baseline characteristics between the two groups. The 90-day favorable outcome (modified Rankin Scale score: 0-3) was significantly better in the mTICI 2c/3 group than in the mTICI 2b group (adjusted odds ratio 2.35; 95% confidence interval [CI] 1.18-4.81; P=0.02). Binomial logistic regression revealed that achieving mTICI 2c/3 was significantly associated with higher odds of a favorable 90-day outcome (odds ratio 2.14; 95% CI 1.07-4.41; P=0.04)., Conclusion: In patients with low ASPECTS, achieving an mTICI 2c/3 score after MT is associated with a more favorable 90-day outcome. These findings suggest that mTICI 2c/3 is a better target for MT than mTICI 2b in patients with low ASPECTS.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1 ) identify patients with the currently accepted conceptual framework for ARDS, 2 ) facilitate rapid ARDS diagnosis for clinical care and research, 3 ) be applicable in resource-limited settings, 4 ) be useful for testing specific therapies, and 5 ) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1 ) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2 ) use Pa O 2 :Fi O 2  ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry Sp O 2 :Fi O 2  ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3 ) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4 ) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Background: Recent clinical trials have shown that mechanical thrombectomy is superior to medical management for large vessel occlusion for up to 24 hours from onset. Our objective is to examine the safety and efficacy of thrombectomy beyond the standard of care window., Methods: A retrospective review was undertaken of the multicenter Stroke Thrombectomy and Aneurysm Registry (STAR). We identified patients who underwent mechanical thrombectomy for large vessel occlusion beyond 24 hours. We selected a matched control group from patients who underwent thrombectomy in the 6-24-hour window. We used functional independence at 3 months as our primary outcome measure., Results: We identified 121 patients who underwent thrombectomy beyond 24 hours and 1824 in the 6-24-hour window. We selected a 2:1 matched group of patients with thrombectomy 6-24 hours as a comparison group. Patients undergoing thrombectomy beyond 24 hours were less likely to be independent at 90 days (18 (18.8%) vs 73 (34.9%), P=0.005). They had higher odds of mortality at 90 days in the adjusted analysis (OR 2.34, P=0.023). Symptomatic intracerebral hemorrhage and other complications were similar in the two groups. In a multivariate analysis only lower number of attempts was associated with good outcomes (OR 0.27, P=0.022)., Conclusions: Mechanical thrombectomy beyond 24 hours appears to be safe and tolerable with no more hemorrhages or complications compared with standard of care thrombectomy. Outcomes and mortality in this time window are worse compared with an earlier time window, but the rates of good outcomes may justify this therapy in selected patients., Competing Interests: Competing interests: PK: consultant for Stryker NV and Imperative Care. On the editorial board of JNIS. DRG: Balt Italy: Consultant, Microvention Europe: Consultant, Penumbra Inc: Consultant. AMS: Penumbra: Research support, Consultant. Stryker: Research support, Consultant. Cerenovus: Consultant. Terumo: Consultant. IschemaView Inc/Rapid AI: Research support, Consultant. ASA: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker Research support from Balt, Medtronic, Microvention, Penumbra and Siemens Shareholder Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Mentice, Neurogami, Serenity, Synchron, Triad Medical, Vastrax, VizAI. RDL: Consultant - Imperative Care, Stryker, Cerenovus, Spartan Micro. Research support – Siemens. On the editorial board of JNIS. ML: On the editorial board of JNIS. MM: On the editorial board of JNIS. JM: Consultant Stryker. On the editorial board of JNIS. MSP: Clinical Events Committee/Consultant for Medtronic. AP: consultant for Stryker and Depuy Synthes. ES: Consultant for Medtronic/Microvention/Rapid Medical., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aggregation of amyloid-β peptide (Aβ) is hypothesized to be the primary cause of Alzheimer's disease (AD) progression. Aβ aggregation has been widely studied using conventional sensing tools like emission fluorescence, electron microscopy, mass spectroscopy, and circular dichroism. However, none of these techniques can provide cost-efficient, highly sensitive quantification of Aβ aggregation kinetics at the molecular level. Among the influences on Aβ aggregation of interest to disease progression is the acceleration of Aβ aggregation by acetylcholinesterase (AChE), which is present in the brain and inflicts the fast progression of disease due to its direct interaction with Aβ. In this work, we demonstrate the ability of a biological nanopore to map and quantify AChE accelerated aggregation of Aβ monomers to mixed oligomers and small soluble aggregates with single-molecule precision. This method will allow future work on testing direct and indirect effects of therapeutic drugs on AChE accelerated Aβ aggregation as well as disease prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objective: Burnout in healthcare professionals (HCPs) is a pressing issue in healthcare. We report the long-term impact of our previous creative arts therapy (CAT) intervention for reducing psychological distress in HCPs., Methods: Healthcare professionals were randomized to CAT intervention or control group. The CAT group completed surveys evaluating symptoms of psychological distress at 4 months, 8 months, and 1 year postintervention, whereas the control group completed surveys at the 1-year mark., Results: The CAT group demonstrated sustained improvement in distress scores for anxiety, depression, and affect at 4 and 8 months postintervention. At the 12-month mark, the CAT group exhibited improvements in anxiety, depression, and affect compared with the control group., Conclusion: Creative arts therapy has lasting benefits for HCPs. Long-term follow-ups are crucial for assessing sustainability, and further investigation should focus on disseminating and implementing CAT programs for HCPs., Competing Interests: Conflict of Interest Disclosure: All authors report no conflict of interest., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Invasive mechanical ventilation can worsen lung injury. Ventilator dyssynchrony (VD) may propagate ventilator-induced lung injury (VILI) and is challenging to detect and systematically monitor because each patient takes approximately 25,000 breaths a day yet some types of VD are rare, accounting for less than 1% of all breaths. Therefore, we sought to develop and validate accurate machine learning (ML) algorithms to detect multiple types of VD by leveraging esophageal pressure waveform data to quantify patient effort with airway pressure, flow, and volume data generated during mechanical ventilation, building a computational pipeline to facilitate the study of VD., Materials and Methods: We collected ventilator waveform and esophageal pressure data from 30 patients admitted to the ICU. Esophageal pressure allows the measurement of transpulmonary pressure and patient effort. Waveform data were cleaned, features considered essential to VD detection were calculated, and a set of 10,000 breaths were manually labeled. Four ML algorithms were trained to classify each type of VD: logistic regression, support vector classification, random forest, and XGBoost., Results: We trained ML models to detect different families and seven types of VD with high sensitivity (>90% and >80%, respectively). Three types of VD remained difficult for ML to classify because of their rarity and lack of sample size. XGBoost classified breaths with increased specificity compared to other ML algorithms., Discussion: We developed ML models to detect multiple types of VD accurately. The ability to accurately detect multiple VD types addresses one of the significant limitations in understanding the role of VD in affecting patient outcomes., Conclusion: ML models identify multiple types of VD by utilizing esophageal pressure data and airway pressure, flow, and volume waveforms. The development of such computational pipelines will facilitate the identification of VD in a scalable fashion, allowing for the systematic study of VD and its impact on patient outcomes.

Background: Reducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy., Methods: This is a retrospective review of the Stroke Thrombectomy and Aneurysm Registry (STAR) database. All patients who underwent AIS thrombectomy with available ICH data were included. Multivariable regression models were developed to identify predictors of ICH after thrombectomy. Subgroup analyses were performed stratified by symptom status and European Cooperative Acute Stroke Study (ECASS) grade., Results: The study cohort comprised 6860 patients. Any ICH and symptomatic ICH (sICH) occurred in 25% and 7% of patients, respectively. Hemorrhagic infarction 1 (HI1) occurred in 36%, HI2 in 24%, parenchymal hemorrhage 1 (PH1) in 22%, and PH2 in 17% of patients classified by ECASS grade. Intraprocedural complications independently predicted any ICH (OR 3.8083, P<0.0001), PH1 (OR 1.9053, P=0.0195), and PH2 (OR 2.7347, P=0.0004). Race also independently predicted any ICH (black: OR 0.5180, P=0.0017; Hispanic: OR 0.4615, P=0.0148), sICH (non-white: OR 0.4349, P=0.0107), PH1 (non-white: OR 3.1668, P<0.0001), and PH2 (non-white: OR 1.8689, P=0.0176), with white as the reference. Primary mechanical thrombectomy technique also independently predicted ICH. ADAPT (A Direct Aspiration First Pass Technique) was a negative predictor of sICH (OR 0.2501, P<0.0001), with stent retriever as the reference., Conclusions: This study identified ICH risk factors after AIS thrombectomy using real-world data. There was a propensity towards a reduced sICH risk with direct aspiration. Procedural complications and ethnicity were predictors congruent between categories of any ICH, sICH, PH1, and PH2. Further investigation of technique and ethnicity effects on ICH and outcomes after AIS thrombectomy is warranted., Competing Interests: Competing interests: PK, JRM, MM and MRL are members of the editorial board of JNIS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Monitoring hand hygiene compliance in the ambulatory setting remains a challenge because a healthcare trained observer loses line of sight once the examination room door closes. This quality improvement project focused on the implementation of a hand hygiene compliance improvement programme that is amenable to the routines and work flows of the ambulatory setting., Methods: After a review of the literature, nursing leadership and infection prevention implemented the 'patient as the observer' hand hygiene programme across 32 ambulatory practices., Results: Patients completed 281,000 observations with an overall compliance rate of ≥90%. The average overall compliance rate by role was 91% for providers, 89% for nurses, and 91% for medical assistants/technicians/others. A 92% compliance average was noted 'before caring for you' and 89% 'after caring for you' for providers, 90% and 87% for nurses, and 92% and 89% for medical assistants/technicians/others., Discussion: This study demonstrated that the implementation of a hand hygiene compliance improvement programme using the patient as the observer can be adopted successfully in the ambulatory setting., Conclusion: Hand hygiene compliance can be monitored effectively in the ambulatory setting with the involvement of the patient as the observer., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore if patient characteristics (pre-existing comorbidity, age, sex, and illness severity) modify the effect of physical rehabilitation (intervention vs control) for the coprimary outcomes health-related quality of life (HRQoL) and objective physical performance using pooled individual patient data from randomized controlled trials (RCTs)., Data Sources: Data of individual patients from four critical care physical rehabilitation RCTs., Study Selection: Eligible trials were identified from a published systematic review., Data Extraction: Data sharing agreements were executed permitting transfer of anonymized data of individual patients from four trials to form one large, combined dataset. The pooled trial data were analyzed with linear mixed models fitted with fixed effects for treatment group, time, and trial., Data Synthesis: Four trials contributed data resulting in a combined total of 810 patients (intervention n = 403, control n = 407). After receiving trial rehabilitation interventions, patients with two or more comorbidities had HRQoL scores that were significantly higher and exceeded the minimal important difference at 3 and 6 months compared with the similarly comorbid control group (based on the Physical Component Summary score (Wald test p = 0.041). Patients with one or no comorbidities who received intervention had no HRQoL outcome differences at 3 and 6 months when compared with similarly comorbid control patients. No patient characteristic modified the physical performance outcome in patients who received physical rehabilitation., Conclusions: The identification of a target group with two or more comorbidities who derived benefits from the trial interventions is an important finding and provides direction for future investigations into the effect of rehabilitation. The multimorbid post-ICU population may be a select population for future prospective investigations into the effect of physical rehabilitation., Competing Interests: Dr. Puthucheary reports honorarium and speaker fees from Baxter, Faraday Pharmaceuticals, Lyric Pharmaceuticals, Fresenius-Kabi, Nestle, Orion, GlaxoSmithKline, and Nutritica. Dr. Files reports consulting fees from Cytovale. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Real-world evidence (RWE) research helps determine whether outcomes observed in clinical trials happen in real-life clinical practice. RWE research may help patients receive more appropriate treatment, closer to their needs and wishes. RWE for metastatic colorectal cancer is currently limited. The PROMETCO RWE study is an important example of an ongoing initiative that focuses on patient-reported outcomes in metastatic colorectal cancer. Patients play an active role throughout the RWE research process, including study design, participation and results dissemination. This involvement can encourage greater patient empowerment through active engagement, potentially resulting in various benefits that can lead to improved clinical outcomes. Greater patient engagement can increase involvement in RWE, helping more patients to access the benefits of RWE research. Clinical Trial Registration: NCT03935763 (ClinicalTrials.gov).

Introduction and Hypothesis: The incidence of trocar bladder puncture during midurethral sling (MUS) surgery varies widely. We aim to further characterize risk factors for bladder puncture and examine its long-term impact on storage and emptying., Methods: This is an Institutional Review Board-approved, retrospective chart review of women who underwent MUS surgery at our institution from 2004 to 2018 with ≥12 months of follow-up. Unless prolonged catheterization was necessary, a voiding trial was performed prior to discharge, or the next morning in outpatients, regardless of puncture. Preoperative and postoperative details were obtained from office charts and operative records., Results: Of 1,500 women, 1,063 (71%) had retropubic (RP) and 437 (29%) had transobturator MUS surgery. Mean follow-up was 34 months. Thirty-five women (2.3%) sustained a bladder puncture. RP approach and lower BMI were significantly associated with puncture. No statistical association was found between bladder puncture and age, previous pelvic surgery, or concomitant surgery. Mean day of discharge and day of successful voiding trial were not statistically different between the puncture and nonpuncture groups. There was no statistically significant difference in de novo storage and emptying symptoms between the two groups. Fifteen women in the puncture group had cystoscopy during follow-up and none had bladder exposure. Level of the resident performing trocar passage was not associated with bladder puncture., Conclusions: Lower BMI and RP approach are associated with bladder puncture during MUS surgery. Bladder puncture is not associated with additional perioperative complications, long-term urinary storage/voiding sequelae, or delayed bladder sling exposure. Standardized training minimizes bladder punctures in trainees of all levels., (© 2023. The International Urogynecological Association.)

Background: Sepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis., Methods: We genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets., Results: Among AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008-0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (P adjusted <0.0005 and 0.0006, respectively), suggesting a role in increased risk of renal dysfunction. In contrast, among EA ARDS patients, the missense variant rs17011368 (I703V) was associated with enhanced mortality at 60-days (P < 0.038). We found higher serum XOR activity in 143 sepsis patients (54.5 ± 57.1 mU/mL) compared to 31 controls (20.9 ± 12.4 mU/mL, P = 1.96 × 10 - 13 ). XOR activity was associated with the lead variant rs185925 among AA sepsis patients with ARDS (P < 0.005 and P adjusted <0.01). Multifaceted functions of prioritized XDH variants, as suggested by various functional annotation tools, support their potential causality in sepsis., Conclusions: Our findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS., (© 2023. The Author(s).)

Objectives: To develop a brief teamwork measure and determine how teamwork relates to provider experience, burnout, and work intentions., Study Design: Survey of clinicians., Methods: We analyzed data from Optum's 2019 biannual clinician survey, including a validated burnout measure and measures of provider experience and intent to stay. A 6-item measure of team effectiveness (TEAM) focused on efficiency, communication, continuous improvement, and leadership. Construct validity was assessed with content, reliability, and correlation with burnout. Generalized estimating equations with robust SEs determined relationships among TEAM score, provider experience, and intent to stay, controlling for demographics, clustering, and practice factors., Results: Of 1500 physicians and advanced practice clinicians (1387 with complete data; response rate 56%), there were 58% in primary care; 57% were women, and 38% identified as Asian, Black/Hispanic, or another race/ethnicity other than White non-Hispanic. Burnout was present in 30%. The Cronbach α was excellent (0.86), and TEAM correlated with the validated burnout measure (adjusted odds ratio [OR] of lower burnout with high TEAM score, 0.28; 95% CI, 0.19-0.40; P < .0001). Clinicians with TEAM scores of at least 4 were more likely to have positive provider experiences (79% favorable vs 24% with low TEAM score; P < .001), had lower burnout rates (17% vs 44%%; P < .001), and more often intended to stay (93% vs 65%; P < .001). TEAM index score was strongly associated with provider experience (adjusted OR, 11.72; 95% CI, 8.11-16.95; P < .001) and intent to stay (adjusted OR, 7.24; 95% CI, 5.34-9.83; P < .001)., Conclusions: The TEAM index is related to provider experience, burnout, and intent to stay, and it may help organizations optimize clinical work environments.

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research., (© 2023. The Author(s).)

This study explored how frequent gamblers perceive gambling marketing and the role they feel it has in their gambling behaviour. Ten frequent gamblers participated in semi-structured interviews oriented around their experiences of gambling marketing. An interpretative phenomenological analysis of the data led to three overarching themes: exploiting gambling marketing for personal gain; gambling marketing as a test of self-control; and safer gambling messages marketing perceived as ineffective. These themes encapsulated participants' views of gambling marketing as something they could take advantage of to increase their own gambling success. Marketing was also perceived as a test of self-control among self-identified experienced gamblers, although identified as a risk to those who are considered more vulnerable. Finally, safer gambling messages included within marketing was considered ineffective due to perceived insincerity and being seen as an 'afterthought' by marketers. In support of previous research, the current investigation highlights concerning narratives around self-control and perceived risk, as encapsulated within gambling marketing, and these are evident in the perceptions of frequent gamblers. Given gamblers' perceived lack of effectiveness of current safer gambling messages within marketing, future research should explore new avenues for safer gambling promotion., Competing Interests: The study was carried out as a part of the lead authors’ (SH) PhD studies. The PhD was funded by GambleAware. No other author has competing interests to declare., (Copyright: © 2023 Houghton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Long-duration gamma-ray bursts (GRBs) are powerful cosmic explosions, signaling the death of massive stars. Among them, GRB 221009A is by far the brightest burst ever observed. Because of its enormous energy ( E iso ≈ 10 55 erg) and proximity ( z ≈ 0.15), GRB 221009A is an exceptionally rare event that pushes the limits of our theories. We present multiwavelength observations covering the first 3 months of its afterglow evolution. The x-ray brightness decays as a power law with slope ≈ t -1.66 , which is not consistent with standard predictions for jetted emission. We attribute this behavior to a shallow energy profile of the relativistic jet. A similar trend is observed in other energetic GRBs, suggesting that the most extreme explosions may be powered by structured jets launched by a common central engine.

Background: Research suggests that the ingestion or aroma of rosemary enhances cognitive ability in both rodents and humans. However, how rosemary facilitates cognition and the precise therapeutic impacts on information processing remains unclear., Hypothesis/purpose: This pilot study used the temporal precision of event-related potentials (ERPs) to examine the cognitive-enhancing benefits of a rosemary drink. Neural markers of sustained attention were used as indices to explore whether rosemary facilitates concentration in general or the allocation of resources to task-relevant information only., Study Design and Methods: In a between-subject design (rosemary vs water control drink), 48 adults performed a 3-stimulus visual oddball task. Participants differentiated between rare target stimuli (index of task-relevant attentional processes; P3b ERP) embedded in a train of frequent stimuli. The presentation of an infrequent novel stimulus was also included (index of task-irrelevant stimulus processing; P3a ERP). Throughout the session, electroencephalograms (EEG) were collected and time-locked to the presentation of the target (P3b) and novel (P3a) stimulus types., Results: The primary analyses revealed facilitation of the P3a in particular with a medium Cohen's effect size reported. The investigation of the P3b component, although less reliable, also had a medium effect. The subsidiary consideration of the association between behaviour and the ERPs provided a further level of explanation regarding the therapeutic effect of rosemary on cognition. Indeed, the pattern of associations was suggestive of strategy differences during the performance of the task across the treatment group., although these data should be treated with caution., Conclusions: These pilot data provide critical insights into the utility of rosemary to facilitate different aspects of attention. In particular, data are consistent with rosemary providing additional attentional resources to enhance the processing of stimuli we encounter, irrespective of task relevance. Indeed, the enhancement of both P3a and P3b components following rosemary administration may indicate that the herb enhances the processing of all stimuli in the environment. We argue for the use of both behavioural and EEG methods to explore the therapeutic effects of herbal compounds., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Riby et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Psychological distress symptoms are common among patients recently hospitalized with cardiorespiratory failure, yet there are few effective postdischarge therapies that are relevant to their experiences. Objectives: To determine the feasibility and clinical impact of two different versions of a month-long self-guided mobile app-based coping skills program called Blueprint in comparison to usual care (UC) control. Methods: Patients hospitalized with a serious cardiopulmonary diagnoses were recruited from adult intensive care units and stepdown units at a large academic medical center. Participants with elevated psychological distress symptoms just after discharge were randomized in a 1:1:1 ratio to Blueprint with a therapist (BP/therapist), Blueprint without a therapist (BP/no therapist), or UC control. All study procedures were conducted remotely. Blueprint is a self-guided, symptom-responsive, mobile app-based adaptive coping skills program with 4 themed weeks with different daily audio, video, and text content. Participants completed surveys via the app platform at baseline and 1 and 3 months later. The primary outcome was feasibility. Additional outcomes included the HADS (Hospital Anxiety and Depression Scale) total score, the PTSS (Post-Traumatic Stress Scale), and a 100-point quality of life visual analog scale. Results: Of 63 patients who consented, 45 (71%) with elevated distress were randomized to BP/therapist ( n  = 16 [36%]), BP/no therapist ( n  = 14 [31%]), and UC ( n  = 15 [33%]). Observed rates were similar to target feasibility benchmarks, including consented patients who were randomized (71.4%), retention (75.6%), and intervention adherence (97% with weekly use). Estimated mean differences (95% confidence intervals) at 1 month compared with baseline included: HADS total (BP/therapist, -3.8 [-6.7 to -0.6]; BP/no therapist, -4.2 [-7.6 to -0.0]; UC, -3.4 [-6.6 to 0.2]); PTSS (BP/therapist, -6.7 [-11.3 to -2.1]; BP/no therapist, -9.1 [-14.4 to -3.9]; UC, -4.2 [-10.8 to 2.3]); and quality of life (BP/therapist, -4.5 [-14.3 to 4.6]; BP/no therapist, 14.0 [-0.9 to 29.0]; UC, 8.7 [-3.5 to 20.9]). Conclusions: Among survivors of cardiorespiratory failure, a mobile app-based postdischarge coping skills training intervention demonstrated evidence of feasibility and clinical impact compared with UC control. A larger trial is warranted to test the efficacy of this approach. Clinical trial registered with ClinicalTrials.gov (NCT04329702).

Background: Pelvic organ prolapse (POP) refers to symptomatic descent of the vaginal wall. To reduce surgical failure rates, surgical correction can be augmented with the insertion of polypropylene mesh. This benefit is offset by the risk of mesh complication, predominantly mesh exposure through the vaginal wall. If mesh placement is under consideration as part of prolapse repair, patient selection and counseling would benefit from the prediction of mesh exposure; yet, no such reliable preoperative method currently exists. Past studies indicate that inflammation and associated cytokine release is correlated with mesh complication. While some degree of mesh-induced cytokine response accompanies implantation, excessive or persistent cytokine responses may elicit inflammation and implant rejection., Objective: Here, we explore the levels of biomaterial-induced blood cytokines from patients who have undergone POP repair surgery to (1) identify correlations among cytokine expression and (2) predict postsurgical mesh exposure through the vaginal wall., Methods: Blood samples from 20 female patients who previously underwent surgical intervention with transvaginal placement of polypropylene mesh to correct POP were collected for the study. These included 10 who experienced postsurgical mesh exposure through the vaginal wall and 10 who did not. Blood samples incubated with inflammatory agent lipopolysaccharide, with sterile polypropylene mesh, or alone were analyzed for plasma levels of 13 proinflammatory and anti-inflammatory cytokines using multiplex assay. Data were analyzed by principal component analysis (PCA) to uncover associations among cytokines and identify cytokine patterns that correlate with postsurgical mesh exposure through the vaginal wall. Supervised machine learning models were created to predict the presence or absence of mesh exposure and probe the number of cytokine measurements required for effective predictions., Results: PCA revealed that proinflammatory cytokines interferon gamma, interleukin 12p70, and interleukin 2 are the largest contributors to the variance explained in PC 1, while anti-inflammatory cytokines interleukins 10, 4, and 6 are the largest contributors to the variance explained in PC 2. Additionally, PCA distinguished cytokine correlations that implicate prospective therapies to improve postsurgical outcomes. Among machine learning models trained with all 13 cytokines, the artificial neural network, the highest performing model, predicted POP surgical outcomes with 83% (15/18) accuracy; the same model predicted POP surgical outcomes with 78% (14/18) accuracy when trained with just 7 cytokines, demonstrating retention of predictive capability using a smaller cytokine group., Conclusions: This preliminary study, incorporating a sample size of just 20 participants, identified correlations among cytokines and demonstrated the potential of this novel approach to predict mesh exposure through the vaginal wall following transvaginal POP repair surgery. Further study with a larger sample size will be pursued to confirm these results. If corroborated, this method could provide a personalized medicine approach to assist surgeons in their recommendation of POP repair surgeries with minimal potential for adverse outcomes., (©Mihyun Lim Waugh, Nicholas Boltin, Lauren Wolf, Jane Goodwin, Patti Parker, Ronnie Horner, Matthew Hermes, Thomas Wheeler, Richard Goodwin, Melissa Moss. Originally published in JMIR Perioperative Medicine (http://periop.jmir.org), 31.05.2023.)

Despite the progress made in identifying cellular factors and mechanisms that predict progression and metastasis, breast cancer remains the second leading cause of death for women in the US. Using The Cancer Genome Atlas and mouse models of spontaneous and invasive mammary tumorigenesis, we identified that loss of function of interferon regulatory factor 5 (IRF5) is a predictor of metastasis and survival. Histologic analysis of Irf5 -/- mammary glands revealed expansion of luminal and myoepithelial cells, loss of organized glandular structure, and altered terminal end budding and migration. RNA-seq and ChIP-seq analyses of primary mammary epithelial cells from Irf5 +/+ and Irf5 -/- littermate mice revealed IRF5-mediated transcriptional regulation of proteins involved in ribosomal biogenesis. Using an invasive model of breast cancer lacking Irf5 , we demonstrate that IRF5 re-expression inhibits tumor growth and metastasis via increased trafficking of tumor infiltrating lymphocytes and altered tumor cell protein synthesis. These findings uncover a new function for IRF5 in the regulation of mammary tumorigenesis and metastasis., Highlights: Loss of IRF5 is a predictor of metastasis and survival in breast cancer.IRF5 contributes to the regulation of ribosome biogenesis in mammary epithelial cells.Loss of IRF5 function in mammary epithelial cells leads to increased protein translation.

Rationale: Family members of critically ill patients with coronavirus disease (COVID-19) have described increased symptoms of posttraumatic stress disorder (PTSD). Little is known about how these symptoms may change over time. Objectives: We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12 months. Methods: This prospective, multisite observational cohort study recruited participants at 12 hospitals in five states. Calls were made to participants at 3-4 months, 6 months, and 12 months after patient admission to the intensive care unit. Results: There were 955 eligible family members, of whom 330 (53.3% of those reached) consented to participate. Complete longitudinal data was acquired for 115 individuals (34.8% consented). PTSD symptoms were measured by the IES-6 (Impact of Events Scale-6), with a score of at least 10 identifying significant symptoms. At 3 months, the mean IES-6 score was 11.9 ± 6.1, with 63.6% having significant symptoms, decreasing to 32.9% at 1 year (mean IES-6 score, 7.6 ± 5.0). Three clusters of symptom evolution emerged over time: persistent symptoms (34.8%, n  = 40), recovered symptoms (33.0%, n  = 38), and nondevelopment of symptoms (32.2%, n  = 37). Although participants identifying as Hispanic demonstrated initially higher adjusted IES-6 scores (2.57 points higher [95% confidence interval (CI), 1.1-4.1; P  < 0.001]), they also demonstrated a more dramatic improvement in adjusted scores over time (4.7 greater decrease at 12 months [95% CI, 3.2-6.3; P  < 0.001]). Conclusions: One year later, some family members of patients with COVID-19 continue to experience significant symptoms of PTSD. Further studies are needed to better understand how various differences contribute to increased risk for these symptoms.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.

Objectives: To assess the rates of failed insertion, expulsion, and perforation when intrauterine device (IUD) insertions were done by newly trained clinicians, and to examine factors that may affect these outcomes., Study Design: We evaluated skill-based outcomes following IUD insertion at 12 African sites in a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial. Before trial initiation, we provided competency-based IUD training to clinicians and offered ongoing clinical support. We used Cox proportional hazards regression to examine factors associated with expulsion., Results: Among 2582 IUD acceptors who underwent first attempted IUD insertion, 141 experienced insertion failure (5.46%) and seven had uterine perforation (0.27%). Perforation was more common among breastfeeding women within three months postpartum (0.65%) compared with non-breastfeeding women (0.22%). We recorded 493 expulsions (15.5 per 100 person-years, 95% confidence interval [CI] 14.1─16.9): 383 partial and 110 complete. The risk of IUD expulsion was lower among women older than 24 years (aHR 0.63, 95% CI 0.50─0.78) and may be higher among nulliparous women. (aHR 1.65, 95% CI 0.97─2.82). Breastfeeding (aHR 0.94, 95% CI 0.72─1.22) had no significant effect on expulsion. IUD expulsion rate was highest during the first three months of the trial., Conclusions: IUD insertion failure and uterine perforation rates in our study were comparable to those reported in the literature. These results suggest that training, ongoing support, and opportunities to apply new skills were effective in ensuring good clinical outcomes for women receiving IUD insertion by newly trained providers., Implications: Data from this study support recommendations to program managers, policymakers, and clinicians that IUDs can be inserted safely in resource-constrained settings when providers receive appropriate training and support., (© 2023 The Author(s).)

Tissue adhesives constitute a great possibility to improve conventional wound closure. In contrast to sutures, they enable nearly immediate hemostasis and can prevent fluid or air leaks. In the present study, a poly(ester)urethane-based adhesive was investigated which already proved to be suitable for different indications, such as reinforcing vascular anastomosis and sealing liver tissue. Using in vitro and in vivo setups, the degradation of the adhesives was monitored over a period of up to 2 years, to evaluate long-term biocompatibility and determine degradation kinetics. For the first time, the complete degradation of the adhesive was documented. In subcutaneous locations, tissue residues were found after 12 months and in intramuscular locations, tissue degradation was complete after about 6 months. A detailed histological evaluation of the local tissue reaction revealed good biocompatibility throughout the different degradation stages. After full degradation, complete remodeling to physiological tissue was observed at the implant locations. In addition, this study critically discusses common issues related to the assessment of biomaterial degradation kinetics in the context of medical device certification. This work highlighted the importance and encouraged the implementation of biologically relevant in vitro degradation models to replace animal studies or at least reduce the number of animals in preclinical testing prior to clinical studies. Moreover, the suitability of frequently used implantation studies based on ISO 10993-6 at standard locations was critically discussed, especially in light of the associated lack of reliable predictions for degradation kinetics at the clinically relevant site of implantation.