Flow Cytometric Assessment of Malignant Hematologic Disorders.

Multiparameter flow cytometry (MPF) is an essential component of the diagnostic workup of hematologic malignancies. Recently developed tools have expanded the utility of MPF in detecting T-cell clonality and myelomonocytic dysplasia. Minimal/measurable residual disease analysis has long been established as critical in the management of B-lymphoblastic leukemia and is emerging as a useful tool in myeloid malignancies. With the continued increased complexity of MPF assays, emerging tools for data collection and analysis will allow users to take full advantage of MPF in the diagnosis of hematologic disease.

Hospitalizations among family members increase the risk of MRSA infection in a household.

OBJECTIVE: Estimate the risk for household transmission of Methicillin-Resistant Staphylococcus aureus (MRSA) following exposure to infected family members or family members recently discharged from a hospital. DESIGN: Analysis of monthly MRSA incidence from longitudinal insurance claims using the Merative MarketScan Commercial and Medicare (2001-2021) databases. SETTING: Visits to inpatient, emergency department, and outpatient settings. PATIENTS: Households with ≥2 family members enrolled in the same insurance plan for the entire month. METHODS: We estimated a monthly incidence model, where enrollees were binned into monthly enrollment strata defined by demographic, patient, and exposure characteristics. Monthly incidence within each stratum was computed, and a regression analysis was used to estimate the incidence rate ratio (IRR) associated with household exposures of interest while accounting for potential confounding factors. RESULTS: A total of 157,944,708 enrollees were included and 424,512 cases of MRSA were identified. Across all included enrollees, exposure to a family member with MRSA in the prior 30 days was associated with significantly increased risk of infection (IRR: 71.03 [95% CI, 67.73-74.50]). After removing enrollees who were hospitalized or exposed to a family member with MRSA, exposure to a family member who was recently discharged from the hospital was associated with increased risk of infection (IRR: 1.44 [95% CI, 1.39-1.49]) and the risk of infection increased with the duration of the family member's hospital stay (P value < .001). CONCLUSIONS: Exposure to a recently hospitalized and discharged family member increased the risk of MRSA infection in a household even when the hospitalized family member was not diagnosed with MRSA.

Intraduodenal Fecal Microbiota Transplantation Ameliorates Gut Atrophy and Cholestasis in a Novel Parenteral Nutrition Piglet Model.

BACKGROUND: Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury. METHODS: Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A) or TPN + intraduodenal fecal microbiota transplant (TPN-FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16s rRNA sequencing. PERMANOVA, Jaccard and Bray-Curtis metrics were performed. RESULTS: Significant bilirubin elevation in TPN and TPN-A vs EN (p<0.0001) was prevented with FMT. IFN-G, TNF-alpha, IL-beta, IL-8 and LPS were significantly higher in TPN (p=0.009/0.001/0.043/0.011/<0.0001), with preservation upon FMT. Significant gut-atrophy by villous/crypt ratio in TPN (p<0.0001) and TPN-A (p=0.0001) vs EN was prevented by FMT (p=0.426 vs EN). Microbiota profiles using Principal Coordinate Analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN altered gut barrier was preserved upon FMT. Upregulated CYP7A1 and BSEP in TPN and TPN-A, and downregulatedFGFR4, EGF, FXR and TGR5 vs EN was prevented by FMT. CONCLUSION: This study provides novel evidence of prevention of gut atrophy, liver injury and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores importance of gut microbes as prime targets for therapeutics and drug discovery.

Improving Patient Safety Through Proper Ordering and Administration of Andexanet Alfa.

Objective: To evaluate prescribing practices for the anti-Xa reversal agent, andexanet alfa, to identify challenges in ordering and administering this medication, and to offer recommendations to improve patient safety. Patients and Methods: This retrospective study reviewed all adult patients treated with andexanet alfa (AA) at a single institution between January 1, 2018, and March 31, 2020. We identified ordering and administration benchmarks based on recommendations from previous clinical trials on AA. We then reviewed these medical records to determine compliance with these benchmarks. We also collected data related to thrombotic complications and mortality. Results: Twenty-two AA dosing sets (loading and infusion dose) were given to 20 patients. Eight (36%) dosing sets met our ordering benchmarks regarding appropriate dose, time since last direct oral anticoagulants, urgency of administration, and documentation. Three (14%) dosing sets met the administrative benchmarks of being started within 30 minutes of the initial order, and 13 (59%) dosing sets had timely infusion of the infusion dose after the loading dose. No dosing set met all our administration benchmarks. There was 1 thrombotic event within 24 hours of the correct AA dose and 1 potential death related to AA. Conclusion: This study highlights challenges in ordering and administering AA at our institution and brings awareness to potential similar concerns at other institutions. These challenges also identified the need for optimized order sets, a streamlined administration process, and frequent provider education to improve patient safety.

Exercise-specific adaptations in human skeletal muscle: Molecular mechanisms of making muscles fit and mighty.

The mechanisms leading to a predominantly hypertrophied phenotype versus a predominantly oxidative phenotype, the hallmarks of resistance training (RT) or aerobic training (AT), respectively, are being unraveled. In humans, exposure of naïve persons to either AT or RT results in their skeletal muscle exhibiting generic 'exercise stress-related' signaling, transcription, and translation responses. However, with increasing engagement in AT or RT, the responses become refined, and the phenotype typically associated with each form of exercise emerges. Here, we review some of the mechanisms underpinning the adaptations of how muscles become, through AT, 'fit' and RT, 'mighty.' Much of our understanding of molecular exercise physiology has arisen from targeted analysis of post-translational modifications and measures of protein synthesis. Phosphorylation of specific residue sites has been a dominant focus, with canonical signaling pathways (AMPK and mTOR) studied extensively in the context of AT and RT, respectively. These alone, along with protein synthesis, have only begun to elucidate key differences in AT and RT signaling. Still, key yet uncharacterized differences exist in signaling and regulation of protein synthesis that drive unique adaptation to AT and RT. Omic studies are required to better understand the divergent relationship between exercise and phenotypic outcomes of training.

Direct tracking of H2 roaming reaction in real time.

Roaming is an unconventional type of molecular reaction where fragments, instead of immediately dissociating, remain weakly bound due to long-range Coulombic interactions. Due to its prevalence and ability to form new molecular compounds, roaming is fundamental to photochemical reactions in small molecules. However, the neutral character of the roaming fragment and its indeterminate trajectory make it difficult to identify experimentally. Here, we introduce an approach to image roaming, utilizing intense, femtosecond IR radiation combined with Coulomb explosion imaging to directly reconstruct the momentum vector of the neutral roaming H2, a precursor to H 3 + formation, in acetonitrile, CH3CN. This technique provides a kinematically complete picture of the underlying molecular dynamics and yields an unambiguous experimental signature of roaming. We corroborate these findings with quantum chemistry calculations, resolving this unique dissociative process.

A Scoping Review and Meta-Analysis of the Relations Between Cognition and Cochlear Implant Outcomes and the Effect of Quiet Versus Noise Testing Conditions.

OBJECTIVES: Evidence continues to emerge of associations between cochlear implant (CI) outcomes and cognitive functions in postlingually deafened adults. While there are multiple factors that appear to affect these associations, the impact of speech recognition background testing conditions (i.e., in quiet versus noise) has not been systematically explored. The two aims of this study were to (1) identify associations between speech recognition following cochlear implantation and performance on cognitive tasks, and to (2) investigate the impact of speech testing in quiet versus noise on these associations. Ultimately, we want to understand the conditions that impact this complex relationship between CI outcomes and cognition. DESIGN: A scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed on published literature evaluating the relation between outcomes of cochlear implantation and cognition. The current review evaluates 39 papers that reported associations between over 30 cognitive assessments and speech recognition tests in adult patients with CIs. Six cognitive domains were evaluated: Global Cognition, Inhibition-Concentration, Memory and Learning, Controlled Fluency, Verbal Fluency, and Visuospatial Organization. Meta-analysis was conducted on three cognitive assessments among 12 studies to evaluate relations with speech recognition outcomes. Subgroup analyses were performed to identify whether speech recognition testing in quiet versus in background noise impacted its association with cognitive performance. RESULTS: Significant associations between cognition and speech recognition in a background of quiet or noise were found in 69% of studies. Tests of Global Cognition and Inhibition-Concentration skills resulted in the highest overall frequency of significant associations with speech recognition (45% and 57%, respectively). Despite the modest proportion of significant associations reported, pooling effect sizes across samples through meta-analysis revealed a moderate positive correlation between tests of Global Cognition (r = +0.37, p < 0.01) as well as Verbal Fluency (r = +0.44, p < 0.01) and postoperative speech recognition skills. Tests of Memory and Learning are most frequently utilized in the setting of CI (in 26 of 39 included studies), yet meta-analysis revealed nonsignificant associations with speech recognition performance in a background of quiet (r = +0.30, p = 0.18), and noise (r = -0.06, p = 0.78). CONCLUSIONS: Background conditions of speech recognition testing may influence the relation between speech recognition outcomes and cognition. The magnitude of this effect of testing conditions on this relationship appears to vary depending on the cognitive construct being assessed. Overall, Global Cognition and Inhibition-Concentration skills are potentially useful in explaining speech recognition skills following cochlear implantation. Future work should continue to evaluate these relations to appropriately unify cognitive testing opportunities in the setting of cochlear implantation.

Comparison Between Black Non-Hispanic and White Non-Hispanic Simultaneous Pancreas-Kidney Transplant Candidates and Recipients.

INTRODUCTION: This study examined simultaneous pancreas-kidney transplant (SPKt) in Black and White patients to identify disparities in transplantation, days on the waitlist, and reasons for SPKt waitlist removal. METHODS: Using the United Network for Organ Sharing Standard Transplant Analysis and Research file, patients between January 1, 2009, and May 31, 2021, were included. Three cohorts (overall, SPKt recipients only, and those not transplanted) were selected using propensity score matching. Conditional logistic regression was used for categorical outcomes. Days on the waitlist were compared using negative binomial regression. RESULTS: Black patients had increased odds of receiving a  SPKt (OR, 1.25 [95% CI, 1.11-1.40], p < 0.001). White patients had increased odds of receiving a kidney-only transplant (OR 0.48 [95% CI, 0.38-0.61], p < 0.001), and specifically increased odds of receiving a living donor kidney (OR 0.34 [0.25-0.45], p < 0.001). CONCLUSION: This study found that Black patients are more likely to receive a SPKt. Results suggest that there are opportunities for additional inquiry related to patient removal from the waitlist, particularly considering White patients received or accepted more kidney-only transplants and were more likely to receive a living donor kidney-only transplant.

Baseline Frailty Measured by the Risk Analysis Index and 30-Day Mortality After Surgery for Spinal Malignancy: Analysis of a Prospective Registry (2011-2020).

OBJECTIVE: To evaluate the prognostic utility of baseline frailty, measured by the Risk Analysis Index (RAI), for prediction of postoperative mortality among patients with spinal malignancy (SM) undergoing resection. METHODS: SM surgery cases were queried from the American College of Surgeons - National Surgical Quality Improvement Program database (2011-2020). The relationship between preoperative RAI frailty score and increasing rate of primary endpoint (mortality or discharge to hospice within 30 days, "mortality/hospice") were assessed. Discriminatory accuracy was assessed by computation of C-statistics (with 95% confidence interval [CI]) in receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 2,235 cases were stratified by RAI score: 0-20, 22.7%; 21-30, 11.9%; 31-40, 54.7%; and ≥ 41, 10.7%. The rate of mortality/hospice was 6.5%, which increased linearly with increasing RAI score (p < 0.001). RAI was also associated with increasing rates of major complication, extended length of stay, and nonhome discharge (all p < 0.05). The RAI demonstrated acceptable discriminatory accuracy for prediction of primary endpoint (C-statistic, 0.717; 95% CI, 0.697-0.735). In pairwise ROC comparison, RAI demonstrated superiority versus modified frailty index-5 and chronological age (p < 0.001). CONCLUSION: Preoperative frailty, as measured by RAI, is a robust predictor of mortality/ hospice after SM surgery. The frailty score may be applied in clinical settings using a user-friendly calculator, deployed here: https://nsgyfrailtyoutcomeslab.shinyapps.io/spinalMalignancyRAI/.

Do All Postoperative Vancouver B2 Fractures Require Revision Arthroplasty With Cementless Stems?

Background: Management of periprosthetic fractures has been guided by the Vancouver classification, which recommends revision for fractures around a loose femoral implant (B2). New studies have challenged this approach, demonstrating acceptable outcomes with internal fixation. This study evaluates our experience with Vancouver B2 fractures, comparing internal fixation to femoral revision. We hypothesized that in select cases with cementless stems, internal fixation would provide acceptable results with reduced morbidity. Methods: A retrospective review was performed of periprosthetic hip fractures treated at our institution between 1 January 2012 and 4 November 2022. We excluded patients who did not have prior radiographs and evidence of stem subsidence, suggestive of a Vancouver B2 fracture. Thirteen patients were included in the analysis. Results: Four patients (31%) underwent revision of the femoral component, 4 patients (31%) underwent plating, and 5 patients (38%) underwent internal fixation with cerclage cabling. The average operative duration was 158 minutes, 203 minutes, and 62 minutes for the revision, plating, and cabling cohorts, respectively (P = .009). Blood loss was 463 cc, 510 cc, and 90 cc for the revision, plating, and cabling cohorts, respectively (P = .036). Three patients in both the revision and plating cohorts each received a transfusion (75%), whereas no patients in the cabling cohort required a transfusion (P = .033). All patients demonstrated fracture healing on the postoperative radiographs. No patients required additional surgery during the follow-up period. Conclusions: We have demonstrated that Vancouver B2 periprosthetic fractures with intact lateral cortices may be treated with internal fixation with cerclage cabling with excellent results.

Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis.

The pathogenesis of anorexia nervosa (AN) has been hypothesized to involve several biological systems. However, reliable biomarkers for AN have yet to be established. This study was aimed to identify statistically significant and clinically meaningful peripheral biomarkers associated with AN. A systematic literature search was conducted to identify studies published in English from inception until 30 June 2022. We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers and found that acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls. Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls. Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation. Scientific investigation into peripheral biomarkers may ultimately yield breakthroughs in personalized clinical care for AN.

A retrospective epidemiological study of sarcoptic mange in koalas (Phascolarctos cinereus) using wildlife carer admission records.

Outbreaks of sarcoptic mange are sporadically reported in koala populations across Australia, but disease characteristics (e.g., distribution across the body) remain poorly understood. In an area of Northern Victoria regular cases coming into care suggest mange may have become enzootic, and here we characterise those koala mange admission records. In 18% (n = 10) of mange affected koala reports that had a recorded outcome (n = 55), the animals died before the carers could locate them, and of the remaining 45 koalas that were alive upon carer arrival, 80% (n = 36) had to be euthanised due to severe mange. The number of admissions varied among years (highest observed in 2019), and over 60% of affected koala admissions were male. Male admissions peaked in austral spring and again in late austral summer-autumn (mating and birthing seasons), with female admissions only exhibiting the latter peak (birthing season). Fissures of the epidermis of the front paws occurred in 100% of admitted koalas, with 70% also showing these signs elsewhere on ventral surfaces or limbs. Only male koalas had signs of mange on the chest and face, and only female koalas had signs of mange on their back. Collectively, this study suggests sarcoptic mange can be a severe disease in koalas, and that male koalas may play an important role in seasonal transmission dynamics. We discuss how these findings may help inform intervention strategies.

HIARA study protocol: impacts of artificial coral reef development on fisheries, human livelihoods and health in southwestern Madagascar.

The Health Impacts of Artificial Reef Advancement (HIARA; in the Malagasy language, "together") study cohort was set up in December 2022 to assess the economic and nutritional importance of seafood for the coastal Malagasy population living along the Bay of Ranobe in southwestern Madagascar. Over the course of the research, which will continue until at least 2026, the primary question we seek to answer is whether the creation of artificial coral reefs can rehabilitate fish biomass, increase fish catch, and positively influence fisher livelihoods, community nutrition, and mental health. Through prospective, longitudinal monitoring of the ecological and social systems of Bay of Ranobe, we aim to understand the influence of seasonal and long-term shifts in marine ecological resources and their benefits to human livelihoods and health. Fourteen communities (12 coastal and two inland) were enrolled into the study including 450 households across both the coastal (n = 360 households) and inland (n = 90 households) ecosystems. In the ecological component, we quantify the extent and health of coral reef ecosystems and collect data on the diversity and abundance of fisheries resources. In the social component, we collect data on the diets, resource acquisition strategies, fisheries and agricultural practices, and other social, demographic and economic indicators, repeated every 3 months. At these visits, clinical measures are collected including anthropometric measures, blood pressure, and mental health diagnostic screening. By analyzing changes in fish catch and consumption arising from varying distances to artificial reef construction and associated impacts on fish biomass, our cohort study could provide valuable insights into the public health impacts of artificial coral reef construction on local populations. Specifically, we aim to assess the impact of changes in fish catch (caused by artificial reefs) on various health outcomes, such as stunting, underweight, wasting, nutrient intake, hypertension, anxiety, and depression.

Dietary Features Are Associated with Differences in the Urinary Microbiome in Clinically Healthy Adult Dogs.

Nutrition plays an important role in shaping the gut microbiome composition, although the impact of diet on the urinary microbiome (i.e., urobiome) remains unknown. The aim of this pilot study was to discover how nutritional features affect the diversity and composition of the urobiome in dogs. Dietary histories were obtained for 15 clinically healthy adult dogs, including limited nutrient (protein, fat, crude fiber), commercial diet brand, and dietary diversity profiles. The urine samples were collected via cystocentesis, followed by sequencing of the bacterial 16S rRNA gene. The data were analyzed to determine associations between major nutrients and dietary sources with the urobiome's composition. The protein, fat, and crude fiber contents had no statistically significant effect on the alpha or beta diversity. However, the beta diversity values differed (PERMANOVA; p = 0.017, R2 = 0.10) between dogs fed one commercial diet brand compared to dogs consuming any other brand. The beta diversity values also differed (p = 0.019, R2 = 0.10) between dogs consuming more diverse daily diets compared to those consuming less diverse diets (≥3 or <3 unique food sources, respectively). Overall, the results of this pilot study suggest that diet might impact the urobiome and support further exploration of the relationship between diet and the urobiome's composition in dogs.

Neuropsychological profile associated with financial exploitation vulnerability in older adults without dementia.

Objective: Reports of financial exploitation have steadily increased among older adults. Few studies have examined neuropsychological profiles for individuals vulnerable to financial exploitation, and existing studies have focused on susceptibility to scams, one specific type of financial exploitation. The current study therefore examines whether a general measure of financial exploitation vulnerability is associated with neuropsychological performance in a community sample. Methods: A sample (n = 116) of adults aged 50 or older without dementia completed a laboratory visit that measures physical and psychological functioning and a neuropsychological assessment, the Uniform Data Set-3 (UDS-3) and California Verbal Learning Test-II. Results: After covarying for demographics, current medical problems, financial literacy, and a global cognition screen, financial exploitation vulnerability was negatively associated with scores on the Multilingual Naming Test, Craft Story Recall and Delayed Recall, California Verbal Learning Test-II Delayed Recall and Recognition Discriminability, Phonemic Fluency, and Trails B. Financial exploitation vulnerability was not associated with performance on Digit Span, Semantic Fluency, Benson Complex Figure Recall, or Trails A. Conclusions: Among older adults without dementia, individuals at higher risk for financial exploitation demonstrated worse verbal memory, confrontation naming, phonemic fluency, and set-shifting. These tests are generally sensitive to Default Mode Network functioning and Alzheimer's Disease neuropathology. Longitudinal studies in more impaired samples are warranted to further corroborate and elucidate these relationships.

Cytokines in PD-1 immune checkpoint inhibitor adverse events and implications for the treatment of uveitis.

Immune checkpoint inhibitors (ICI) such as Programmed cell Death 1 (PD-1) inhibitors have improved cancer treatment by enhancing the immune system's ability to target malignant cells. Their use is associated with immune-related adverse events (irAEs), including uveitis. The profile of pro-inflammatory cytokines underlying Anti-PD-1-induced uveitis shares significant overlap with that of non-infectious uveitis. Current corticosteroid treatments for uveitis while effective are fraught with vision threatening side effects. The cytokine profile in ICI-related uveitis has a large overlap with that of noninfectious uveitis, this overlap strongly supports the potential for therapy that activates the PD-1 axis in the eye to treat uveitis. Indeed, ICI related uveitis often resolves with cessation of the ICI, restoring the endogenous PD-1 axis. The potential benefit of targeting many pro-inflammatory cytokines via local PD-1 axis activation is mitigating ocular inflammation while minimizing adverse effects.

Escaping the benthos with Coral Reef Arks: effects on coral translocation and fish biomass.

Anthropogenic stressors like overfishing, land based runoff, and increasing temperatures cause the degradation of coral reefs, leading to the loss of corals and other calcifiers, increases in competitive fleshy algae, and increases in microbial pathogen abundance and hypoxia. To test the hypothesis that corals would be healthier by moving them off the benthos, a common garden experiment was conducted in which corals were translocated to midwater geodesic spheres (hereafter called Coral Reef Arks or Arks). Coral fragments translocated to the Arks survived significantly longer than equivalent coral fragments translocated to Control sites (i.e., benthos at the same depth). Over time, average living coral surface area and volume were higher on the Arks than the Control sites. The abundance and biomass of fish were also generally higher on the Arks compared to the Control sites, with more piscivorous fish on the Arks. The addition of Autonomous Reef Monitoring Structures (ARMS), which served as habitat for sessile and motile reef-associated organisms, also generally significantly increased fish associated with the Arks. Overall, the Arks increased translocated coral survivorship and growth, and exhibited knock-on effects such as higher fish abundance.

Sub-genomic flaviviral RNA elements increase the stability and abundance of recombinant AAV vector transcripts.

Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE). Further dissection of engineered transcripts revealed that sfRNA elements (i) require incorporation in cis within the 3' untranslated region (UTR) of AAV genomes, (ii) require minimal dumbbell structures to exert the observed effects, and (iii) can stabilize AAV transcripts independent of 5'-3' exoribonuclease 1 (XRN1)-mediated decay. Additionally, preliminary in vivo assessment of AAV vectors bearing sfRNA elements in mice achieved increased transcript abundance and expression in cardiac tissue. Leveraging the functional versatility of engineered viral RNA elements may help improve the potency of AAV vector-based gene therapies. IMPORTANCE: Viral RNA elements can hijack host cell machinery to control stability of transcripts and consequently, infection. Studies that help better understand such viral elements can provide insights into antiviral strategies and also potentially leverage these features for therapeutic applications. In this study, by incorporating structured flaviviral RNA elements into recombinant adeno-associated viral (AAV) vector genomes, we show improved AAV transcript stability and transgene expression can be achieved, with implications for gene transfer.

Practice Patterns for Acute Asthma Exacerbation in Adult Patients Admitted to US Intensive Care Units.

RATIONALE: Guidelines recommend systemic corticosteroids and inhaled beta-agonists for patients with severe asthma exacerbation admitted to intensive care units (ICUs). The benefits and utilization of adjunct treatments after guideline recommended first-line treatments have been initiated are unclear. METHODS: Using the Premier Inc. PINC AI multicenter database (2016-2022), we sought to explore the use of adjunct interventions (medications [e.g., magnesium, leukotriene inhibitors, terbutaline, heliox]; and procedures [e.g., invasive and non-invasive mechanical ventilation]) for adult patients admitted to United States (US) ICUs with acute asthma exacerbations. We used hierarchical generalized linear models to calculate risk-adjusted rates of adjunct interventions and quantified between-hospital variation in adjunct interventions using the intraclass correlation coefficient (ICC - higher values correspond to higher between hospital variation). We then used K-means clustering to identify groups of hospitals with similar risk-adjusted practice profiles of all adjunct treatments and examined associations between identified hospital clusters and patient outcomes. RESULTS: We identified 62,392 patients from 961 hospitals for inclusion. Adjunct interventions with the highest between hospital variation after risk-adjustment were heliox (ICC 91%), inhaled steroids (ICC 23%), invasive mechanical ventilation (ICC 21%), terbutaline (ICC 22%), paralytics (ICC 16%), and non-invasive ventilation (ICC 15%). K-means clustering identified two distinct hospital clusters: patients admitted to cluster 1 hospitals (399 hospitals) had higher risk-adjusted rates of non-invasive ventilation (51% vs 33%) compared to patients admitted to cluster 2 hospitals (234 hospitals) which had higher risk-adjusted rates of invasive mechanical ventilation (63% vs 30%). Cluster 2 was associated with fewer hospital free days (beta -0.75 days, CI -0.95, -0.55 days) and increased in-hospital mortality (aOR 1.28, CI 1.17, 1.40). CONCLUSIONS: The use of adjunct interventions for patients with severe asthma exacerbations vary widely across US hospitals; however, hospitals generally fall into two clusters differentiated primarily by the use of invasive or non-invasive mechanical ventilation. Our results help to inform usual care arms of future comparative effectiveness studies and efforts to standardize asthma practice.