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Objective: X-linked adrenoleukodystrophy (ALD) is caused by mutations in ABCD1, a peroxisomal gene. More than half of males with an ABCD1 mutation develop inflammatory cerebral demyelination (cALD), but underlying mechanisms remain unknown and therapies are limited. We sought to develop and characterize a mouse model of cALD to facilitate study of disease mechanisms and therapy development., Methods: We used immunoassays and immunohistochemistry to assess novel (interleukin 18 [IL-18]) and established molecular markers in cerebrospinal fluid (CSF) and postmortem brain tissue from cALD patients. We generated a cALD phenotype in Abcd1-knockout mice using a 2-hit method that combines cuprizone and experimental autoimmune encephalomyelitis models. We then used magnetic resonance imaging (MRI) and immunohistochemistry to assess the fidelity of cALD molecular markers in the mice., Results: Human and mouse cALD lesions shared histologic features of myelin phagocytosis, myelin loss, abundant microglial activation, T and B-cell infiltration, and astrogliosis. Compared to wild-type controls, Abcd1-knockout mice displayed more cerebral demyelination, blood-brain barrier disruption, and perivascular immune cell infiltration. This enhanced inflammatory response was associated with higher levels of fibrin deposition, oxidative stress, demyelination, and axonal injury. IL-18 immunoreactivity co-localized with perivascular monocytes/macrophages in both human and mouse brain tissue. In cALD patients, CSF IL-18 levels correlated with MRI lesion severity., Interpretation: Our results suggest loss of Abcd1 function in mice predisposes to more severe blood-brain barrier disruption, cerebral inflammation driven by the infiltration of peripheral immune cells, demyelination, and axonal damage, replicating human cALD features. This novel mouse model could shed light on cALD mechanisms and accelerate cALD therapy development. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Context: Families are vital providers and recipients of pediatric palliative care (PPC) services. Understanding the scope and nature of evidence at the intersection of family science and PPC research is necessary to develop family-focused interventions that enhance child and family health., Objectives: Explore and describe the family-level impact of pediatric serious illness., Methods: We conducted a librarian-assisted scoping review using Arskey and O'Malley's approach. We searched PubMed, Scopus, CINAHL, and EMBASE databases for empirical publications from 2016 to 2021 that focused on families navigating serious pediatric illness published in English. Two reviewers assessed eligibility, with discrepancies resolved by a third. We used Covidence and REDCap for data management and extraction., Results: We screened 10,983 abstracts; 309 abstracts were included in full text screening. The final group of 52 citations was analyzed by the entire team. Most research was conducted in Western Europe and North America. The perspectives of parents of children with cancer were most frequently described; voices of seriously ill youth and their siblings were less often presented. Most of the research was descriptive qualitative, followed by descriptive quantitative. Few studies were mixed methods, inferential, or interpretive. Studies most often described parent, youth, and family experience with illness and less often explored family processes and relationships. Irrespective of the approach (i.e., qualitative, quantitative), few studies focused on families as the analytic unit or used family-level analysis techniques. Study participants were usually from local dominant populations and less often from historically marginalized communities., Conclusion: The robust, descriptive, and individual-level evidence describing family impact of serious pediatric illness provides a solid foundation for future research priorities. Stronger integration of family techniques and diverse family voices in pediatric palliative care research can clarify family processes, illuminate structural barriers, and inform interventions that are responsive to family needs. These steps will enhance the education, policy, and clinical provision of PPC to all who would benefit, thereby advancing health equity for children living with serious illness and their families., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Sexual violence is a public health threat in the USA and past research has found that survivors who seek support and disclose their experiences tend to have greater positive outcomes, such as positive life changes, reduced post-traumatic stress disorder, and fewer depressive symptoms. While social media have become an important site of disclosure, over-moderation of sex and sexuality on social media platforms due to the passing of the Fight Online Sex Trafficking Act and the Stop Enabling Sex Traffickers Act may inadvertently lead to the removal of survivors' posts and hinder their ability to build communities of support. In line with critical discourse analysis, this study examined the discursive strategies utilized in online disclosures made by sexual violence survivors on the social media platform TikTok to determine if they make use of algospeak, a neologism referring to the strategy of misspelling words or using coded language to avoid detection and deletion by site moderators. Analysis of the data indicated that sexual violence survivors do make use of algospeak, as well as direct and indirect language, to share their disclosures, and that, while TikTok claims to provide space for survivors' stories, its guidelines and approach to language about sex and sexuality may create barriers to building supportive communities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neuroblastoma is a highly lethal malignancy of young children. Mesenchymal stromal cells (MSCs) may represent a novel cellular delivery vehicle due to their innate tumor-homing properties. We compared in vivo homing abilities of placental-derived MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) in an orthotopic neuroblastoma xenograft., Methods: 28 mice underwent direct implantation of neuroblastoma cells (cell line NB1643) into the adrenal gland followed by intraperitoneal injection of 5 × 10 6 MSCs (PMSC n = 13, BM-MSC n = 13, PBS controls n = 2). MSC migration was monitored with in vivo imaging system (IVIS) radiance measurements at multiple timepoints post-MSC injection. Necropsy timepoints were 72 h (n = 10) and 7 days (n = 16). Ex vivo imaging was performed on all adrenal masses and select organ tissues. Immunohistochemistry (IHC) assessed the presence of MSCs in tumors., Results: IVIS demonstrated initial diffuse signal that migrated to the left abdomen. Radiance decreased over time, but MSC signal persisted at day 7 in all animals. Ex vivo IVIS demonstrated signal in the adrenal tumor but not other organs. There was no significant difference in average ex vivo adrenal mass radiance between MSC groups (p = 0.74). IHC confirmed presence of both MSC types within the tumor., Conclusion: PMSCs and BM-MSCs successfully migrated to neuroblastoma tumor tissues in vivo without evidence of migration to other organs. MSCs migrate within 72 h and persisted within the tumor up to 7 days. There was no significant difference in homing capabilities of PMSCs compared to BM-MSCs, indicating that either cell type has potential as a drug delivery vehicle., Type of Study: Original Research., Level of Evidence: n/a., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lignin-containing cellulose nanofibrils (LCNFs) are mainly produced commercially from treated wood pulp, which can decrease some of the carbon-negative benefits of utilizing biomass feedstock. In this work, LCNFs are prepared from non-wood feedstocks, including agricultural residues such as hemp, wheat straw, and flax. These feedstocks allowed for the preparation of LCNFs with a variety of properties, including tailored hydrophobicity. The feedstocks and their subsequent LCNFs are extensively characterized to determine the roles that feedstocks play on the morphology and properties of their resultant LCNFs. The LCNFs were then incorporated into paper handsheets to study their usefulness in papermaking applications, which indicated good potential for the use of wheat straw LCNFs as a surface additive to improve the oil resistance coating.

Data sharing is increasingly an expectation in health research as part of a general move toward more open sciences. In the United States, in particular, the implementation of the 2023 National Institutes of Health Data Management and Sharing Policy has made it clear that qualitative studies are not exempt from this data sharing requirement. Recognizing this trend, the Palliative Care Research Cooperative Group (PCRC) realized the value of creating a de-identified qualitative data repository to complement its existing de-identified quantitative data repository. The PCRC Data Informatics and Statistics Core leadership partnered with the Qualitative Data Repository (QDR) to establish the first serious illness and palliative care qualitative data repository in the U.S. We describe the processes used to develop this repository, called the PCRC-QDR, as well as our outreach and education among the palliative care researcher community, which led to the first ten projects to share the data in the new repository. Specifically, we discuss how we co-designed the PCRC-QDR and created tailored guidelines for depositing and sharing qualitative data depending on the original research context, establishing uniform expectations for key components of relevant documentation, and the use of suitable access controls for sensitive data. We also describe how PCRC was able to leverage its existing community to recruit and guide early depositors and outline lessons learned in evaluating the experience. This work advances the establishment of best practices in qualitative data sharing., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: This study determined the performance characteristics of a quantitative glucose-6-phosphate dehydrogenase (G6PD) assay with automated lysis and evaluated the robustness of the operational workflow following implementation in a hospital laboratory., Methods: The G6PD activity was measured in whole blood using an enzymatic quantitative test on a Roche cobas c501 analyzer with onboard lysis configuration and normalized to hemoglobin (Hb). The performance characteristics of the method and stability of G6PD in whole blood collected in EDTA-containing tubes were evaluated, and the reference interval was established on a population of healthy individuals (n = 279). The robustness of this automated workflow for sample lysis was evaluated during validation and after implementation for routine clinical use for 18 months and in 2,181 patients., Results: The G6PD assay was linear from 0.7 to 16.5 U/g Hb. Inter- and intra-assay precision using control and patient samples was below 12%. The G6PD results correlated well with a reference laboratory method (r = 0.96, y = 0.9615x - 1.222). The reference interval in our population was 9.8 to 15.5 U/g Hb. There were no interferences by lipemia and icteria, although grossly hemolyzed specimens may be affected. The testing workflow requires analyzing samples within minutes from mixing and loading into the instrument to avoid sample sedimentation. Measures to repeat samples with Hb 8.0 g/dL or less identified sedimented samples. In our patient population, 10.6% and 5.8% of the total males and females tested were G6PD deficient, respectively., Conclusions: The G6PD assay with automated lysis is acceptable for patient testing. Several measures ensured the robustness of this workflow in a hospital laboratory., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: This study aims to appraise recommendations from an expert panel of surgical educators on optimizing surgical education and training in the setting of contemporary challenges., Background: The Blue Ribbon Committee (BRC II), a group of surgical educators, was convened to make recommendations to optimize surgical training considering the current changes in the landscape of surgical education. Surgical trainees were recruited to assess their impressions of the recommendations., Methods: A mixed-methods study design was employed, with a survey, followed by focus group interviews. Participating residents and fellows were recruited through a purposeful sampling approach. Descriptive statistics were applied to analyze the survey data, and a thematic data analysis on interview transcripts was employed., Results: The majority of trainee respondents (n=16) thought that all of the subcommittee recommendations should be included in the final BRC II recommendations and paper. According to the interviews, overall, the feedback from the trainees was positive, with particular excitement around work-life integration, education support and faculty development, and funding pitfalls. Some themes about concerns included a lack of clarity about the recommendations, concern about some recommendations being in conflict with one another, and a disconnect between the initial BRC II survey and the subsequent recommendations., Conclusions: The residents gathered for this focus group were encouraged by the thought, effort, and intention that gathered the surgical leaders across the country to make the recommendations. While there were areas the trainees wanted clarity on, the overall opinion was in agreement with the recommendations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neuroblastoma is a common pediatric malignancy with poor survival for high-risk disease. Mesenchymal stromal cells (MSCs) have innate tumor-homing properties, enabling them to serve as a cellular delivery vehicle, but MSCs have demonstrated variable effects on tumor growth. We compared how placental MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) affect proliferation of neuroblastoma (NB) cells in vitro., Methods: Indirect co-culture assessed proliferative effects of 18 MSCs (early-gestation PMSCs (n = 9), term PMSCs (n = 5), BM-MSCs (n = 4) on three high-risk NB cell lines (NB1643, SH-SY5Y, and CHLA90). Controls were NB cells cultured in media alone. Proliferation was assessed using MTS assay and measured by fold change (fc) over controls. PMSCs were sub-grouped by neuroprotective effect: strong (n = 7), intermediate (n = 3), and weak (n = 4). The relationship between MSC type, PMSC neuroprotection, and PMSC gestational age on NB cell proliferation was assessed., Results: NB cell proliferation varied between MSC groups. BM-MSCs demonstrated lower proliferative effects than PMSCs (fc 1.18 vs 1.44, p < 0.001). Neither gestational age nor neuroprotection significantly predicted degree of proliferation. Proliferative effects of MSCs varied among NB cell lines. BM-MSCs had less effect on CHLA90 (fc 1.01) compared to NB1643 (fc 1.33) and SH-SY5Y (fc 1.20). Only NB1643 showed a difference between early and term PMSCs (p = 0.04)., Conclusion: Effects of MSCs on NB cell proliferation vary by MSC source and NB cell line. BM-MSCs demonstrated lower proliferative effects than most PMSCs. MSC neuroprotection was not correlated with proliferation. Improved understanding of MSC proliferation-promoting mechanisms may provide valuable insight into selection of cells best suited as drug delivery vehicles., Level of Evidence: N/A., Type of Study: Original Research., (Published by Elsevier Inc.)

Secondary spinal cord injury (SCI) is characterized by increased cytokines and chemokines at the site of injury that have been associated with the development of neuropathic pain. Nearly 80% of SCI patients report suffering from chronic pain, which is poorly managed with available analgesics. While treatment with the FDA-approved β 2 -adrenergic receptor agonist, formoterol, improves various aspects of recovery post-SCI in vivo , its effects on cytokines, chemokines and neuropathic pain remain unknown. Female mice were subjected to moderate (60 kdyn) or severe (80 kdyn) SCI followed by daily treatment with vehicle or formoterol (0.3 mg/kg, i.p.) beginning 8h after injury. The expression of pro-inflammatory cytokines/chemokines, such as IP-10, MIP-1a, MCP-1, BCA-1 and NF-κB, was increased in the injury site of vehicle-treated mice 24h post-SCI, which was ameliorated with formoterol treatment, regardless of injury severity. Thermal hyperalgesia and mechanical allodynia, as measured by Hargreaves infrared apparatus and von Frey filaments, respectively, were assessed prior to SCI and then weekly beginning 21 days post injury (DPI). While all injured mice exhibited decreased withdrawal latency following thermal stimulation compared to baseline, formoterol treatment reduced this response ~15% by 35 DPI. Vehicle-treated mice displayed significant mechanical allodynia, as evidenced by a 55% decrease in withdrawal threshold from baseline. In contrast, mice treated with formoterol maintained a consistent withdrawal time at all times tested. These data indicate that formoterol reduces inflammation post-SCI, likely contributing to mitigation of neuropathic pain, and further supporting the therapeutic potential of this treatment strategy. Significance Statement Chronic pain is a detrimental consequence of spinal cord injury (SCI). We show that treatment with the FDA-approved drug formoterol after SCI decreases injury site pro-inflammatory chemo/cytokines and alters markers of glial cell activation and infiltration. Additionally, formoterol treatment improves locomotor function and body composition, and decreases lesion volume. Finally, formoterol treatment decreased mechanical allodynia and thermal hyperalgesia post-SCI. These data are suggestive of the mechanism of formoterol-induced recovery, and further indicate its potential as a therapeutic strategy for SCI., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

Background: To advance oncology treatment for adults, comprehensive understanding of how and why people decide to enroll in, remain in, and withdraw from cancer clinical trials is needed. While quantitative findings provide insights into these benefits and burdens, they provide limited understanding of how adults with cancer appraise their situation and approach decisions to undertake a clinical trial. The goal of this mixed methods analysis was to conceptualize participants' assessment of benefits and burdens related to cancer clinical trial participation., Materials and Methods: This sub-group analysis of 21 participants was part of a larger sequential, explanatory mixed methods study. We used Creamer's integrated approach to linking quantitative and qualitative data to assess convergence, with qualitative data explaining quantitative results. Participants were grouped into four categories based on quantitative benefit/burden scores and thematic analysis of their qualitative data was used to describe these categories., Results: Across groups participants varied in descriptions of benefits and burdens of cancer clinical trial participation and reasons for participating. Those reporting high benefit/low burden described "seizing the opportunity to participate;" those reporting low benefit/low burden described "taking responsibility" through trial participation; those reporting low benefit/high burden described how they were "willing to endure," and those with high benefit/high burden emphasized "deciding to act.", Conclusions: Participants' qualitative descriptions of benefits and burdens were more nuanced and dynamic than reflected in their quantitative ratings. Thus, current measures may be missing important concepts, such as logistic challenges of trial participation. Our results have implications for consenting procedures and decisional support guidance offered to patients and their caregivers.

Introduction: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines., Main Recommendations: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group., Changes in Management Resulting From the Guideline: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Over 18 million people worldwide were diagnosed with cancer in 2020, including over 150,000 people in Australia. Although improved early detection and treatment have increased the survival rates, cardiotoxic treatment and inadequate management of cardiovascular risk factors have resulted in cardiovascular disease (CVD) being one of the leading causes of non-cancer-related death and disability among cancer survivors. International guidelines outline the standards of care for CVD risk surveillance and management. However, Australian cardio-oncology policies and clinical guidelines are limited. There is increasing growth of cardio-oncology research in Australia and support from leading Australian professional bodies and advocacy and research networks, including the Cardiac Society of Australia and New Zealand, the Clinical Oncology Society of Australia, the National Heart Foundation of Australia, and the Australian Cardiovascular Alliance (ACvA). Thus, opportunities to drive multidisciplinary cardio-oncology initiatives are growing, including grant funding, position statements, and novel research to inform new policies. The ACvA has a unique flagship structure that spans the translational research pipeline from drug discovery to implementation science. This article aims to highlight how multidisciplinary cardio-oncology innovations could intersect with the seven ACvA flagships, and to showcase Australian achievements in cardio-oncology thus far. We summarise eight key priority areas for future cardio-oncology research that emerged. These strategies will strengthen cardio-oncology research and care in Australia, and drive new guidelines, policies, and government initiatives to ensure equity in health outcomes for all cardio-oncology patients., Competing Interests: Conflicts of Interest The authors are members of the Australian Cardiovascular Alliance (ACvA). K.D. is the CEO of the ACvA and G.F. was the ACvA President at the time of manuscript preparation and submission., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Family nursing researchers are charged with addressing the conceptual and methodological underpinnings of family research when developing family-focused interventions. Step-by-step guidance is needed that integrates current science of intervention development with family science and helps researchers progress from foundational work to experimental work with policy integration. The purpose of this manuscript is to provide pragmatic, evidence-based guidance for advancing family intervention research from foundational work through efficacy testing. Guidance regarding the development of family interventions is presented using the first three of Sidani's five-stage method: (a) foundational work to understand the problem targeted for change; (b) intervention development and assessment of acceptability and feasibility; and (c) efficacy testing. Each stage of family intervention development is described in terms of process, design considerations, and policy and practice implications. Examples are included to emphasize the family lens. This manuscript provides guidance to family scientists for intervention development and implementation to advance family nursing science and inform policy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Infectious disease outbreaks like Ebola and Covid-19 are increasing in frequency. They may harm reproductive, maternal and newborn health (RMNH) directly and indirectly. Sierra Leone experienced a sharp deterioration of RMNH during the 2014-16 Ebola epidemic. One possible explanation is that donor funding may have been diverted away from RMNH to the Ebola response., Methods: We analysed donor-reported data from the Organisation for Economic Cooperation and Development (OECD)'s Creditor Reported System (CRS) data for Sierra Leone before, during and after the 2014-16 Ebola epidemic to understand whether aid flows for Ebola displaced aid for RMNH. We estimated aid for Ebola using key term searches and manual review of CRS records. We estimated aid for RMNH by applying the Muskoka-2 algorithm to the CRS and analysing CRS purpose codes., Results: We find substantial increases in aid to Sierra Leone (from $484 million in 2013 to $1 billion at the height of the epidemic in 2015), most of which was earmarked for the Ebola response. Overall, Ebola aid was additional to RMNH funding. RMNH aid was sustained during the epidemic (at $42 m per year) and peaked immediately after (at $77 m in 2016). There is some evidence of a small displacement of RMNH aid from the UK during the period when its Ebola funding increased., Conclusions: Modest changes to RMNH donor aid patterns are insufficient to explain the severe decline in RMNH indicators recorded during the outbreak. Our findings therefore suggest the need for substantial increases in routine aid to ensure that basic RMNH services and infrastructure are strong before an epidemic occurs, as well as increased aid for RMNH during epidemics like Ebola and Covid-19, if reproductive, maternal and newborn healthcare is to be maintained at pre-epidemic levels., (© 2024. The Author(s).)

Background: A direct aspiration first pass technique (ADAPT) is an effective alternative to stent retriever thrombectomy for patients with large vessel occlusion (LVO). The PERFECT study evaluated direct aspiration with the EMBOVAC large bore aspiration catheter in patients with LVO strokes., Methods: PERFECT was a prospective, post-market, single-arm, multicenter, observational study of patients enrolled across 11 European centers between October 2020 and July 2022. Three direct aspiration passes with EMBOVAC were mandated before switching strategy. The primary endpoint was core-lab assessed successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b) post-procedure. Other outcomes included first pass mTICI ≥2c, independent 90-day modified Rankin Scale (mRS) evaluation, and symptomatic intracerebral hemorrhage (sICH) at 24 hours by a clinical events committee., Results: EMBOVAC was used in 100 patients (mean age 70.4±14.0 years, 59.0% (59/100) female). Final mTICI ≥2b was achieved in 98.0% (97/99), final mTICI ≥2b with no change in frontline therapy or thrombolytics use during the procedure was achieved in 87.9% (87/99), final mTICI ≥2c in 86.9% (86/99), and first pass mTICI ≥2c in 53.5% (53/99). sICH at 24 hours was 0%. The 90-day mRS ≤2 rate was 56.6% (56/99) and all-cause mortality was 12.9%. One device-related serious adverse event occurred within 90 days (1.0%)., Conclusions: PERFECT demonstrates that EMBOVAC achieves successful reperfusion rates and favorable clinical outcomes when used in the endovascular treatment of acute ischemic stroke (AIS) using a direct aspiration technique as first line therapy in a real-world setting in patients with AIS secondary to large vessel occlusion., Trial Registration: www., Clinicaltrials: gov Unique identifier: NCT04531904., Competing Interests: Competing interests: OJ: personal fees: Fa. Arcandis/Germany. GM: payment/honoraria for lectures, presentations, Speakers Bureaus, manuscript writing, educational events: Medtronic, Microvention; consulting fees: Stryker Neurovascular, Microvention Europe, Balt SAS, Sim and Size; paid lectures: Medtronic 675, Cerenovus, Bracco, Phenox. BG: consulting fees: Surge2surgery. HN: payment/honoraria for lectures, presentations, educational events: Acandis, Cerenovus, Phenox, Rapid medical. CC: payment/honoraria for lectures, presentations, Speakers bureaus, manuscript writing, educational events: Medtronic, Microvention, MIVI, Stryker. CL: proctoring/consultant services: Phenox; consultant services: Penumbra; travel and meeting expenses: Acandis, Penumbra; payment of honoraria for lectures and support for attending meetings: Phenox, Penumbra, Acandis. AS: employed by/holds shares: GSK. JF: research support: German Ministry of Science and Education, German Ministry of Economy and Innovation, German Research Foundation, European Union, Hamburgische Investitions-/ Förderbank, Medtronic, Microvention, Philips, Stryker; consultancy appointments: Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche, Route92, Stryker, Tonbridge, TG Medical; stock holdings: Tegus Medical, Vastrax, Eppdata. KD: academic grants: Science Foundation Ireland. MP, BE, AP, MZ, AM, KL: nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Electrochemical impedance spectroscopy can determine characteristics such as cell density, size, and shape. The development of an electrical impedance-based medical device to estimate acute ischemic stroke (AIS) clot characteristics could improve stroke patient outcomes by informing clinical decision making., Objectives: To assess how well electrical impedance combined with machine learning identified red blood cell (RBC)-rich composition of AIS clots ex vivo , which is associated with a successfully modified first-pass effect., Methods: A total of 253 clots from 231 patients who underwent thrombectomy in 5 hospitals in France, Japan, Serbia, and Spain between February 2021 and October 2023 were analyzed in the Clotbase International Registry. Electrical impedance measurements were taken following clot retrieval by thrombectomy, followed by Martius Scarlet Blue staining. The clot components were quantified via Orbit Image Analysis, and RBC percentages were correlated with the RBC estimations made by the electrical impedance machine learning model., Results: Quantification by Martius Scarlet Blue staining identified RBCs as the major component in clots (RBCs, 37.6%; white blood cells, 5.7%; fibrin, 25.5%; platelets/other, 30.3%; and collagen, 1%). The impedance-based RBC estimation correlated well with the RBC content determined by histology, with a slope of 0.9 and Spearman's correlation of r = 0.7. Clots removed in 1 pass were significantly richer in RBCs and clots with successful recanalization in 1 pass (modified first-pass effect) were richer in RBCs as assessed using histology and impedance signature., Conclusion: Electrical impedance estimations of RBC content in AIS clots are consistent with histologic findings and may have potential for clinically relevant parameters., (© 2024 The Author(s).)

Introduction : Thanks to advances in healthcare and technology, adolescents with medical complexity (AMC) and life-threatening conditions are living longer lives and may be expected to transition to adult health care. Yet, current systems and policies of transition care may not reflect their needs, those of their family, or the impact of social determinants of health. The goal of this study was to describe the relationship between social determinants of health and high-quality transition care. Methods : Retrospective cohort study of the 2019-2020 National Survey of Children's Health. The main outcome variable was any support for transition to adult health care. Independent variables were based on a social determinants of health framework. Weighted logistic regression was used to evaluate the association between social determinants and any support for transition to adult health care. Results : Final weighted sample included 444,915 AMC. AMC were distributed across income levels, most commonly lived in the South, and in supportive, resilient communities. More than 50% experienced adverse childhood events and less than 50% had adequate insurance. Less than one third received any transition support from providers; those who did reported time alone with the provider or active management. Social determinants related to missed days of school, community support/family context, and poverty were associated with both receipt and absence of transition care. Conclusion : AMC and their families navigate complex environments and associated stressors. Social determinants of health, particularly economic, community/social, and healthcare exert significant and nuanced influence. Such impacts should be incorporated into transition care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Gender gaps in physical activity (PA) exist with women being less active than men. Multiple cultural and psychosocial factors influence women's ability to successfully negotiate barriers to PA and other health promoting behaviors. The goal of this exploratory descriptive study was to better understand the daily experiences of mothers in making health promoting decisions for themselves and their families. Semi-structured interviews ( N  = 17) were conducted with rural dwelling mothers who were the primary caregivers of children in the home. Participants were asked to share their experiences with PA and other health behaviors, focusing on their motivators, barriers, and facilitators. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic content analysis. Emerging themes focused on 1) feeling internal and external pressures to prioritize family's needs over one's health, 2) family exerting both positive and negative influences on health choices, and 3) living in a rural community often resulting in a lack of opportunities to engage in physical activity and feelings of being isolated from social networks. To close the gender gap in PA, interventions should support mothers in navigating their multiple roles and competing demands while engaging in health promoting behaviors such as physical activity.

Background/aim: Neuroblastoma is a common childhood cancer with poor survival for children with high-risk disease, and ongoing research to improve outcomes is needed. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are reliable models for oncologic research; however, they are resource-intensive, expensive, and require significant expertise to develop and maintain. We developed an orthotopic xenograft murine model of neuroblastoma that utilizes cryopreserved banks of human neuroblastoma cell lines, requires minimal equipment, and is easily reproducible., Materials and Methods: The neuroblastoma cell line NB1643 was obtained from the Children's Oncology Group (COG) Childhood Cancer Repository. Nod-SCID-gamma (NSG) mice underwent orthotopic injection of 2x10 6 NB1643 cells suspended in 10 μl of collagen hydrogel directly into the adrenal gland via an open retroperitoneal surgical approach. Mice were monitored by ultrasound and in vivo imaging system (IVIS) until the tumor reached the volume of the ipsilateral kidney. Tumor identity was confirmed by necropsy and histologic analysis., Results: A total of 55 mice underwent surgery. Eight died due to anesthetic or surgical complications. 39/47 (78%) survivors grew primary adrenal tumors. Average anesthesia time was 30 min. Ultrasound and IVIS successfully characterized tumor growth in all mice. Average time to target tumor size was 5 weeks (range=3-9). Gross pathologic and histologic analysis confirmed adrenal tumors consistent with neuroblastoma in all mice with adrenal masses., Conclusion: A cell-derived orthotopic xenograft murine model can be successfully used to create an in vivo model of neuroblastoma. This model can be utilized in environments where PDX or GEMM models are not feasible., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hospice and palliative medicine (HPM) educators must often give up the satisfaction of working one-on-one with patients, to allow learners the opportunity to practice key communication skills and form their own therapeutic bonds with patients. Though the loss of that primary relationship with patients may feel challenging, educators may find new opportunity for professional impact and satisfaction by investing in their relationship with learners. This case discussion explores the challenges of bedside teaching in HPM, including the educator's looser connection with patients, need to withhold their own communication skills, and decision of when to interject into a trainee-patient conversation. We then propose strategies to help educators find renewed professional fulfillment in the teacher-learner relationship. By partnering intentionally with learners before, during, and after shared visits, inviting informal reflection between encounters, and preserving independent clinical time, we believe educators may cultivate a more sustainable and meaningful clinical teaching practice.

The VALID BP project was initiated to increase the availability of validated blood pressure measuring devices (BPMDs). The goal is to eliminate non validated BPMDs and minimise over- and underdiagnosis of hypertension caused by inaccurate readings. This study was undertaken to assess the potential return on investment in the VALID BP project. The Framework to Assess the Impact of Translational Health Research was applied to the VALID BP project. This paper focuses on the implementation of the cost benefit analysis aspect of this framework to monetise past research investment and model future research costs, implementation costs, and benefits. Analysis was based on reasoned assumptions about potential impacts from availability and use of validated BPMDs (assuming an end goal of 100% validated BPMDs available in Australia by 2028) and improved skills leading to more accurate BP measurement. After 5 years, with 20% attribution of benefits, there is a potential $1.14-$1.30 return for every dollar spent if the proportion of validated BPMDs and staff trained in proper BP measurement technique increased from 20% to 60%. After eight years (2020-2028) and assuming universal validation and training coverage, the returns would be between $2.70 and $3.20 per dollar spent (not including cost of side effects of unnecessary medication or downstream patient impacts from unmanaged hypertension). This modelled economic analysis indicates there will be positive downstream economic benefits if the availability of validated BPMDs is increased. The findings support ongoing efforts toward a universal regulatory framework for BPMDs and can be considered within more detailed future economic analyses., (© 2023. The Author(s).)

Objective: To evaluate gender differences in physical activity (PA), stress and resiliency during the COVID-19 pandemic. Participants: Students ( n  = 300) at a southeastern US university. Methods: Perceived Stress (PSS), Resiliency (BRS), Life Events (LEI), and PA were recorded via online survey in Summer 2020. PSS, BRS, LEI, and PA were compared between males and females. Two-way ANOVAs examined gender and frequency effects on PSS and BRS. Results: Females had lower BRS and higher PSS and LEI scores than males (all p  < .001). PSS/BRS scores were more strongly correlated with PA in males. Significant gender × frequency interactions were found for PSS (vigorous, p  = .03) and for BRS (moderate, p  = .049). There was a significant main effect of frequency for PSS with strength training ( p  < .001). Conclusions: Results suggest that interventions may be particularly needed for females and those with low PA levels.

Background: Lymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS., Methods: AIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots. Martius Scarlet Blue stain was used to identify the main histological components of the clots. Immunohistochemical staining was used to identify neutrophils, lymphocytes, macrophages, and NETs patterns. The cellular and histological components were quantified using Orbit Image Analysis software., Results: AT clots were larger, with more red blood cells and fewer WBCs than CE clots. AT clots had more lymphocytes and cryptogenic clots had fewer macrophages than other etiologies. Most significantly, CE clots showed higher expression of neutrophils and extracellular web-like NETs compared to AT and cryptogenic clots. There was also a significantly higher distribution of web-like NETs around the periphery of the CE clots while a mixed distribution was observed in AT clots., Conclusion: The difference in neutrophil and NETs expression in clots from different etiologies may provide insight into the mechanism of clot formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Somatosensory evoked potentials (SSEPs) help prognostication, particularly in patients with diffuse brain injury. However, use of SSEP is limited in critical care. We propose a novel, low-cost approach allowing acquisition of screening SSEP using widely available intensive care unit (ICU) equipment, specifically a peripheral "train-of-four" stimulator and standard electroencephalograph., Methods: The median nerve was stimulated using a train-of-four stimulator, and a standard 21-channel electroencephalograph was recorded to generate the screening SSEP. Generation of the SSEP was supported by visual inspection, univariate event-related potentials statistics, and a multivariate support vector machine (SVM) decoding algorithm. This approach was validated in 15 healthy volunteers and validated against standard SSEPs in 10 ICU patients. The ability of this approach to predict poor neurological outcome, defined as death, vegetative state, or severe disability at 6 months, was tested in an additional set of 39 ICU patients., Results: In each of the healthy volunteers, both the univariate and the SVM methods reliably detected SSEP responses. In patients, when compared against the standard SSEP method, the univariate event-related potentials method matched in nine of ten patients (sensitivity = 94%, specificity = 100%), and the SVM had 100% sensitivity and specificity when compared with the standard method. For the 49 ICU patients, we performed both the univariate and the SVM methods: a bilateral absence of short latency responses (n = 8) predicted poor neurological outcome with 0% FPR (sensitivity = 21%, specificity = 100%)., Conclusions: Somatosensory evoked potentials can reliably be recorded using the proposed approach. Given the very good but slightly lower sensitivity of absent SSEPs in the proposed screening approach, confirmation of absent SSEP responses using standard SSEP recordings is advised., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots., Methods: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot., Results: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts., Conclusion: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

In unconscious appearing patients with acute brain injury, wilful brain activation to motor commands without behavioural signs of command following, known as cognitive motor dissociation (CMD), is associated with functional recovery. CMD can be detected by applying machine learning to EEG recorded during motor command presentation in behaviourally unresponsive patients. Identifying patients with CMD carries clinical implications for patient interactions, communication with families, and guidance of therapeutic decisions but underlying mechanisms of CMD remain unknown. By analysing structural lesion patterns and network level dysfunction we tested the hypothesis that, in cases with preserved arousal and command comprehension, a failure to integrate comprehended motor commands with motor outputs underlies CMD. Manual segmentation of T2-fluid attenuated inversion recovery and diffusion weighted imaging sequences quantifying structural injury was performed in consecutive unresponsive patients with acute brain injury (n = 107) who underwent EEG-based CMD assessments and MRI. Lesion pattern analysis was applied to identify lesion patterns common among patients with (n = 21) and without CMD (n = 86). Thalamocortical and cortico-cortical network connectivity were assessed applying ABCD classification of power spectral density plots and weighted pairwise phase consistency (WPPC) to resting EEG, respectively. Two distinct structural lesion patterns were identified on MRI for CMD and three for non-CMD patients. In non-CMD patients, injury to brainstem arousal pathways including the midbrain were seen, while no CMD patients had midbrain lesions. A group of non-CMD patients was identified with injury to the left thalamus, implicating possible language comprehension difficulties. Shared lesion patterns of globus pallidus and putamen were seen for a group of CMD patients, which have been implicated as part of the anterior forebrain mesocircuit in patients with reversible disorders of consciousness. Thalamocortical network dysfunction was less common in CMD patients [ABCD-index 2.3 (interquartile range, IQR 2.1-3.0) versus 1.4 (IQR 1.0-2.0), P < 0.0001; presence of D 36% versus 3%, P = 0.0006], but WPPC was not different. Bilateral cortical lesions were seen in patients with and without CMD. Thalamocortical disruption did not differ for those with CMD, but long-range WPPC was decreased in 1-4 Hz [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.7-0.9] and increased in 14-30 Hz frequency ranges (OR 1.2; 95% CI 1.0-1.5). These structural and functional data implicate a failure of motor command integration at the anterior forebrain mesocircuit level with preserved thalamocortical network function for CMD patients with subcortical lesions. Amongst patients with bilateral cortical lesions preserved cortico-cortical network function is associated with CMD detection. These data may allow screening for CMD based on widely available structural MRI and resting EEG., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Surgeons and perioperative staff experience high rates of burnout manifesting as exhaustion, depersonalization, and lack of achievement. Consequences include increases in errors and adverse patient events. Little data exist regarding the effectiveness of multidisciplinary peer support systems in combatting burnout. We sought to improve staff morale through establishment of a formally trained, multidisciplinary peer support team., Methods: Selfselected surgeons, anesthesiologists, and nurses were formally trained as Peer Responders as part of an institutional peer support program. All perioperative staff at our pediatric surgery center (n = 120) were surveyed before initiation of the program and then 1-mo and 12-mo after initiation. Primary outcomes were unit morale, unit support, and peer approachability. Kruskal-Wallis tests and Chi-squared tests were used for comparison of primary outcomes among surveys and by position with an alpha value of 0.05 set for significance. Institutional review board approval was waived., Results: The survey response rates were 57.5%, 32.5%, and 37.5% chronologically. After 1 year, there were statistically significant increases in unit support (P < 0.01) and peer approachability (P < 0.001), and a nonstatistically significant increase in unit morale (P = 0.22). On subgroup analysis by staff role, surgeons were least likely to utilize peer support., Conclusions: A multidisciplinary peer support team is an effective and easily reproducible means of building a culture of support and improving morale among perioperative staff. Surgeons were least likely to seek interprofessional peer support. Consequently, surgeon-specific strategies may be necessary. Further investigations are ongoing regarding secondary effects on staff burnout rates, patient safety, and quality of care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: For patients and intimate partners, the challenge of advanced cancer is often compounded by difficulties in effectively communicating about disease treatment. Relevant evidence-based data are limited, in part because of limitations in understanding the dynamics of dyad-based communication., Objectives: This pilot study targeted development/feasibility testing of a practical model for assessment of these dynamics in a small group of cancer patients and their intimate partners, with a focus on communication before/after cancer diagnoses, including end-of-life discussions., Methods: A descriptive phenomenological design was based on the Bodenmann systemic-transactional model of dyadic coping and on semistructured interviews with 7 dyads. Qualitative data analysis used the Colaizzi 7-step method for narrated text interpretation and identification of emergent themes., Results: Patients (median age, 59 years; median intimate partner age, 52 years) had been given a diagnosis of cancer 0 to 6 months before enrollment and were receiving active therapy during participation. Of 534 significant statements analyzed, 2 emergent themes were identified: (1) vulnerable communication during advanced cancer is influenced by preexisting dynamics and complicated by balancing hope/positivity and uncertainty/fear, and (2) communications about end-of-life issues are emotional and influenced by dyad member perceptions about death. A study with a broader racial/demographic representation is planned., Conclusion: It is feasible to study dyad communication in the advanced cancer setting, and preliminary data suggest the importance of these dynamics in expression of clinical preferences., Implications for Practice: Structured interviews with dyads during advanced cancer care can be used to identify specific challenges and inform improved support approaches., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902)., Methods: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines. The ability of ABBV-467 to induce tumor growth inhibition was investigated in xenograft models of human multiple myeloma and acute myelogenous leukemia. The first-in-human study was a multicenter, open-label, dose-escalation study assessing safety, pharmacokinetics, and efficacy of ABBV-467 monotherapy., Results: Here we show that administration of ABBV-467 to MCL-1-dependent tumor cell lines triggers rapid and mechanism-based apoptosis. In vivo, intermittent dosing of ABBV-467 as monotherapy or in combination with venetoclax inhibits the growth of xenografts from human hematologic cancers. Results from a clinical trial evaluating ABBV-467 in patients with multiple myeloma based on these preclinical data indicate that treatment with ABBV-467 can result in disease control (seen in 1 patient), but may also cause increases in cardiac troponin levels in the plasma in some patients (seen in 4 of 8 patients), without other corresponding cardiac findings., Conclusions: The selectivity of ABBV-467 suggests that treatment-induced troponin release is a consequence of MCL-1 inhibition and therefore may represent a class effect of MCL-1 inhibitors in human patients., (© 2023. Springer Nature Limited.)

The Australian Cardiovascular Alliance (ACvA), the Cardiac Society of Australia and New Zealand (CSANZ) and the National Heart Foundation of Australia (NHFA) recently joined forces to bring the cardiovascular and stroke community together to convene and document a national discussion and propose a national CVD Implementation and Policy agenda and action plan. This includes prevention and screening, acute care and secondary prevention., (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Programmes that work with parents to build couple relationship and parenting skills and include critical reflection on gender norms are a promising approach for reducing violence against women and children. However, there is limited evidence of their longer-term impact. In Rwanda, the Bandebereho programme engaged expectant and current parents of children under five years. At 21-months, Bandebereho demonstrated positive impacts on intimate partner violence (IPV), child physical punishment, maternal health-seeking, and couple relations. This study seeks to explore whether those outcomes are sustained six years later., Methods: A six-year follow-up to a two-arm, multi-site randomised controlled trial was conducted in four districts of Rwanda between May and September 2021. At baseline, couples were randomly assigned to either the 15-session intervention (n = 575) or a control group (n = 624). At this follow-up, 1003 men and 1021 women were included in intention to treat analysis. Generalised estimating equations with robust standard errors were used to fit the models. This study was registered with Clinicaltrials.gov (NCT04861870)., Findings: Bandebereho has lasting effects on IPV and physical punishment of children, alongside multiple health and relationship outcomes. Compared to the control group: intervention women report less past-year physical (OR = 0.45, 95% CI 0.34-0.60 p < 0.001), sexual (OR = 0.50, 95% CI 0.37-0.67, p < 0.001), economic (OR = 0.47 95% CI 0.34-0.64, p < 0.001), and moderate or severe emotional (OR = 0.40 95% CI 0.29-0.56, p < 0.001) IPV. Intervention couples report less child physical punishment (OR = 0.72, p = 0.009 for men; OR = 0.68, p = 0.017 for women), fewer depressive symptoms (OR = 0.52, p < 0.001 for men; OR = 0.50, p < 0.001 for women), less harmful alcohol use, and improved maternal health-seeking, father engagement, and division of household labour and decision-making., Interpretation: Our study expands the evidence, demonstrating that programmes engaging men and women to promote collaborative and non-violent couple relations can result in sustained reductions in family violence six years later., Funding: The Echidna Giving Fund, Grand Challenges Canada, the Oak Foundation, and Wellspring Philanthropic Fund supported this study., Competing Interests: Three authors participated in the development of the Bandebereho curriculum (KD, SK, EK). Two authors monitored the implementation of the programme pilot in 2015 assessed in this study (SK, EK); EK was involved in the supervision of data collection of this six-year follow-up but did not directly collect any data. Eight authors’ involvement in the study was funded (salaries or consulting fees) via grants from Echidna Giving Fund, Wellspring Philanthropic, the Oak Foundation, and Grand Challenges Canada to RWAMREC or Equimundo (KD, RGL, DR, SK, GB, EK, FR, SN); three authors were funded to travel to present study findings (KD, EK, FR). Eight authors are currently involved in the scale-up of Bandebereho through the Rwandan health system (KD, EK, SK, FR, FS, SN, GB, HS), including as members of a technical advisory group., (© 2023 The Author(s).)

Clinical laboratory test results alone are of little value in diagnosing, treating, and monitoring health conditions; as such, a clinically actionable cutoff or reference interval is required to provide context for result interpretation. Healthcare practitioners base their diagnoses, follow-up treatments, and subsequent testing on these reference points. However, they may not be aware of inherent limitations related to the definition and derivation of reference intervals. Laboratorians are responsible for providing the reference intervals they report with results. Yet, the establishment and verification of reference intervals using conventional direct methods are complicated by resource constraints or unique patient demographics. To facilitate standardized reference interval best practices, multiple global scientific societies are actively drafting guidelines and seeking funding to promote these initiatives. Numerous national and international multicenter collaborations demonstrate the ability to leverage combined resources to conduct large reference interval studies by direct methods. However, not all demographics are equally accessible. Novel indirect methods are attractive solutions that utilize computational methods to define reference distributions and reference intervals from mixed data sets of pathologic and non-pathologic patient test results. In an effort to make reference intervals more accurate and personalized, individual-based reference intervals are shown to be more useful than population-based reference intervals in detecting clinically significant analyte changes in a patient that might otherwise go unrecognized when using wider, population-based reference intervals. Additionally, continuous reference intervals can provide more accurate ranges as compared to age-based partitions for individuals that are near the ends of the age partition. The advantages and disadvantages of different reference interval approaches as well as the advancement of non-conventional reference interval studies are discussed in this review.

Most impact evaluations of intimate partner violence (IPV) prevention interventions use binary measures of "any" versus "no" physical and/or sexual IPV as their primary outcome measure, missing opportunities to capture nuance. In this study, we reanalyzed secondary data from six randomized controlled trials conducted in low- and middle-income countries-Bandebereho (Rwanda), Becoming One (Uganda), Indashyikirwa (Rwanda), MAISHA CRT01, MAISHA CRT02 (Tanzania), Stepping Stones Creating Futures (South Africa), and Unite for a Better Life (Ethiopia), to assess how different conceptualizations and coding of IPV variables can influence interpretations of the impact of an intervention. We compared the standard outcome measures to new measures that reflect the severity and intensity of violence and whether interventions prevent new cases of IPV or reduce or stop ongoing violence. Results indicate that traditional binary indicators masked some of the more subtle intervention effects, and the use of the new indicators allowed for a better understanding of the impacts of the interventions. Conclusions on whether a program is perceived "to work" are highly influenced by the IPV outcomes that the investigators choose to report, and how they are measured and coded. Lack of attention to outcome choice and measurement could lead to prematurely abandoning strategies useful for violence reduction or missing essential insights into how programs may or may not affect IPV. While these results must be interpreted cautiously, given differences in intervention types, the underlying prevalence of violence, sociodemographic factors, sample sizes, and other contextual differences across the trial sites, they can help us move toward a new approach to reporting multiple outcomes that allow us to unpack the "impact" of an intervention by assessing intervention effect by the severity of violence and type of prevention, whether primary and secondary.

Background: Machine perfusion (MP) is increasingly used for human transplant organ preservation. The use of MP for research purposes is another opportunity for this technology. The porcine pancreas and liver are similar in anatomical size and function to their human counterparts, making them an excellent resource for research, but they have some important differences from human organs which can influence their research use. In this paper, we describe a technique developed and tested for the retrieval of porcine organs for use in research on perfused viable organs., Methods: Whole-organ porcine pancreata and livers were harvested at a commercial abattoir, following standard slaughterhouse processes. The standard slaughterhouse process involved a thoracotomy and mid-line laparotomy, and all the thoracoabdominal organs were removed. The pancreas, fixed in the retroperitoneum, was carefully dissected from its attachments to the surrounding structures, and tissue planes between the pancreas, spleen, duodenum, and colon were meticulously identified and dissected. Vessel exposure and division: The aorta, portal vein (PV), hepatic vein (HV), and hepatic artery (HA) were dissected and isolated, preserving the input and output channels for the liver and pancreas. A distal 3 cm of the aorta was preserved and divided and served as the input for the pancreas perfusions. The liver, PV, HV, and HA were preserved and divided to preserve the physiological channels of the input (PV and HA) and output (HV) for the liver perfusions. The porcine hepatic and pancreas anatomy shares significant resemblance with the gross anatomy found in humans, and this was taken into consideration when designing the perfusion circuitry. The porcine pancreas and spleen shared a common blood supply, with branches arising from the splenic artery. The organs were flushed with cold, heparinised normal saline and transported in a temperature-regulated receptacle maintained at a core temperature between 4 and 8 °C, in line with the standards of static cold storage (SCS), to a dedicated perfusion lab and perfused using our novel perfusion machine with autologous, heparinised porcine blood, also collected at the abattoir.

The Australian rainforest is a rich source of medicinal plants that have evolved in the face of dramatic environmental challenges over a million years due to its prolonged geographical isolation from other continents. The rainforest consists of an inherent richness of plant secondary metabolites that are the most intense in the rainforest. The search for more potent and more bioavailable compounds from other plant sources is ongoing, and our short review will outline the pathways from the discovery of bioactive plants to the structural identification of active compounds, testing for potency, and then neuroprotection in a triculture system, and finally, the validation in an appropriate neuro-inflammatory mouse model, using some examples from our current research. We will focus on neuroinflammation as a potential treatment target for neurodegenerative diseases including multiple sclerosis (MS), Parkinson's (PD), and Alzheimer's disease (AD) for these plant-derived, anti-inflammatory molecules and highlight cytokine suppressive anti-inflammatory drugs (CSAIDs) as a better alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) to treat neuroinflammatory disorders.

Optical imaging techniques such as spectral imaging show promise for the assessment of tissue health during surgery; however, the validation and translation of such techniques into clinical practise is limited by the lack of representative tissue models. In this paper, we demonstrate the application of an organ perfusion machine as an ex vivo tissue model for optical imaging. Three porcine livers are perfused at stepped blood oxygen saturations. Over the duration of each perfusion, spectral data of the tissue are captured via diffuse optical spectroscopy and multispectral imaging. These data are synchronised with blood oxygen saturation measurements recorded by the perfusion machine. Shifts in the optical properties of the tissue are demonstrated over the duration of the each perfusion, as the tissue becomes reperfused and as the oxygen saturation is varied.

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa., Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation., Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa., Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement., Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Little is known about the natural history of comatose patients with brain injury, as in many countries most of these patients die in the context of withdrawal of life-sustaining therapies (WLSTs). The accuracy of predicting recovery that is used to guide goals-of-care decisions is uncertain. We examined long-term outcomes of patients with ischemic or hemorrhagic stroke predicted by experienced clinicians to have no chance of meaningful recovery in Japan, where WLST in patients with isolated neurological disease is uncommon., Methods: We retrospectively reviewed the medical records of all patients admitted with acute ischemic stroke, intracerebral hemorrhage, or nontraumatic subarachnoid hemorrhage between January 2018 and December 2020 to a neurocritical care unit at Toda Medical Group Asaka Medical Center in Saitama, Japan. We screened for patients who were predicted by the attending physician on postinjury day 1-4 to have no chance of meaningful recovery. Primary outcome measures were disposition at hospital discharge and the ability to follow commands and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E), which was assessed 6 months after injury., Results: From 860 screened patients, we identified 40 patients (14 with acute ischemic stroke, 19 with intracerebral hemorrhage, and 7 with subarachnoid hemorrhage) who were predicted to have no chance of meaningful recovery. Median age was 77 years (interquartile range 64-85), 53% (n = 21) were women, and 80% (n = 32) had no functional deficits prior to hospitalization. Six months after injury, 17 patients were dead, 14 lived in a long-term care hospital, 3 lived at home, 2 lived in a rehabilitation center, and 2 lived in a nursing home. Three patients reliably followed commands, two were in a vegetative state (GOS-E 2), four fully depended on others and required constant assistance (GOS-E 3), one could be left alone independently for 8 h per day but remained dependent (GOS-E 4), and one was independent and able to return to work-like activities (GOS-E 5)., Conclusions: In the absence of WLST, almost half of the patients predicted shortly after the injury to have no chance of meaningful recovery were dead 6 months after the injury. A small minority of patients had good functional recovery, highlighting the need for more accurate neurological prognostication., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: This paper presents an assessment of a low-cost organ perfusion machine designed for use in research settings. The machine is modular and versatile in nature, built on a robotic operating system (ROS2) pipeline allowing for the addition of specific sensors for different research applications. Here we present the system and the development stages to achieve viability of the perfused organ., Methods: The machine's perfusion efficacy was assessed by monitoring the distribution of perfusate in livers using methylene blue dye. Functionality was evaluated by measuring bile production after 90 min of normothermic perfusion, while viability was examined using aspartate transaminase assays to monitor cell damage throughout the perfusion. Additionally, the output of the pressure, flow, temperature, and oxygen sensors was monitored and recorded to track the health of the organ during perfusion and assess the system's capability of maintaining the quality of data over time., Results: The results show the system is capable of successfully perfusing porcine livers for up to three hours. Functionality and viability assessments show no deterioration of liver cells once normothermic perfusion had occurred and bile production was within normal limits of approximately 26 ml in 90 min showing viability., Conclusion: The developed low-cost perfusion system presented here has been shown to keep porcine livers viable and functional ex vivo. Additionally, the system is capable of easily incorporating several sensors into its framework and simultaneously monitor and record them during perfusion. The work promotes further exploration of the system in different research domains., (© 2023. The Author(s).)

Background: Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological tissues in real time but has not been used in thrombus., Objective: To perform a feasibility study of EIS analysis of thrombi retrieved by MT to evaluate: (1) the ability of EIS and machine learning to predict red blood cell (RBC) percentage content of thrombi and (2) to classify the thrombi as "RBC-rich" or "RBC-poor" based on a range of cutoff values of RBC., Methods: ClotbasePilot was a multicentric, international, prospective feasibility study. Retrieved thrombi underwent histological analysis to identify proportions of RBC and other components. EIS results were analyzed with machine learning. Linear regression was used to evaluate the correlation between the histology and EIS. Sensitivity and specificity of the model to classify the thrombus as RBC-rich or RBC-poor were also evaluated., Results: Among 514 MT,179 thrombi were included for EIS and histological analysis. The mean composition in RBC of the thrombi was 36% ± 24. Good correlation between the impedance-based prediction and histology was achieved (slope of 0.9, R 2   =  0.53, Pearson coefficient  =  0.72). Depending on the chosen cutoff, ranging from 20 to 60% of RBC, the calculated sensitivity for classification of thrombi ranged from 77 to 85% and the specificity from 72 to 88%., Conclusion: Combination of EIS and machine learning can reliably predict the RBC composition of retrieved ex vivo AIS thrombi and then classify them into groups according to their RBC composition with good sensitivity and specificity.

Introduction: We aimed to assess the validity and reproducibility of a wearable hydration device in a cohort of maintenance dialysis patients., Methods: We conducted a prospective, single-arm observational study on 20 haemodialysis patients between January and June 2021 in a single centre. A prototype wearable infrared spectroscopy device, termed the Sixty device, was worn on the forearm during dialysis sessions and nocturnally. Bioimpedance measurements were performed 4 times using the body composition monitor (BCM) over 3 weeks. Measurements from the Sixty device were compared with the BCM overhydration index (litres) pre- and post-dialysis and with standard haemodialysis parameters., Results: 12 out of 20 patients had useable data. Mean age was 52 ± 12.4 years. The overall accuracy for predicting pre-dialysis categories of fluid status using Sixty device was 0.55 [K = 0.00; 95% CI: -0.39-0.42]. The accuracy for the prediction of post-dialysis categories of volume status was low [accuracy = 0.34, K = 0.08; 95% CI: -0.13-0.3]. Sixty outputs at the start and end of dialysis were weakly correlated with pre- and post-dialysis weights ( r = 0.27 and r = 0.27, respectively), as well as weight loss during dialysis ( r = 0.31), but not ultrafiltration volume ( r = 0.12). There was no difference between the change in Sixty readings overnight and the change in Sixty readings during dialysis (mean difference 0.09 ± 1.5 kg), [ t (39) = 0.38, p = 0.71]., Conclusion: A prototype wearable infrared spectroscopy device was unable to accurately assess changes in fluid status during or between dialysis sessions. In the future, hardware development and advances in photonics may enable the tracking of interdialytic fluid status., Competing Interests: Vicki Sandys, Lavleen Bhat, Anna Ninan, and Shane Kelly have no financial interests or COI to declare. Conall O’Seaghdha and Donal Sexton are shareholders in patientMpower. Colin Edwards is an employee, director, and shareholder in patientMpower. Paul McAleese is the founder and CEO of Design to Value Ltd. Emer O’Hare has shares in ResMed and Novartis. Conall O’Seaghdha, Vicki Sandys, Lavleen Bhat, and Emer O’Hare have a patient application pending “System and method for predicting dry weight of a haemodialysis patient.” Patent application number 2208945.2 United Kingdom Intellectual Property Office., (© 2023 The Author(s). Published by S. Karger AG, Basel.)