Associations between Histo-Blood Group Antigen Status in Mother-Infant Dyads and Infant Oral Rotavirus Vaccine Immunogenicity in rural Zimbabwe.

INTRODUCTION: Histo-blood group antigen (HBGA) phenotypes may contribute to poor oral rotavirus vaccine (RVV) immunogenicity, since rotavirus binds intestinal epithelial HBGA glycans, while maternal HBGA status shapes breastmilk composition, which influences the composition of the infant microbiome. We investigated associations between maternal/infant HBGA phenotypes and RVV immunogenicity in rural Zimbabwe. METHODS: We undertook salivary FUT2/FUT3 phenotyping in mother-infant pairs. Serum anti-rotavirus IgA was measured by ELISA. We explored adjusted associations between FUT2/FUT3 status and RVV seroconversion (primary outcome, N=322), and seropositivity and geometric mean titre (secondary outcomes, N=776). RESULTS: Infants of FUT2-positive or FUT3-positive women were less likely to seroconvert post-RVV than infants of FUT2-negative or FUT3-negative women (FUT2-positive 20.1% versus FUT2-negative 27.5%, adjusted relative risk (aRR) 0.47, 95%CI 0.26, 0.82; P=0.008; FUT3-positive 18.1% versus FUT3-negative 30.0%, aRR 0.45, 95%CI 0.25, 0.78; P=0.005). Compared to FUT2-positive infants with FUT2-positive mothers, FUT2-positive infants with FUT2-negative mothers were twice as likely to seroconvert (36.8% versus 21.9%, aRR 2.12, 95%CI 1.23, 3.63; P=0.006). Compared to FUT3-positive infants with FUT3-positive mothers, FUT3-positive infants with FUT3-negative mothers were three times as likely to seroconvert (48.3% versus 18.2%, aRR 2.99, 95%CI 1.82, 4.90; P<0.001). CONCLUSIONS: Maternal and infant FUT2 and FUT3 status influences infant RVV immunogenicity.

Key stakeholders' perspectives of illicit drug use and associated harms in the Northern Territory of Australia.

BACKGROUND: In the Northern Territory (NT) of Australia, there are significant evidence gaps about illicit drug use and harms, despite having established monitoring and reporting systems. This paper reports on illicit drug use, associated harms, contributing factors, service needs and priorities in the NT from the perspective and experiences of key stakeholders engaged in providing services for, or advocating on behalf of, people who use illicit drugs in the NT. METHODS: Face-to-face and online qualitative interviews were conducted with stakeholders across urban and remote locations in the NT. Key stakeholders were service providers, including acute and primary care clinicians, representatives of Aboriginal community controlled health organisations, lived experience advocates, peak body representatives and public health executives. Qualitative data were analysed thematically. RESULTS: Four researchers interviewed 21 participants across urban (62%), and remote areas (38%) of the NT. Themes identified were: (1) Illicit drug use and harms are diverse and distinct; (2) Client support needs are complex and influenced by co-morbidities, socio-demographic and cultural factors; (3) Priority population sub-groups need targeted strategies; (4) Local service strengths can be further developed and enhanced; (5) Local services need better resourcing; (6) Invest in progressive legislative and policy reforms; and (7) Improve routine monitoring and evaluation. CONCLUSIONS: Key stakeholders described illicit drug use, harms and contributing factors, which provided insights into the local challenges. Participants emphasised that clients have complex care needs, and further investment into targeted strategies are required to improve service engagement with priority groups. Service needs included greater understanding the role of dual diagnosis and its implementation and enhancing integrated and collaborative care in both primary health and acute care contexts. The voices of people with lived experience captured in this paper must inform local strategy and policy development relating to illicit drug use, in alignment with national strategy.

Psychosocial experiences of adolescents with tuberculosis in Cape Town.

Adolescents (10-19-years-old) account for almost 10% of the annual global tuberculosis (TB) incidence. Adolescents' experiences of TB care, TB stigma, and the consequences of TB for their relationships, schooling, and mental health are different, and often more severe, compared to younger children and adults. How TB impacts the lives of adolescents is not well described or understood. We aimed to locate adolescents' experiences of TB relative to their psychosocial contexts, describe the impact of TB on adolescents' wellbeing, and describe how TB and its treatment affects their socio-familial contexts. Teen TB was a prospective observational cohort study which recruited 50 adolescents with newly diagnosed TB disease (including both multidrug-resistant TB and drug-susceptible TB) in Cape Town, South Africa. A nested sub-sample of 20 adolescents were purposively sampled for longitudinal qualitative data collection. Nineteen participants completed all qualitative data collection activities between December 2020 and September 2021. Adolescents described their communities as undesirable places to live-rife with violence, poverty, and unemployment. The negative experiences of living in these conditions were exacerbated by TB episodes among adolescents or within their households. TB and its treatment disrupted adolescents' socio-familial connections; many participants described losing friendships and attachment to family members as people reacted negatively to their TB diagnosis. TB, inclusive of the experience of disease, diagnosis and treatment also negatively impacted adolescents' mental health. Participants reported feeling depressed, despondent, and at times suicidal. TB also disrupted adolescents' schooling and employment opportunities as adolescents were absent from school and college for substantial periods of time. Our findings confirm that adolescents' psychosocial experiences of TB are often highly negative, compounding underlying vulnerability. Future research should prioritize exploring the potential of social protection programmes providing adolescents and their families with psychosocial and economic support.

Exploring Revision Total Ankle Arthroplasty Failures A Comparison Between Failed and Successful Revision Cases.

This study assesses the comorbidities that are associated with failed revision total ankle arthroplasty (TAA) and explores the outcomes following a failed revision TAA. A retrospective analysis was conducted on a cohort of patients who underwent a revision TAA at a single institution from 2008 to 2022. Patients were identified as having revision failure if they required explantation, below-knee amputation (BKA), or a revision of either metal component. Statistical analysis was performed to identify any significant differences and summarize outcomes. The study included a total of 87 patients who underwent revision TAA with 12 patients who subsequently experienced revision failure. The revision TAA failure rate was 13.8%. There were higher rates of former smokers (58.3%; n = 7) and a history of diabetes (33.3%; n = 4) in the failure cohort, although these differences did not reach statistical significance. Limb salvage procedures were achieved in 11 cases (91.7%). Approaches for failed revision TAAs included arthrodesis (n = 5) with 2 isolated ankle arthrodesis (AA) and 3 tibio-talo-calcaneal (TTC) arthrodesis, an additional revision arthroplasty (n = 6), or amputation (n = 1). Ankle arthroplasty retention was successful in 6 cases (50.0%). Our results demonstrate that a second revision approach was chosen in half of the cases, underscoring its viability as a successful intervention according to patient preferences.Level of Evidence: III.

The outcomes of imagery-focused interventions in relation to distress in people with delusions: a systematic literature review.

BACKGROUND: Imagery-focused therapies within cognitive behavioural therapy are growing in interest and use for people with delusions. AIMS: This review aimed to examine the outcomes of imagery-focused interventions in people with delusions. METHOD: PsycINFO, PubMed, MEDLINE, Web of Science, EMBASE and CINAHL were systematically searched for studies that included a clinical population with psychosis and delusions who experienced mental imagery. The review was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and quality appraisal of all included papers was completed using the Crowe Critical Appraisal Tool. Information from included texts was extracted and collated in Excel, which informed the narrative synthesis of results. RESULTS: Of 2,736 studies identified, eight were eligible for inclusion and rated for quality with an average score of 70.63%. These studies largely supported their aims in reducing levels of distress and intrusiveness of imagery. Four of the eight studies used case series designs, two were randomised controlled trials, and two reported single case studies. It appears that interventions targeting mental imagery were acceptable and well tolerated within a population of people experiencing psychosis and delusions. CONCLUSIONS: Some therapeutic improvement was reported, although the studies consisted of mainly small sample sizes. Clinical implications include that people with a diagnosis of psychosis can engage with imagery-focused therapeutic interventions with limited adverse events. Future research is needed to tackle existing weaknesses of design and explore the outcomes of imagery interventions within this population in larger samples, under more rigorous methodologies.

Increased Sensitivity to Effort and Perception of Effort in People with Schizophrenia.

OBJECTIVE: Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations, calculations weighing the costs vs. the benefits of actions. Several reports have shown that people with schizophrenia display a reduced willingness to exert effort for monetary rewards when compared to controls. The primary goal of the current study was to further characterize reduced willingness to exert effort in schizophrenia by determining whether reduced willingness reflects (1) reduced sensitivity to reward, (2) increased sensitivity to effort, or (3) a combination of both. DESIGN: We assessed effort-cost decision-making in 30 controls and 30 people with schizophrenia, using 2 separate experimental tasks. Critically, one paradigm allowed for independent estimation of effects of reward and effort sensitivity on choice behavior. The other task isolated effort sensitivity by measuring effort in the absence of reward. Clinical interviews and self-report questionnaires were administered to people with schizophrenia to determine negative symptom severity. RESULTS: Across both tasks, we found evidence for reduced willingness to exert effort in people with schizophrenia compared to controls. Further, in both paradigms reduced willingness to exert effort was driven by increased sensitivity to effort in people with schizophrenia compared to controls. In contrast, measures of reward sensitivity did not significantly differ between groups. Surprisingly, we did not find correlations between task variables and measures of negative symptom severity. CONCLUSIONS AND RELEVANCE: These findings further specify prior work by identifying a specific contributory role for increased effort sensitivity in effort-cost decision-making deficits in schizophrenia.

Effect of RapidShockTM Implementation on Perishock Pause in Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Shorter pauses in cardiopulmonary resuscitation (CPR) are associated with better health outcomes after out-of-hospital cardiac arrest (OHCA). Our primary objective was to examine the effect of a RapidShockTM defibrillator software upgrade compared with standard defibrillator software on the length of perishock pause during care for OHCA among adults. Secondary objectives were to assess the effects of RapidShockTM on other CPR pauses. METHODS: We conducted a retrospective cohort study between September 1, 2015 and September 30, 2020. "Standard" cardiac defibrillator software in manual interpretation mode was used for CPR delivered on or before November 30, 2018, while "RapidShockTM" software (ZOLL® Medical Corporation) was used after this date. For each study group, we calculated the perishock, perianalysis, and total CPR pause; each CPR cycle was considered an independent event. We then calculated the median and interquartile range (IQR) for observed pauses with the "Standard" and "RapidShockTM" software. Percent change in median perishock pause (shockable rhythms), perianalysis pause (non-shockable rhythms), and total CPR pause were compared between CPR administered with each software using the Mann-Whitney test. RESULTS: There were 733 and 782 distinct CPR cycles administered using "Standard" and "RapidShockTM" software, respectively. A 31.8% reduction in median perishock pause was observed with "RapidShockTM" software compared with the "Standard" software (22.0 s (IQR 18.0 - 27.0 s) vs. 15.0 s (IQR 13.0 - 19.0 s); p < 0.01). The decrease in median perishock pause was driven by a reduction in the preshock phase (18 s vs. 10 s; 44.4% decrease in median pause; p < 0.01). No differences were observed in median perianalysis pause between the two groups. When combining shockable and non-shockable rhythms, we observed a reduction of 23.5% in median CPR pause (17.0 s (IQR 11.0 - 24.0 s) vs. 13s (IQR 10.0 - 17.0 s); p < 0.01). CONCLUSIONS: Overall, we observed that the use of "RapidShockTM" defibrillator software was associated with shorter CPR pauses compared with the "Standard" software. Additional studies are required to examine whether further reductions in CPR pauses may be achieved and to investigate associations between shorter CPR pauses and health outcomes.

RUNX1 interacts with lncRNA SMANTIS to regulate monocytic cell functions.

Monocytes, the circulating macrophage precursors, contribute to diseases like atherosclerosis and asthma. Long non-coding RNAs (lncRNAs) have been shown to modulate the phenotype and inflammatory capacity of monocytes. We previously discovered the lncRNA SMANTIS, which contributes to cellular phenotype expression by controlling BRG1 in mesenchymal cells. Here, we report that SMANTIS is particularly highly expressed in monocytes and lost during differentiation into macrophages. Moreover, different types of myeloid leukemia presented specific SMANTIS expression patterns. Interaction studies revealed that SMANTIS binds RUNX1, a transcription factor frequently mutated in AML, primarily through its Alu-element on the RUNT domain. RNA-seq after CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1 revealed an association with cell adhesion and both limited the monocyte adhesion to endothelial cells. Mechanistically, SMANTIS KO reduced RUNX1 genomic binding and altered the interaction of RUNX1 with EP300 and CBFB. Collectively, SMANTIS interacts with RUNX1 and attenuates monocyte adhesion, which might limit monocyte vascular egress.

Data-Driven Implementation Strategy to Optimise Clinician Behaviour Change at Scale in Complex Clinical Environments: A Multicentre Emergency Care Study.

AIM: To develop an evidence-driven, behaviour change focused strategy to maximise implementation and uptake of HIRAID (History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) in 30 Australian rural, regional and metropolitan emergency departments. DESIGN: An embedded, mixed-methods study. METHODS: This study is the first phase of a step-wedge cluster randomised control trial of HIRAID involving over 1300 emergency nurses. Concurrent quantitative and qualitative data were collected via an electronic survey sent to all nurses to identify preliminary barriers and enablers to HIRAID implementation. The survey was informed by the Theoretical Domains Framework, which is a synthesis of behavioural change theories that applies the science of intervention implementation in health care to effect change. Quantitative data were analysed using descriptive statistics and qualitative data with inductive content analysis. Data were then integrated to generate barriers and enablers to HIRAID implementation which were mapped to the Theoretical Domains Framework. Corresponding intervention functions and Behaviour Change techniques were selected and an overarching implementation strategy was developed through stakeholder consultation and application of the APEASE criteria (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects/safety and Equity). RESULTS: Six barriers to HIRAID implementation were identified by 670 respondents (response rate ~58%) representing all 30 sites: (i) lack of knowledge about HIRAID; (ii) high workload, (iii) lack of belief anything would change; (iv) not suitable for workplace; (v), uncertainty about what to do and (vi) lack of support or time for education. The three enablers were as follows: (i) willingness to learn and adopt something new; (ii) recognition of the need for something new and (iii) wanting to do what is best for patient care. The 10 corresponding domains were mapped to seven intervention functions, 21 behaviour change techniques and 45 mechanisms. The major components of the implementation strategy were a scaffolded education programme, clinical support and environmental modifications. CONCLUSIONS: A systematic process guided by the behaviour change wheel resulted in the generation of a multifaceted implementation strategy to implement HIRAID across rural, regional and metropolitan emergency departments. Implementation fidelity, reach and impact now require evaluation. IMPACT: HIRAID emergency nursing assessment framework reduced clinical deterioration relating to emergency care and improved self-confidence and documentation in emergency departments in pilot studies. Successful implementation of any intervention in the emergency department is notoriously difficult due to workload unpredictability, the undifferentiated nature of patients and high staff turnover. Key barriers and enablers were identified, and a successful implementation strategy was developed. This study uses theoretical frameworks to identify barriers and enablers to develop a data-driven, behavioural-focused implementation strategy to optimise the uptake of HIRAID in geographically diverse emergency departments which can be used to inform future implementation efforts involving emergency nurses. REPORTING METHOD: The CROSS reporting method (Supporting Information S3) was used to adhere to EQUATOR guidelines. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. TRIAL REGISTRATION: Australian New Zealand; Clinical Trials Registry (ANZCTR) number: ACTRN12621001456842, registered 25/10/2021.

Cardiac Output Directly Influences Intracardiac Air After Venous Air Embolism: An Echocardiographic Model Comparing Position Change on Intracardiac Air Bubble Clearance.

BACKGROUND AND OBJECTIVES: Venous air embolism (VAE) can cause significant morbidity and mortality. Prevention and management of VAE include cessation of air entrainment, positioning changes, and hemodynamic support. The degree to which position change and cardiac output (CO) moderate resolution of intracardiac air has not been rigorously studied using contemporary transesophageal echocardiography (TEE). METHODS: This observational cohort-type study aimed to identify the effect of supine vs sitting positioning on the movement and resolution of intracardiac air. In 20 patients undergoing seated neurosurgery, central venous air aspiration catheters were placed through the median basilic vein. TEE was used to estimate the time required for clearance of agitated microbubbles from the right atrium and ventricle in both the supine and sitting position. Estimates of CO were also obtained echocardiographically in each position. RESULTS: Average clearance time was faster in the sitting vs the supine position with no significant difference in CO. A negative correlation between CO and right atrial clearance time across all patients was demonstrated with a Pearson coefficient of -0.4 (95% CI -0.07, -0.65) with P = .02. CONCLUSION: During VAE, both patient position and CO can significantly affect how bubbles move through intracardiac chambers. However, augmenting CO during VAE may be clinically more feasible, efficient, and productive than changing positioning-especially during crises unless the changing in position is intended to halt the entrainment of air. Further TEE studies of intravascular air movement affected by other position changes (lateral, reverse Trendelenburg) and vasopressors should be considered.

Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic ß-oxidation from the metabolism of [D15]octanoate to deuterated water and detection with deuterium magnetic resonance methods. Perfused livers from a mouse model of MASLD reveal dysregulated hepatic ß-oxidation, findings that corroborate in vivo imaging. The high-fat-diet-induced MASLD mouse studies indicate that decreased ß-oxidative efficiency in the fatty liver could serve as an indicator of MASLD progression. Furthermore, our method provides a clinically translatable imaging approach for determining hepatic ß-oxidation efficiency.

Disparities in COVID-19 vaccine uptake, attitudes, and experiences between food system and non-food system essential workers.

The COVID-19 pandemic has disproportionately affected the health of food system (FS) essential workers compared with other essential and non-essential workers. Even greater disparity exists for workers in certain FS work settings and for certain FS worker subpopulations. We analyzed essential worker respondents (n = 151,789) in May-November 2021 data from the National Immunization Survey Adult COVID Module (NIS-ACM) to assess and characterize COVID-19 vaccination uptake (≥1 dose) and intent (reachable, reluctant), attitudes about COVID-19 and the vaccine, and experiences and difficulties getting the vaccine. We compared rates, overall and by certain characteristics, between workers of the same group, and between FS (n = 17,414) and non-food system (NFS) worker groups (n = 134,375), to determine if differences exist. FS worker groups were classified as "agriculture, forestry, fishing, or hunting" (AFFH; n = 2,730); "food manufacturing facility" (FMF; n = 3,495); and "food and beverage store" (FBS; n = 11,189). Compared with NFS workers, significantly lower percentages of FS workers reported ≥1 dose of COVID-19 vaccine or vaccine requirements at work or school, but overall vaccine experiences and difficulties among vaccinated FS workers were statistically similar to NFS workers. When we examined intent regarding COVID-19 vaccination among unvaccinated FS workers compared with NFS counterparts, we found a higher percentage of FMF and FBS workers were reachable whereas a higher percentage of AFFH workers were reluctant about vaccination, with differences by sociodemographic characteristics. Overall, results showed differences in uptake, intent, and attitudes between worker groups and by some sociodemographic characteristics. The findings reflect the diversity of FS workers and underscore the importance of collecting occupational data to assess health inequalities and of tailoring efforts to worker groups to improve confidence and uptake of vaccinations for infectious diseases such as COVID-19. The findings can inform future research, adult infectious disease interventions, and emergency management planning.

Laboratory Management of Mammalian Hosts for Ixodes scapularis -Host-Pathogen Interaction Studies.

Due to their hematophagous life cycle, hard-bodied ticks including the genus Ixodes are a potential vector for numerous pathogenic organisms including bacteria, protozoa, viruses, and infectious prions. The natural geographic range of several hard tick species, includig Ixodes scapularis, has expanded over recent decades. Consequently, there is an ongoing need to maintain, feed, and propagate ticks for host-pathogen interaction studies to better understand and mitigate their impact on human and animal health. Artificial membrane feeding of hard ticks has advanced in recent years, has study design advantages, and should be used, when possible, to reduce animal use, but it also has several limitations that require the continued use of mammalian hosts including mice, guinea pigs, and rabbits. In this overview, we discuss the best management practices for these relevant species with respect to biosafety, health, and optimal host comfort when used in studies that depend on tick feeding. The capsule-jacket method is preferred over the ear sock-E-collar method of tick feeding on rabbit hosts because of better host health, comfort, and increased study versatility.

Effect of different modalities of exercise on Fatty Liver Index in patients with metabolic syndrome: The RESOLVE randomized trial.

INTRODUCTION: Metabolic associated liver disease (MASLD) is the most common liver disease in the world especially in people with metabolic syndrome. First-line treatments mainly consist in lifestyle modifications for these populations. The main objective of this study is to assess the effect of a short intervention program with different exercise modalities on Fatty Liver Index (FLI) in patients with metabolic syndrome. METHODS: 85 patients (40 men, 45 women) with metabolic syndrome and liver steatosis were randomized in 3 groups for a 3 weeks residential program: Re group-high-resistance-moderate-endurance; rE group-moderate-resistance with high-endurance and re group-moderate-resistance with moderate-endurance. Patients also followed a negative energy balance of 500 kcal/day. Then, a follow-up of 1 year with interviews with dieticians and exercise physicians to maintain lifestyle modification was performed. Anthropometric, cardiometabolic and hepatic outcomes were performed at baseline, at the end of the 3-week residential program, 3 months, 6 months and 12 months after baseline. RESULTS: This study demonstrated that all three training programs significantly improve FLI and that this effect was lasting among the follow-up (p < 0.001). More specifically, the Re group exhibited a more pronounced decrease in FLI compared with re (p < 0.05). Finally, the decrease in FLI was associated with improvement in anthropometric and cardiometabolic outcomes at 3-weeks (p < 0.001) and 3-months (p < 0.01). CONCLUSION: Short duration program is effective to improve FLI and cardiometabolic parameters in MASLD patients. Encourage to increase physical activity even for a short duration is relevant in this population.

Measuring episodic memory and mental time travel: crossing the species gap.

Mental time travel is the projection of the mind into the past or future, and relates to experiential aspects of episodic memory, and episodic future thinking. Framing episodic memory and future thinking in this way causes a challenge when studying memory in animals, where demonstration of this mental projection is prevented by the absence of language. However, there is good evidence that non-human animals pass tests of episodic memory that are based on behavioural criteria, meaning a better understanding needs to be had of the relationship between episodic memory and mental time travel. We argue that mental time travel and episodic memory are not synonymous, and that mental time travel is neither a requirement of, nor an irrelevance to, episodic memory. Mental time travel can allow improved behavioural choices based on episodic memory, and work in all species (including humans) should include careful consideration of the behavioural outputs being measured. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Adaptive-Driven CT Simulation-Free Soft Tissue Stereotactic Body Radiation Therapy: A Single-Patient Case Report.

Online adaptive radiotherapy (ART) enables accommodation for variations in patient setup and anatomical changes, allowing for fractional replanning for target coverage, organ at risk (OAR) sparing, and application of CT simulation-free (SF) workflows. SF workflows bypass the conventional simulation CT scan at the potential trade-off in dosimetric uncertainty. ART can alleviate many of these uncertainties, and this work extends previous experience with an Ethos adaptive cone-beam computed tomography (CBCT)-based SF process to treating a unique bony and soft tissue case with stereotactic body radiation therapy (SBRT). The patient is an 83-year-old male with metastatic prostate cancer, presenting with metastases near the right posterior ischium and a right perirectal lymph node. The patient's history includes multiple radiation treatments and androgen deprivation therapy (ADT). Rising prostate-specific antigen(PSA) levels and new metastases identified via positron emission tomography (PET)/CT prostate-specific membrane antigen (PSMA) led to SBRT re-irradiation, considered safe due to the time lapse since previous treatments. Using a HyperSight-equipped Ethos ART system, an SF SBRT workflow utilized the patient's recent PET/CT images for target and OAR delineation. A nine-field adaptive intensity-modulated radiotherapy(IMRT) treatment plan was generated to deliver 3600 Gy in three fractions with a primary focus to limit the dose to proximal OARs and the previously treated region. At the adaptive treatment, the patient is positioned based on anatomical marks, and axial images from HyperSight CBCT are used to contour the OARs and targets. These modified contours accommodate daily variations and are used to recalculate the reference plan and generate a new adapted plan. The adapted plan is selected if coverage improvement and OAR sparing are achieved. For each newly adapted plan, Ethos-generated synthetic CT is reviewed prior to treatment to verify no errors occurred in the deformable propagation between the reference image and the fractional CBCT. For this patient, the adapted plan was selected for all fractions due to improved target coverage, particularly of the soft tissue target, and OAR sparing. The patient tolerated the treatment well and demonstrated a good response on three-month follow-up PSMA PET/CT imaging. This case highlights the efficacy of CBCT-driven SF ART in complex re-irradiation scenario. Future enhancements in the Ethos treatment planning system, including direct dose computation on HyperSight CBCT images, will streamline SF workflows and expand their applicability. Careful consideration of potential on-unit OAR changes and target motion remains crucial for successful SF ART applications.

Comparison of the Vaginal and Labial Dimensions of Ethnic Chinese and Western Nullipara.

INTRODUCTION AND HYPOTHESIS: Vaginal dimensions have clinical and surgical implications. We sought to quantify the differences between vaginal and labial dimensions in healthy ethnic Chinese and Western women with normal pelvic organ support. METHODS: This is a cross-sectional study of a convenience sample of ethnic Chinese nulliparas (n = 33) and Western nulliparas (n = 33) recruited for research purposes. For each subject, magnetic resonance imaging was used to quantify the vaginal and labial dimensions. Specifically, we identified the anterior and posterior vaginal wall, the outline of the cervix in the mid-sagittal and coronal planes, and the distance from the labia majora to the hymenal ring at the urethral meatus. RESULTS: There were significant differences in age and weight between groups. Substantial variation in vaginal and labial dimensions was found within each group. The vaginal and labial dimensions of ethnic Chinese women ranged from 9-21% smaller than those of Western women; In the ethnic Chinese group, increasing weight and BMI correlated with greater labial distance (r = 0.66 and r = 0.63 respectively); as did height and the distance from the vaginal opening to the cervical os (r = 0.5). In the Western group, only weight correlated with the labial distance (r = 0.51). CONCLUSIONS: Significant group differences in vaginal and labial dimensions were found, with the dimensions of Chinese nulliparas being up to 21% smaller than those of Western nulliparas.

Cefepime-taniborbactam activity against antimicrobial-resistant clinical isolates of Enterobacterales and Pseudomonas aeruginosa: GEARS global surveillance programme 2018-22.

OBJECTIVES: Taniborbactam is a boronate-based ß-lactamase inhibitor in clinical development in combination with cefepime. METHODS: Cefepime-taniborbactam and comparator broth microdilution MICs were determined for patient isolates of Enterobacterales (n = 20 725) and Pseudomonas aeruginosa (n = 7919) collected in 59 countries from 2018 to 2022. Taniborbactam was tested at a fixed concentration of 4 mg/L. Isolates with cefepime-taniborbactam MICs ≥ 16 mg/L underwent WGS. ß-Lactamase genes were identified in additional meropenem-resistant isolates by PCR/Sanger sequencing. RESULTS: Taniborbactam reduced the cefepime MIC90 value for all Enterobacterales from >16 to 0.25 mg/L (>64-fold). At ≤16 mg/L, cefepime-taniborbactam inhibited 99.5% of all Enterobacterales isolates; >95% of isolates with MDR and ceftolozane-tazobactam-resistant phenotypes;  ≥ 89% of isolates with meropenem-resistant and difficult-to-treat-resistant (DTR) phenotypes; >80% of isolates with meropenem-vaborbactam-resistant and ceftazidime-avibactam-resistant phenotypes; 100% of KPC-positive, 99% of OXA-48-like-positive, 99% of ESBL-positive, 97% of acquired AmpC-positive, 95% of VIM-positive and 76% of NDM-positive isolates. Against P. aeruginosa, taniborbactam reduced the cefepime MIC90 value from 32 to 8 mg/L (4-fold). At ≤16 mg/L, cefepime-taniborbactam inhibited 96.5% of all P. aeruginosa isolates; 85% of meropenem-resistant phenotype isolates; 80% of isolates with MDR and meropenem-vaborbactam-resistant phenotypes; >70% of isolates with DTR, ceftazidime-avibactam-resistant and ceftolozane-tazobactam-resistant phenotypes; and 82% of VIM-positive isolates. Multiple potential mechanisms of resistance, including carriage of IMP, or alterations in PBP3 (ftsI), porins (decreased permeability) and efflux (up-regulation) were present in most isolates with cefepime-taniborbactam MICs ≥ 16 mg/L. CONCLUSIONS: Cefepime-taniborbactam exhibited potent in vitro activity against Enterobacterales and P. aeruginosa, and inhibited most carbapenem-resistant isolates, including those carrying serine carbapenemases or NDM/VIM MBLs.

Artificial intelligence for contrast-enhanced ultrasound of the liver: a systematic review.

Introduction The research field of Artificial intelligence (AI) in medicine and especially in gastroenterology is rapidly progressing with the first AI tools entering routine clinical practice, for example in colorectal cancer screening. Contrast-enhanced ultrasound (CEUS) is a highly reliable, low-risk and low-cost diagnostic modality for the examination of the liver. However, doctors need many years of training and experience to master this technique and, despite all efforts to standardize CEUS, it is often believed to contain significant interrater variability. As has been shown for endoscopy, AI holds promise to support examiners at all training levels in their decision-making and efficiency. Methods In this systematic review, we analyzed and compared original research studies applying AI methods to CEUS examinations of the liver published between January 2010 and February 2024. We performed a structured literature search on PubMed, Web of Science and IEEE. Two independent reviewers screened the articles and subsequently extracted relevant methodological features, e.g. cohort size, validation process, machine learning algorithm used, as well as indicative performance measures from the included articles. Results We included 41 studies with most applying AI methods for classification tasks related to focal liver lesions. These included distinguishing benign vs. malignant or classifying the entity itself, while a few studies tried to classify tumor grading, microvascular invasion status or response to transcatheter arterial chemoembolization directly from CEUS. Some articles tried to segment or detect focal liver lesions, while others aimed to predict survival and recurrence after ablation. The majority (25/41) of studies used hand-picked and/or annotated images as data input to their models. We observed mostly good to high reported model performances with accuracies ranging between 58.6% and 98.9%, while noticing a general lack of external validation. Conclusion Even though multiple proof-of-concept studies for the application of AI methods to CEUS examinations of the liver exist and report high performance, more prospective, externally validated and multicenter research is needed to bring such algorithms from desk to bedside.