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Children and adolescents (henceforth "children") with both attention-deficit/hyperactivity disorder (ADHD) and anxiety experience greater difficulties than children with either alone, though qualitative methodologies are yet to be used to understand the challenges this population experiences. We aimed to explore parent-reported daily impacts of co-occurring anxiety in children with ADHD (ages 8-13 years). Participants were enrolled in an Australian trial evaluating an adapted anxiety intervention and were eligible if their child met diagnostic criteria for ADHD plus separation, social, and/or generalized anxiety disorder. A baseline measure of life impacts associated with child anxiety captured situations parents reported were difficult, due to their child's anxiety. Reflexive thematic analysis of free-text responses (N = 203) facilitated new insights via inductively generating key themes. Three overarching themes highlighted (1) child difficulties with everyday situations and processes due to their anxiety; (2) the nature of the child's anxiety being pervasive and unrelenting; and (3) the strain placed on the child's family system. This study enhances understanding of daily impacts associated with co-occurring anxiety and ADHD and may contribute to an improved understanding of support needs. Results reiterate the need to identify co-occurring difficulties in children with ADHD and support both children and their families.

Although well established in developed countries, Ethics review boards in the academia, and specifically for social and behavioral sciences (SBS) research, is a relatively new, and still a controversy inducing endeavor. This study explores the establishment and functioning of ERBs in Israeli academia, serving as a case study for the challenges and progress made in ensuring ethical research practices in non-medical related spheres. A purposeful sample of 46 participants was selected, comprising ERB current or past members and SBS researchers, who each interacted extensively with ERB's evaluation processes. The participants came from all eight research universities of Israel, as well as seven large public and private academic colleges. Open, semi structured In-depth interviews were conducted in order to facilitate a critical reflective stance among the various participants, exploring their experiences, behaviors and the meanings they assign to ERB processes. Our research revealed two major themes. The first is the developmental trajectories in the construction processes of ERBs in Israel, comprised of the following stages: Initiation, expansion, opposition, and acceptance and assimilation. The second was a typology of participation throughout the ERBs' construction process. Inspired by Merton's strain theory, this typology includes conformists, ritualists, ideologists, control-freaks, and insurgents. The findings expose a unique perspective into the initiation, establishment, and development of ERBs, which can shed light on the role of ERBs in general, as well as point out how resistance to ERBs, as well as the different reasons for championing them, affected not only ERBs form and their legitimacy, but also their interaction with researchers.

Abstract Background Severe trauma is associated with systemic inflammation and organ dysfunction. Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma. The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury. Methods Male Sprague–Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock (LCHS), multicompartmental polytrauma (PT) (unilateral lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), or naïve controls. Weight, plasma toll‐like receptor 4 (TLR4), hemoglobin, spleen to body weight ratio, bone marrow (BM) erythroid progenitor (CFU‐GEMM, BFU‐E, and CFU‐E) growth, plasma granulocyte colony‐stimulating factor (G‐CSF) and right lung histologic injury were assessed on day 7, with significance defined as p values

BackgroundWhile sepsis, an exaggerated response to infection, can affect people of all age groups, it is more prevalent in middle-aged and older adults. Older adults suffer worse short-term and long-term outcomes than younger patients. Older sepsis survivors are commonly discharged to long-term acute care facilities, where they often die within 1 year. Those who return home from the hospital lose the momentum of physical function improvement after early inpatient rehabilitation, and often face exacerbation of comorbidities and decline in physical function. Additionally, patients who are discharged home often live at distant locations and are not able to commute to rehabilitation centers due to their poor health status. Therefore, remotely delivered exercise interventions tailored to this population hold promise to improve physical function safely and effectively after sepsis. However, this type of intervention has yet to be tested in this population. ObjectiveThis study aims to assess the safety, feasibility, and ease of recruitment and retention of participants for a remotely delivered physical activity intervention for improving physical function in middle-aged and older sepsis survivors. MethodsThe proposed intervention will be delivered through a digital health platform that comprises a patient-facing mobile app and a 12-week physical activity program specifically designed for middle-aged and older sepsis survivors with poor health status who may face challenges participating in traditional out-patient or community-based exercise interventions. This study is ongoing and plans to enroll 40 sepsis survivors aged 55 years and older who will be randomized to either a remotely delivered exercise intervention group or a control group (electronic health diary). Both groups will use a tablet containing the Health in Motion app (Blue Marble Health). The intervention group will receive a clinician-designed personalized avatar-guided home exercise program and reminders while the control group will self-report daily activities using the in-app health diary feature. ResultsThis study is the first to use a home-based, remotely monitored 12-week exercise program to improve physical function in sepsis survivors. This study will evaluate the safety, feasibility, and efficacy, providing the necessary knowledge to design and calculate power for future larger trials. ConclusionsThis study will provide important information for planning a future randomized clinical trial to test the efficacy of a remotely delivered exercise intervention in this high-risk population. Trial RegistrationClinicalTrials.gov NCT05568511; https://clinicaltrials.gov/study/NCT05568511 International Registered Report Identifier (IRRID)DERR1-10.2196/60270

IntroductionSepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.MethodsThis prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an ‘immunocompetent’, ‘immunosuppressed endotype’, and two ‘mixed’ endotypes.ResultsWhole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. ‘Immunocompetent’ endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the ‘immunosuppressed’ endotype. Similarly, ‘immunocompetent’ endotype patients on day 4 had a higher in-hospital survival compared to the ‘immunosuppressed’ endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality.ConclusionsIncreased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early ‘immunocompetent’ endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.

Objective: To investigate the longitudinal associations between COVID-19 induced stress (related to COVID-19 restrictions/changes), attention-deficit/hyperactivity disorder (ADHD) symptoms, oppositional symptoms, and mental health outcomes (negative affect, anxiety, depression, and irritability) in children with ADHD during the COVID-19 pandemic. Method: Parents of 140 Australian children with ADHD (aged 5-17 years) completed an online survey in May 2020 during stay-at-home restrictions and 12-months later. Results: Baseline COVID-19 stress was associated with increased total ADHD symptom severity ([beta] = 0.21, p = 0.007) and hyperactivity/impulsivity symptoms ([beta] = 0.23, p = 0.002) at 12-months, after accounting for covariates (i.e., child age, gender, ADHD medication, socio-economic status, and baseline symptoms). Despite some indication of associations between baseline COVID-19 stress and 12-month oppositional symptoms and negative affect, these were attenuated when adjusting for baseline symptoms. Conclusions: The study provides initial evidence of the medium-term impacts of pandemic-related stress for children with ADHD.

Crop disease management is crucial for sustainable food production. Although farmers in Nigeria continue to apply broad-spectrum fungicides to potato, potato diseases are still on the rise. Machine-learning methods have recently become more common as part of epidemiological early warning systems. They provide vital information on data–disease relations that may be useful for predisease management. In this study, we build on machine-learning methods to develop spatial early warning tools for Nigeria, using the Jos Plateau as a test case. Both remote sensing meteorological and field data were used to (i) predict disease incidence using field reference data and a random forest (RF) classifier and to (ii) identify local conditions conducive to potato diseases using multi-criteria classification (MCC) based on machine-learning results. The results of the RF for 2019, 2020, and 2021 showed similar spatial characteristics, whereas the MCC varied significantly. Both models predicted that between 72 and 96% of potato fields would be infested. The MCC model further revealed that spatiotemporal frequencies of vulnerability in June can serve as the indicator that informs degrees of infestation. A 5-day vulnerability window used in the context of the MCC proved to be the most useful tool for developing an efficient spraying regime, based on a combination of temperature, rainfall, and relative humidity thresholds. As a result, we were able to develop an operational early-warning system for potato disease in the tropical highlands of Africa. In particular, we introduced spatial risks, creating a more sustainable early-warning approach. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Background: Total neoadjuvant therapy (TNT) is an accepted approach for the management of locally advanced rectal cancer (LARC) and is associated with a decreased risk of development of metastatic disease compared to standard neoadjuvant therapy. However, questions remain regarding surgical outcomes and local control in patients who proceed to surgery, particularly when radiation is given first in the neoadjuvant sequence. We report on our institution's experience with patients who underwent short-course radiation therapy, consolidation chemotherapy, and surgery. Methods: We retrospectively reviewed surgical specimen outcomes, postoperative complications, and local/pelvic control in a large cohort of patients with LARC who underwent neoadjuvant therapy incorporating upfront short-course radiation therapy followed by consolidation chemotherapy. Results: In our cohort of 83 patients who proceeded to surgery, a complete/near-complete mesorectal specimen was achieved in 90 % of patients. This outcome was not associated with the time interval from completion of radiation to surgery. Postoperative complications were acceptably low. Local control at two years was 93.4 % for all patients- 97.6 % for those with low-risk disease and 90.4 % for high-risk disease. Conclusion: Upfront short-course radiation therapy and consolidation chemotherapy is an effective treatment course. Extended interval from completion of short-course radiation therapy did not impact surgical specimen quality.

Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52–61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16–36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.

ABSTRACTAlzheimer’s disease (AD) is a debilitating brain disorder with rapidly mounting prevalence worldwide, yet no proven AD cure has been discovered. Using a multi-omics approach in a transgenic AD mouse model, the current study demonstrated the efficacy of a modified Mediterranean-ketogenic diet (MkD) on AD-related neurocognitive pathophysiology and underlying mechanisms related to the gut-microbiome-brain axis. The findings revealed that MkD induces profound shifts in the gut microbiome community and microbial metabolites. Most notably, MkD promoted growth of the Lactobacillus population, resulting in increased bacteria-derived lactate production. We discovered elevated levels of microbiome- and diet-derived metabolites in the serum as well, signaling their influence on the brain. Importantly, these changes in serum metabolites upregulated specific receptors that have neuroprotective effects and induced alternations in neuroinflammatory-associated pathway profiles in hippocampus. Additionally, these metabolites displayed strong favorable co-regulation relationship with gut-brain integrity and inflammatory markers, as well as neurobehavioral outcomes. The findings underscore the ameliorative effects of MkD on AD-related neurological function and the underlying gut-brain communication via modulation of the gut microbiome-metabolome arrays.

The degree to which artificial intelligence healthcare research is informed by data and stakeholders from community settings has not been previously described. As communities are the principal location of healthcare delivery, engaging them could represent an important opportunity to improve scientific quality. This scoping review systematically maps what is known and unknown about community-engaged artificial intelligence research and identifies opportunities to optimize the generalizability of these applications through involvement of community stakeholders and data throughout model development, validation, and implementation. Embase, PubMed, and MEDLINE databases were searched for articles describing artificial intelligence or machine learning healthcare applications with community involvement in model development, validation, or implementation. Model architecture and performance, the nature of community engagement, and barriers or facilitators to community engagement were reported according to PRISMA extension for Scoping Reviews guidelines. Of approximately 10,880 articles describing artificial intelligence healthcare applications, 21 (0.2%) described community involvement. All articles derived data from community settings, most commonly by leveraging existing datasets and sources that included community subjects, and often bolstered by internet-based data acquisition and subject recruitment. Only one article described inclusion of community stakeholders in designing an application-a natural language processing model that detected cases of likely child abuse with 90% accuracy using harmonized electronic health record notes from both hospital and community practice settings. The primary barrier to including community-derived data was small sample sizes, which may have affected 11 of the 21 studies (53%), introducing substantial risk for overfitting that threatens generalizability. Community engagement in artificial intelligence healthcare application development, validation, or implementation is rare. As healthcare delivery occurs primarily in community settings, investigators should consider engaging community stakeholders in user-centered design, usability, and clinical implementation studies to optimize generalizability.

CONTEXT:. Sepsis leads to multiple organ dysfunction and negatively impacts patient outcomes. Skeletal muscle disuse is a significant comorbidity in septic patients during their ICU stay due to prolonged immobilization. HYPOTHESIS:. Combination of sepsis and muscle disuse will promote a unique proteomic signature in skeletal muscle in comparison to disuse and sepsis separately. METHODS AND MODELS:. Following cecal ligation and puncture (CLP) or Sham surgeries, mice were subjected to hindlimb suspension (HLS) or maintained normal ambulation (NA). Tibialis anterior muscles from 24 C57BL6/J male mice were harvested for proteomic analysis. Proteomic profiles were assessed using nano-liquid chromatography with tandem mass spectrometry, followed by data analysis including Partial Least Squares Discriminant Analysis (PLS-DA), to compare the differential protein expression across groups. RESULTS:. A total of 2876 differentially expressed proteins were identified, with marked differences between groups. In mice subjected to CLP and HLS combined, there was a distinctive proteomic signature characterized by a significant decrease in the expression of proteins involved in mitochondrial function and muscle metabolism, alongside a marked increase in proteins related to muscle degradation pathways. The PLS-DA demonstrated a clear separation among experimental groups, highlighting the unique profile of the CLP/HLS group. This suggests an important interaction between sepsis-induced inflammation and disuse atrophy mechanisms in sepsis-induced myopathy. INTERPRETATIONS AND CONCLUSIONS:. Our findings reveal a complex proteomic landscape in skeletal muscle exposed to sepsis and disuse, consistent with an exacerbation of muscle protein degradation under these combined stressors. The identified proteins and their roles in cellular stress responses and muscle pathology provide potential targets for intervention to mitigate muscle dysfunction in septic conditions, highlighting the importance of addressing both sepsis and disuse concurrently in clinical and experimental settings.

Background:. Surrogates, proxies, and clinicians making shared treatment decisions for patients who have lost decision-making capacity often fail to honor patients’ wishes, due to stress, time pressures, misunderstanding patient values, and projecting personal biases. Advance directives intend to align care with patient values but are limited by low completion rates and application to only a subset of medical decisions. Here, we investigate the potential of large language models (LLMs) to incorporate patient values in supporting critical care clinical decision-making for incapacitated patients in a proof-of-concept study. Methods:. We simulated text-based scenarios for 50 decisionally incapacitated patients for whom a medical condition required imminent clinical decisions regarding specific interventions. For each patient, we also simulated five unique value profiles captured using alternative formats: numeric ranking questionnaires, text-based questionnaires, and free-text narratives. We used pre-trained generative LLMs for two tasks: 1) text extraction of the treatments under consideration and 2) prompt-based question-answering to generate a recommendation in response to the scenario information, extracted treatment, and patient value profiles. Model outputs were compared with adjudications by three domain experts who independently evaluated each scenario and decision. Results and Conclusions:. Automated extractions of the treatment in question were accurate for 88% (n = 44/50) of scenarios. LLM treatment recommendations received an average Likert score by the adjudicators of 3.92 of 5.00 (five being best) across all patients for being medically plausible and reasonable treatment recommendations, and 3.58 of 5.00 for reflecting the documented values of the patient. Scores were highest when patient values were captured as short, unstructured, and free-text narratives based on simulated patient profiles. This proof-of-concept study demonstrates the potential for LLMs to function as support tools for surrogates, proxies, and clinicians aiming to honor the wishes and values of decisionally incapacitated patients.

Academic Medical Centers (AMCs) and Federally Qualified Health Centers (FQHCs) are similarly tasked with managing the health of their local community, yet they each face unique challenges in their ability to do so. Integrating AMCs and FQHCs into novel care delivery models can leverage both organizations strengths, providing care in a comprehensive and sustainable fashion. Johns Hopkins Medicine (JHM) implemented this model with a large East Baltimore medical center, creating an AMC-FQHC collaboration focused on providing care to the East Baltimore patient population. This system provided various improvements in care delivery, including increased staffing, new wraparound services, improved access to funding dollars, and decreased out of pocket costs for patients qualifying for financial assistance. The academic missions of research and training were preserved, serving as the primary continuity clinic for several residency programs and as a community site for research. These changes resulted in more robust care for patients while improving the financial standing of the clinic. Through AMC and FQHC partnership, progress can be made toward providing holistic and financially sustainable primary care services in underserved areas while preserving the tripartite mission of academic medicine, with significant pedagogical and research opportunities.

Objective:. To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts. Background:. In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally. Methods:. This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774). K-means clustering identified sociodemographic phenotypes within overtriage and undertriage cohorts. Results:. Compared with controls, overtriaged admissions had a predominance of male patients (56.2% vs 43.1%, P < 0.001) and commercial insurance (6.4% vs 2.5%, P < 0.001); undertriaged admissions had a predominance of Black patients (28.4% vs 24.4%, P < 0.001) and greater socioeconomic deprivation. Overtriage was associated with increased total direct costs [$16.2K ($11.4K–$23.5K) vs $14.1K ($9.1K–$20.7K), P < 0.001] and low value of care; undertriage was associated with increased hospital mortality (1.5% vs 0.7%, P = 0.002) and hospice care (2.2% vs 0.6%, P < 0.001) and low value of care. Unique sociodemographic phenotypes within both overtriage and undertriage cohorts had similar outcomes and value of care, suggesting that triage decisions, rather than patient characteristics, drive outcomes and value of care. Conclusions:. Postoperative triage decisions should ensure equality across sociodemographic groups by anchoring triage decisions to objective patient acuity assessments, circumventing cognitive shortcuts and mitigating bias.

Background: The aim of this study was to investigate the demographic, clinical characteristics, and service systems of patients with autism spectrum disorder (ASD) and/or intellectual disability presenting to a large paediatric hospital emergency department (ED) with behaviours of concern (BOC) over a two-year period. Method: Retrospective audit of ED presentations with BOC in patients with ASD and/or intellectual disability from 1 January 2019 to 31 December 2020, at the Royal Children's Hospital, Melbourne, Australia. Results: There were 124 presentations (84 patients) in 2019 and 129 presentations (82 patients) in 2020. The mean age was 11.7 years. 55% arrived by ambulance, 24% required physical restraint, and 26% required sedation. Re-presentation was predicted by single-parent household, child protection involvement, and requirement of an interpreter. Conclusions: Children and adolescents with ASD and/or intellectual disability regularly present to ED with BOC. New models of care are required to better support this highly vulnerable patient group.

Recent reforms to Foreign Language Activities policies in Japan have highlighted the importance of facilitating multilingualism and multiculturalism in global contexts. However, many of the most recent elementary school textbooks (2018-2020) for Foreign Language Activities classes in Japan are English Foreign Language (EFL) textbooks focused largely on English language in tourism settings rather than in educational and social perspectives. With inspiration from critical discourse analysis (e.g., Fairclough 1992a; 1992b; 2001), this paper critically examines representations of multilingualism and multiculturalism in four Japanese EFL textbooks used in elementary schools, "We Can 1," "We Can 2," "Let's Try 1" and "Let's Try 2" (MEXT, 2018). Findings show that the videos, video activities, and images center Japanese culture, and that countries outside of Japan appear in over-simplified mediums, while minority cultures within Japan are not explicitly represented.

IntroductionSepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness.MethodsCellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering.ResultsWe identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome.DiscussionThe origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.

RationaleSepsis is a life-threatening, dysregulated response to infection. Lipid biomarkers including cholesterol are dynamically regulated during sepsis and predict short-term outcomes. In this study, we investigated the predictive ability of lipid biomarkers for physical function and long-term mortality after sepsis.MethodsProspective cohort study of sepsis patients admitted to a surgical intensive-care unit (ICU) within 24 h of sepsis bundle initiation. Samples were obtained at enrollment for lipid biomarkers. Multivariate regression models determined independent risk factors predictive of poor performance status (Zubrod score of 3/4/5) or survival at 1-year follow-up.Measurements and main resultsThe study included 104 patients with surgical sepsis. Enrollment total cholesterol and high-density lipoprotein (HDL-C) levels were lower, and myeloperoxidase (MPO) levels were higher for patients with poor performance status at 1 year. A similar trend was seen in comparisons based on 1-year mortality, with HDL-C and ApoA-I levels being lower and MPO levels being higher in non-survivors. However, multivariable logistic regression only identified baseline Zubrod and initial SOFA score as significant independent predictors of poor performance status at 1 year. Multivariable Cox regression modeling for 1-year survival identified high Charlson comorbidity score, low ApoA-I levels, and longer vasopressor duration as predictors of mortality over 1-year post-sepsis.ConclusionsIn this surgical sepsis study, lipoproteins were not found to predict poor performance status at 1 year. ApoA-I levels, Charlson comorbidity scores, and duration of vasopressor use predicted 1 year survival. These data implicate cholesterol and lipoproteins as contributors to the underlying pathobiology of sepsis.

Abstract Introduction The evolution of pre- versus postoperative risk factors remains unknown in the development of persistent postoperative pain and opioid use. We identified preoperative versus comprehensive perioperative models of delayed pain and opioid cessation after total joint arthroplasty including time-varying postoperative changes in emotional distress. We hypothesized that time-varying longitudinal measures of postoperative psychological distress, as well as pre- and postoperative use of opioids would be the most significant risk factors for both outcomes. Methods A prospective cohort of 188 patients undergoing total hip or knee arthroplasty at Stanford Hospital completed baseline pain, opioid use, and emotional distress assessments. After surgery, a modified Brief Pain Inventory was assessed daily for 3 months, weekly thereafter up to 6 months, and monthly thereafter up to 1 year. Emotional distress and pain catastrophizing were assessed weekly to 6 months, then monthly thereafter. Stepwise multivariate time-varying Cox regression modeled preoperative variables alone, followed by all perioperative variables (before and after surgery) with time to postoperative opioid and pain cessation. Results The median time to opioid and pain cessation was 54 and 152 days, respectively. Preoperative total daily oral morphine equivalent use (hazard ratio-HR 0.97; 95% confidence interval-CI 0.96–0.98) was significantly associated with delayed postoperative opioid cessation in the perioperative model. In contrast, time-varying postoperative factors: elevated PROMIS (Patient-Reported Outcomes Measurement Information System) depression scores (HR 0.92; 95% CI 0.87–0.98), and higher Pain Catastrophizing Scale scores (HR 0.85; 95% CI 0.75–0.97) were independently associated with delayed postoperative pain resolution in the perioperative model. Conclusions These findings highlight preoperative opioid use as a key determinant of delayed postoperative opioid cessation, while postoperative elevations in depressive symptoms and pain catastrophizing are associated with persistent pain after total joint arthroplasty providing the rationale for continued risk stratification before and after surgery to identify patients at highest risk for these distinct outcomes. Interventions targeting these perioperative risk factors may prevent prolonged postoperative pain and opioid use.

Abstract Background Sepsis is a heterogenous syndrome with limited therapeutic options. Identifying immunological endotypes through gene expression patterns in septic patients may lead to targeted interventions. We investigated whether patients admitted to a surgical intensive care unit (ICU) with sepsis and with high risk of mortality express similar endotypes to non-septic, but still critically ill patients using two multiplex transcriptomic metrics obtained both on admission to a surgical ICU and at set intervals. Methods We analyzed transcriptomic data from 522 patients in two single-site, prospective, observational cohorts admitted to surgical ICUs over a 5-year period ending in July 2020. Using an FDA-cleared analytical platform (nCounter FLEX®, NanoString, Inc.), we assessed a previously validated 29-messenger RNA transcriptomic classifier for likelihood of 30-day mortality (IMX-SEV-3) and a 33-messenger RNA transcriptomic endotype classifier. Clinical outcomes included all-cause mortality, development of chronic critical illness, and secondary infections. Univariate and multivariate analyses were performed to assess for true effect and confounding. Results Sepsis was associated with a significantly higher predicted and actual hospital mortality. At enrollment, the predominant endotype for both septic and non-septic patients was adaptive, though with significantly different distributions. Inflammopathic and coagulopathic septic patients, as well as inflammopathic non-septic patients, showed significantly higher frequencies of secondary infections compared to those with adaptive endotypes (p

ABSTRACTInvasive meningococcal disease (IMD) is a life-threatening disease caused by meningococcal serogroups A, B, C, W, X, and Y, of which B and W are most common in Argentina. The 4-component meningococcal serogroup B (4CMenB) vaccine contains three purified recombinant protein antigens (Neisseria adhesin A [NadA], factor H binding protein [fHbp], and Neisserial Heparin Binding Antigen [NHBA]) and outer membrane vesicles (OMV), which is derived from the New Zealand epidemic strain and contains Porin A 1.4. These antigens are present and conserved in strains that belong to other serogroups. In this study, we show that 10/11 (91%) meningococcal serogroup W (MenW) strains selected to be representative of MenW isolates that caused IMD in Argentina during 2010–2011 were killed in bactericidal assays by the sera of adolescents and infants who had been immunized with the 4CMenB vaccine. We also show that MenW strains that caused IMD in Argentina during 2018–2021 were genetically similar to the earlier strains, indicating that the 4CMenB vaccine would likely still provide protection against current MenW strains. These data highlight the potential of 4CMenB vaccination to protect adolescents and infants against MenW strains that are endemic in Argentina.

Abstract Background Outcomes following aortic occlusion for trauma and hemorrhagic shock are poor, leading some to question the clinical utility of aortic occlusion in this setting. This study evaluates neurologically intact survival following resuscitative endovascular balloon occlusion of the aorta (REBOA) versus resuscitative thoracotomy at a center with a dedicated trauma hybrid operating room with angiographic capabilities. Methods This retrospective cohort analysis compared patients who underwent zone 1 aortic occlusion via resuscitative thoracotomy (n = 13) versus REBOA (n = 13) for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock (systolic blood pressure less than 90 mmHg despite volume resuscitation) at a level 1 trauma center with a dedicated trauma hybrid operating room. The primary outcome was survival to hospital discharge. The secondary outcome was neurologic status at hospital discharge, assessed by Glasgow Coma Scale (GCS) scores. Results Overall median age was 40 years, 27% had penetrating injuries, and 23% had pre-hospital closed-chest cardiopulmonary resuscitation. In both cohorts, median injury severity scores and head-abbreviated injury scores were 26 and 2, respectively. The resuscitative thoracotomy cohort had lower systolic blood pressure on arrival (0 [0–75] vs. 76 [65–99], p = 0.009). Hemorrhage control (systolic blood pressure 100 mmHg without ongoing vasopressor or transfusion requirements) was obtained in 77% of all REBOA cases and 8% of all resuscitative thoracotomy cases (p = 0.001). Survival to hospital discharge was greater in the REBOA cohort (54% vs. 8%, p = 0.030), as was discharge with GCS 15 (46% vs. 0%, p = 0.015). Conclusions Among patients undergoing aortic occlusion for blunt or non-thoracic, penetrating trauma and refractory hemorrhagic shock at a center with a dedicated, trauma hybrid operating room, nearly half of all patients managed with REBOA had neurologically intact survival. The high death rate in resuscitative thoracotomy and differences in patient cohorts limit direct comparison.

ALDH2 inactivating mutation (ALDH2*2) is the most abundant mutation leading to bone morphological aberration. Osteoporosis has long been associated with changes in bone biomaterial in elderly populations. Such changes can be exacerbated with elevated ethanol consumption and in subjects with impaired ethanol metabolism, such as carriers of aldehyde dehydrogenase 2 (ALDH2)-deficient gene, ALDH2*2. So far, little is known about bone compositional changes besides a decrease in mineralization. Raman spectroscopic imaging has been utilized to study the changes in overall composition of C57BL/6 female femur bone sections, as well as in compound spatial distribution. Raman maps of bone sections were analyzed using multilinear regression with these four isolated components, resulting in maps of their relative distribution. A 15-week treatment of both wild-type (WT) and ALDH2*2/*2 mice with 20% ethanol in the drinking water resulted in a significantly lower mineral content (p  0.4). Highly localized islets of elongated adipose tissue were observed on most maps. Elevated fat content was found in ALDH2*2 knock-in mice consuming ethanol (p