Synthesis and antibacterial action of 3',6'-disubstituted spectinomycins.

Spectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6'-position to produce trospectomycin and to the 3'-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation of three 3',6'-disubstituted spectinomycin analogs: trospectinamide, N-benzyl linked aminomethyl, and N-ethylene linked aminomethyl trospectomycins. Computational experiments predicted that these disubstituted analogs would be capable of binding within the SPC ribosomal binding site. The new analogs were synthesized from trospectomycin, adapting the previously established routes for the spectinamide and aminomethyl spectinomycin series. In a cell-free translation assay, the disubstituted analogs showed ribosomal inhibition similar to spectinomycin or trospectomycin. These disubstituted analogs demonstrated inhibitory MIC activity against various bacterial species with the 3'-modification dictating spectrum of activity, leading to improved activity against mycobacterium species. Notably, N-ethylene linked aminomethyl trospectomycins exhibited increased potency against Mycobacterium abscessus and trospectinamide displayed robust activity against M. tuberculosis, aligning with the selective efficacy of spectinamides. The study also found that trospectomycin is susceptible to efflux in M. tuberculosis and M. abscessus. These findings contribute to the understanding of the structure-activity relationship of spectinomycin analogs and can guide the design and synthesis of more effective spectinomycin compounds.

Comparing conventional and modified Seldinger techniques using a micro-insertion kit for PICC placement in neonates: a retrospective cohort study.

Objective: This study aims to assess the comparative effectiveness of a conventional splitting needle or a peelable cannula vs. the modified Seldinger technique (MST) by utilizing a dedicated micro-insertion kit across various clinically significant metrics, including insertion success, complications, and catheter-related infections. Methods: We conducted a retrospective observational cohort study using an anonymized data set spanning 3 years (2017-2019) in a large tertiary-level neonatal intensive care unit in Qatar. Results: A total of 1,445 peripherally inserted central catheter (PICC) insertion procedures were included in the analysis, of which 1,285 (89%) were successful. The primary indication for insertion was mainly determined by the planned therapy duration, with the saphenous vein being the most frequently selected blood vessel. The patients exposed to MST were generally younger (7 ± 15 days vs. 11 ± 26 days), but exhibited similar mean weights and gestational ages. Although not statistically significant, the MST demonstrated slightly higher overall and first-attempt insertion success rates compared to conventional methods (91 vs. 88%). However, patients undergoing conventional insertion techniques experienced a greater incidence of catheter-related complications (p < 0.001). There were 39 cases of catheter-related bloodstream infections (CLABSI) in the conventional group (3.45/1,000 catheter days) and eight cases in the MST group (1.06/1,000 catheter days), indicating a statistically significant difference (p < 0.001). Throughout the study period, there was a noticeable shift toward the utilization of the MST kit for PICC insertions. Conclusion: The study underscores the viability of MST facilitated by an all-in-one micro kit for neonatal PICC insertion. Utilized by adept and trained inserters, this approach is associated with improved first-attempt success rates, decreased catheter-related complications, and fewer incidences of CLABSI. However, while these findings are promising, it is imperative to recognize potential confounding factors. Therefore, additional prospective multicenter studies are recommended to substantiate these results and ascertain the comprehensive benefits of employing the all-in-one kit.

Vital Signs: Drowning Death Rates, Self-Reported Swimming Skill, Swimming Lesson Participation, and Recreational Water Exposure - United States, 2019-2023.

Introduction: Drowning is the cause of approximately 4,000 U.S. deaths each year and disproportionately affects some age, racial, and ethnic groups. Infrastructure disruptions during the COVID-19 pandemic, including limited access to supervised swimming settings, might have affected drowning rates and risk. Data on factors that contribute to drowning risk are limited. To assess the potential impact of the pandemic on drowning death rates, pre- and post-COVID-19 pandemic rates were compared. Methods: National Vital Statistics System data were used to compare unintentional drowning death rates in 2019 (pre-COVID-19 pandemic onset) with those in 2020, 2021, and 2022 (post-pandemic onset) by age, sex, and race and ethnicity. National probability-based online panel survey (National Center for Health Statistics Rapid Surveys System) data from October-November 2023 were used to describe adults' self-reported swimming skill, swimming lesson participation, and exposure to recreational water. Results: Unintentional drowning death rates were significantly higher during 2020, 2021, and 2022 compared with those in 2019. In all years, rates were highest among children aged 1-4 years; significant increases occurred in most age groups. The highest drowning rates were among non-Hispanic American Indian or Alaska Native and non-Hispanic Black or African American persons. Approximately one half (54.7%) of U.S. adults reported never having taken a swimming lesson. Swimming skill and swimming lesson participation differed by age, sex, and race and ethnicity. Conclusions and Implications for Public Health Practice: Recent increases in drowning rates, including those among populations already at high risk, have increased the urgency of implementing prevention strategies. Basic swimming and water safety skills training can reduce the risk for drowning. Addressing social and structural barriers that limit access to this training might reduce drowning deaths and inequities. The U.S. National Water Safety Action Plan provides recommendations and tools for communities and organizations to enhance basic swimming and water safety skills training.

CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.

PURPOSE: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system. METHODS: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences. RESULTS: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD, encoding dihydropyrimidine dehydrogenase. Genome sequencing identified compound heterozygosity in 2 patients for missense variants in CIAO1, encoding cytosolic iron-sulfur assembly component 1, and homozygosity for an in-frame 3-nucleotide deletion in MMS19, encoding the MMS19 homolog, cytosolic iron-sulfur assembly component, in the third patient. Profound alterations in the proteome, metabolome, and lipidome were observed in patient-derived fibroblasts. We confirmed the detrimental effect of deficiencies in CIAO1 and MMS19 in zebrafish models. CONCLUSION: A general failure of cytosolic and nuclear iron-sulfur protein maturation caused pleiotropic effects. The critical function of the cytosolic iron-sulfur protein assembly machinery for antiviral host defense may well explain the recurrent severe infections occurring in our patients.

Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus.

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections.

Cause-Specific Mortality Among Adults Aged ≥65 Years in the United States, 1999 Through 2020.

OBJECTIVE: Reports on recent mortality trends among adults aged ≥65 years are lacking. We examined trends in the leading causes of death from 1999 through 2020 among US adults aged ≥65 years. METHODS: We used data from the National Vital Statistics System mortality files to identify the 10 leading causes of death among adults aged ≥65 years. We calculated overall and cause-specific age-adjusted death rates and then calculated the average annual percentage change (AAPC) in death rates from 1999 through 2020. RESULTS: The overall age-adjusted death rate decreased on average by 0.5% (95% CI, -1.0% to -0.1%) per year from 1999 through 2020. Although rates for 7 of the top 10 causes of death decreased significantly, the rates of death from Alzheimer disease (AAPC = 3.0%; 95% CI, 1.5% to 4.5%) and from unintentional injuries (AAPC = 1.2%; 95% CI, 1.0% to 1.4%), notably falls (AAPC = 4.1%; 95% CI, 3.9% to 4.3%) and poisoning (AAPC = 6.6%; 95% CI, 6.0% to 7.2%), increased significantly. CONCLUSION: Public health prevention strategies and improved chronic disease management may have contributed to decreased rates in the leading causes of death. However, longer survival with comorbidities may have contributed to increased rates of death from Alzheimer disease and unintentional falls.

Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration.

T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes. Here, we used flow cytometry and single-cell RNA sequencing to identify a broader role for NCOR1 and NCOR2 in regulating thymocyte development. Using Cd4-cre mice, we found that conditional deletion of NCOR2 had no effect on thymocyte development, whereas conditional deletion of NCOR1 had a modest effect. In contrast, Cd4-cre x Ncor1f/f x Ncor2f/f mice exhibited a significant block in thymocyte development at the DP to SP transition. Combined NCOR1/2 deletion resulted in increased signaling through the T cell receptor, ultimately resulting in elevated BIM expression and increased negative selection. The NF-κB, NUR77, and MAPK signaling pathways were also upregulated in the absence of NCOR1/2, contributing to altered CD4/CD8 lineage commitment, TCR rearrangement, and thymocyte emigration. Taken together, our data identify multiple critical roles for the combined action of NCOR1 and NCOR2 over the course of thymocyte development.

Exploring professionals' views regarding prenatal counselling in congenital diaphragmatic hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a congenital malformation in which the diaphragm and lungs are underdeveloped, leading to cardiorespiratory and other problems. This study aimed to explore professionals' views regarding prenatal counselling in CDH. METHODS: A qualitative study was performed among healthcare professionals involved in the care of CDH patients in Radboud university medical center Amalia Children's Hospital. Semi-structured interviews were conducted until saturation was achieved. Transcripts were qualitatively analysed to gain insight into professionals' views regarding counselling. RESULTS: Eighteen professionals with various backgrounds were included. The professionals agreed that the first counselling session should be soon after diagnosis and additional sessions should be offered. Concerning counselling content, participants considered explanation of the diagnosis, prognosis, short- and long-term consequences, treatment options and practical aspects important. As for decision-making about possible termination of pregnancy, all professionals emphasised the importance of the parental role, but the preferred parental involvement varied. Regarding practical aspects, preferred counsellors were a neonatologist, obstetrician, paediatric surgeon and/or medical social worker. Participants emphasised that the counselling should be adjusted to parents' needs. CONCLUSIONS: This study gained insight into professionals' views regarding the timeline, content, decision-making process, and practical aspects of prenatal counselling in CDH.

The use of whole-body trauma CT should be based on mechanism of injury: A risk analysis of 3920 patients at a tertiary trauma centre.

BACKGROUND: Mechanism of injury (MOI) plays a significant role in a decision to perform whole-body computed tomography (CT) imaging for trauma patients. Various mechanisms have unique patterns of injury and therefore form an important variable in decision making. METHODS: Retrospective cohort study including all patients >18 years old who received a whole-body CT scan between 1 January 2019 and 19 February 2020. The outcomes were divided into CT 'positive' if any internal injuries were detected and CT 'negative' if no internal injuries were detected. The MOI, vital sign parameters, and other relevant clinical examination findings at presentation were recorded. RESULTS: 3920 patients met the inclusion criteria, of which 1591 (40.6%) had a positive CT. The most common MOI was fall from standing height (FFSH), accounting for 23.0%, followed by motor vehicle accident (MVA), accounting for 22.4%. Covariates significantly associated with a positive CT included age, MVA >60 km/h, motor bike, bicycle, or pedestrian accident >30 km/h, prolonged extrication >30 min, fall from height above standing, penetrating chest or abdominal injury, as well as hypotension, neurological deficit, or hypoxia on arrival. FFSH was shown to reduce the risk of a positive CT overall, however, sub-analysis of FFSH in patients >65 years showed a significant association with a positive CT (OR 2.34, p < 0.001) compared to <65 years. CONCLUSIONS: Pre-arrival information including MOI and vital signs have significant impact on identifying subsequent injuries with CT imaging. In high energy trauma, we should consider the need for whole-body CT based on MOI alone regardless of the clinical examination findings. However, for low-energy trauma, including FFSH, in the absence of clinical examination findings which support an internal injury, a screening whole-body CT is unlikely to yield a positive result, particularly in the age group <65yo.

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease.

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Hemostatic Complications During Neonatal Extracorporeal Membrane Oxygenation: Roller Pump and Centrifugal Pump Driven Circuits.

Recently three different neonatal extracorporeal membrane oxygenation (ECMO) circuits have been employed in our clinic. These circuits were compared for clotting and bleeding complications. Initially, we used an ECMO circuit containing a roller pump and venous bladder without severe complications. Manufacturing of circuit components was discontinued, necessitating the replacement of this circuit by a circuit with a centrifugal pump with 3/8 inch inlet and outlet. Acute increase of oxygenator resistance requiring emergency changeout became unexpectedly a regularly occurring complication. The increase in resistance was suspected to be caused by oxygenator clotting, although oxygenator function was preserved. To prevent this complication, we changed to a levitating centrifugal pump with 1/4 inch inlet and outlet, after which no oxygenator malfunction has been observed. Macroscopic and electron microscopic analysis demonstrates that small clots are formed within the circuit, presumably in or near the centrifugal pump, which are transported to the oxygenator and clog up the hollow fiber layer at the inlet side, barely penetrating the oxygenator beyond this first layer. Our results suggest that low blood velocities accompanied with recirculation of blood within or near the centrifugal pump and/or heat generation within the pump could contribute to the formation of these clots.

Retrospective analysis and prospective validation of an AI-based software for intracranial haemorrhage detection at a high-volume trauma centre.

Rapid detection of intracranial haemorrhage (ICH) is crucial for assessing patients with neurological symptoms. Prioritising these urgent scans for reporting presents a challenge for radiologists. Artificial intelligence (AI) offers a solution to enable radiologists to triage urgent scans and reduce reporting errors. This study aims to evaluate the accuracy of an ICH-detection AI software and whether it benefits a high-volume trauma centre in terms of triage and reducing diagnostic errors. A peer review of head CT scans performed prior to the implementation of the AI was conducted to identify the department's current miss-rate. Once implemented, the AI software was validated using CT scans performed over one month, and was reviewed by a neuroradiologist. The turn-around-time was calculated as the time taken from scan completion to report finalisation. 2916 head CT scans and reports were reviewed as part of the audit. The AI software flagged 20 cases that were negative-by-report. Two of these were true-misses that had no follow-up imaging. Both patients were followed up and exhibited no long-term neurological sequelae. For ICH-positive scans, there was an increase in TAT in the total sample (35.6%), and a statistically insignificant decrease in TAT in the emergency (- 5.1%) and outpatient (- 14.2%) cohorts. The AI software was tested on a sample of real-world data from a high-volume Australian centre. The diagnostic accuracy was comparable to that reported in literature. The study demonstrated the institution's low miss-rate and short reporting time, therefore any improvements from the use of AI would be marginal and challenging to measure.

Nuclear corepressors NCOR1/NCOR2 regulate B cell development, maintain genomic integrity and prevent transformation.

The nuclear corepressors NCOR1 and NCOR2 interact with transcription factors involved in B cell development and potentially link these factors to alterations in chromatin structure and gene expression. Herein, we demonstrate that Ncor1/2 deletion limits B cell differentiation via impaired recombination, attenuates pre-BCR signaling and enhances STAT5-dependent transcription. Furthermore, NCOR1/2-deficient B cells exhibited derepression of EZH2-repressed gene modules, including the p53 pathway. These alterations resulted in aberrant Rag1 and Rag2 expression and accessibility. Whole-genome sequencing of Ncor1/2 DKO B cells identified increased number of structural variants with cryptic recombination signal sequences. Finally, deletion of Ncor1 alleles in mice facilitated leukemic transformation, whereas human leukemias with less NCOR1 correlated with worse survival. NCOR1/2 mutations in human leukemia correlated with increased RAG expression and number of structural variants. These studies illuminate how the corepressors NCOR1/2 regulate B cell differentiation and provide insights into how NCOR1/2 mutations may promote B cell transformation.

Label and quantify mRNA molecules in live cell experiments using SunRISER and dNEMO.

Visualization of mRNA molecules in single cells has revealed their core mechanisms as well as sources of cell-to-cell and spatiotemporal heterogeneity. Here, we describe a protocol to label, visualize, and quantify mRNA molecules by time-lapse imaging with the capability of resolving mRNA molecules over durations of hours to days. We provide links to mRNA-labeling plasmids as well as free software for a semi-automated image analysis pipeline. For complete details on the use and execution of this protocol, please refer to Guo and Lee (2022) and Kowalczyk et al. (2021).

Spontaneous breathing approach in mild congenital diaphragmatic hernia: A resuscitation algorithm.

Background: Infants with a congenital diaphragmatic hernia (CDH) and expected mild pulmonary hypoplasia have an estimated survival rate of 90%. Current guidelines for delivery room management do not consider the individual patient's disease severity, but an individualized approach with spontaneous breathing instead of routine mechanical ventilation could be beneficial for the mildest cases. We developed a resuscitation algorithm for this individualized approach serving two purposes: improving the success rate by structuring the approach and providing a guideline for other centers. Methods: An initial algorithm was discussed with all local stakeholders. Afterwards, the resulting algorithm was refined using input from international experts. Results: Eligible CDH infants: left-sided defect, observed to expected lung-to-head ratio ≥50%, gestational age at birth ≥37.0 weeks, and no major associated structural or genetic abnormalities. To facilitate fetal-to-neonatal transition, we propose to start stabilization with non-invasive respiratory support and to adjust this individually. Conclusions: Infants with mild CDH might benefit from an individualized approach for neonatal resuscitation. Herein, we present an algorithm that could serve as guidance for centers implementing this.

Long-term imaging of individual mRNA molecules in living cells.

Single-cell imaging of individual mRNAs has revealed core mechanisms of the central dogma. However, most approaches require cell fixation or have limited sensitivity for live-cell applications. Here, we describe SunRISER (SunTag-based reporter for imaging signal-enriched mRNA), a computationally and experimentally optimized approach for unambiguous detection of single mRNA molecules in living cells. When viewed by epifluorescence microscopy, SunRISER-labeled mRNAs show strong signal to background and resistance to photobleaching, which together enable long-term mRNA imaging studies. SunRISER variants, using 8× and 10× stem-loop arrays, demonstrate effective mRNA detection while significantly reducing alterations to target mRNA sequences. We characterize SunRISER to observe mRNA inheritance during mitosis and find that stressors enhance diversity among post-mitotic sister cells. Taken together, SunRISER enables a glimpse into living cells to observe aspects of the central dogma and the role of mRNAs in rare and dynamical trafficking events.

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody. LY-CoV1404 potently neutralizes authentic SARS-CoV-2, B.1.1.7, B.1.351, and B.1.617.2. In pseudovirus neutralization studies, LY-CoV1404 potently neutralizes variants, including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved, except for N439 and N501. The binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The broad and potent neutralization activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants.

Validation and comparison of fall screening tools for predicting future falls among older adults.

BACKGROUND: Falls are the leading cause of injuries among older adults in the United States (US). Falls are preventable and clinicians are advised to screen for fall risk yearly. There are many falls screening tools and not all have been validated for their ability to predict future falls. METHODS: We enrolled 1905 community-dwelling older adults into a 13-month study using a probability-based representative panel of the US population recruited from NORC at the University of Chicago's National Frame. Respondents completed a baseline survey, 11 monthly fall calendars, and a final survey. The baseline survey included six falls screening tools (the Stay Independent, Three Key Questions (3KQ), a modified American Geriatric/British Geriatric tool, the short Falls Efficacy-1[FES-I]) and two single screening questions ("I have fallen in the past year" and "How many times did you fall in the past 12 months?"). The baseline and final survey collected demographic and health information, including falls. Sensitivity, specificity, positive and negative likelihood ratios, and corresponding 95% confidence intervals were calculated in SAS using weighted proportions. RESULTS: There were 1563 respondents who completed the final survey (completion rate 82%). Sensitivity estimates ranged from 22.5% for the short FES-I to 68.7% for the 3KQ. Specificity estimates ranged from 57.9% for the 3KQ to 89.4% for the short FES-I. CONCLUSIONS: Falls screening tools have varying sensitivity and specificity for predicting the occurrence of a fall in the following 12 months.

Immune Function After Splenic Artery Embolization for Blunt Trauma: Long-Term Assessment of CD27+ IgM B-Cell Levels.

Splenic artery embolization (SAE) plays a critical role in the treatment of high-grade splenic injury not requiring emergent laparotomy. SAE preserves splenic tissue, and growing evidence demonstrates preserved short-term splenic immune function after SAE. However, long-term function is less studied. Patients who underwent SAE for blunt abdominal trauma over a 10-year period were contacted for long-term follow-up. Sixteen participants (sex: women, 10, and men, 6; age: median, 34 years, and range, 18-67 years) were followed up at a median of 7.7 years (range, 4.7-12.8 years) after embolization. Splenic lacerations were of American Association for the Surgery of Trauma grades III to V, and 14 procedures involved proximal embolization. All individuals had measurable levels of IgM memory B cells (median, 14.30 as %B cells), splenic tissue present on ultrasound (median, 122 mL), and no history of severe infection since SAE. In conclusion, this study quantitatively demonstrated that long-term immune function remains after SAE for blunt abdominal trauma based on the IgM memory B cell levels.

Diagnostic accuracy of a commercially available deep-learning algorithm in supine chest radiographs following trauma.

OBJECTIVES: Trauma chest radiographs may contain subtle and time-critical pathology. Artificial intelligence (AI) may aid in accurate reporting, timely identification and worklist prioritisation. However, few AI programs have been externally validated. This study aimed to evaluate the performance of a commercially available deep convolutional neural network - Annalise CXR V1.2 (Annalise.ai) - for detection of traumatic injuries on supine chest radiographs. METHODS: Chest radiographs with a CT performed within 24 h in the setting of trauma were retrospectively identified at a level one adult trauma centre between January 2009 and June 2019. Annalise.ai assessment of the chest radiograph was compared to the radiologist report of the chest radiograph. Contemporaneous CT report was taken as the ground truth. Agreement with CT was measured using Cohen's κ and sensitivity/specificity for both AI and radiologists were calculated. RESULTS: There were 1404 cases identified with a median age of 52 (IQR 33-69) years, 949 males. AI demonstrated superior performance compared to radiologists in identifying pneumothorax (p = 0.007) and segmental collapse (p = 0.012) on chest radiograph. Radiologists performed better than AI for clavicle fracture (p = 0.002), humerus fracture (p < 0.0015) and scapula fracture (p = 0.014). No statistical difference was found for identification of rib fractures and pneumomediastinum. CONCLUSION: The evaluated AI performed comparably to radiologists in interpreting chest radiographs. Further evaluation of this AI program has the potential to enable it to be safely incorporated in clinical processes. ADVANCES IN KNOWLEDGE: Clinically useful AI programs represent promising decision support tools.