Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

Protective function of sclerosing cholangitis on IBD.

OBJECTIVE: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism. DESIGN: Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3+ Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction. RESULTS: We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3+ Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3+ Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3+ expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis. CONCLUSION: This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.

Shaping ultrasound in midwifery: towards an evidence-based training framework for enhanced prenatal care.

BACKGROUND: Academic advancement of the midwifery profession highlights the need to establish standardized qualifications in obstetric ultrasound diagnosis, being a central part of prenatal care. Thus, introduction of an evidence-based training program is warranted. We aimed to reviewed curriculum designs used in midwifery ultrasound education. METHODS: A systematic literature research was conducted. Embase, PubMed and Google Scholar database was reviewed for publications using the terms "[midwife], [midwives], [midwifery students], [obstetric ultrasound], [midwife sonographer] and [education], [teaching], [program], [course], [curriculum] and [learning]". Papers with full description of curriculum designs or educational programs on obstetrical ultrasound for midwives were included and scrutinized against pre-defined criteria according to the PICO (Population, Intervention, Comparator, Outcomes) scheme. RESULTS: 29 publications were included. Studies demonstrated a significant disparity according to course concepts being used. Differing parameters included: Duration, structure, learning approaches, course content, examination concepts and target groups (practising midwives vs. midwives in education). CONCLUSION: An evidence-based ultrasound educational program for midwives remains to be developed, including further educational guidelines. Clinical applications by midwives, as well as the distinctions from medical practise, particularly in terms of legal considerations, needs to be defined.

Enhancing ultrasound education in obstetrics and gynecology in Germany: insights and innovations from postgraduate training.

BACKGROUND: Ultrasound (US) has become integral to obstetrics and gynecology (Ob/Gyn), necessitating proficient training during residency. Despite its clinical importance, there is a perceived gap in the quality and structure of postgraduate ultrasound education in Germany. METHODS: A cross-sectional survey was conducted among Ob/Gyn residents in Germany from October 2023 to March 2024, using the LimeSurvey platform. The survey, distributed via email, social media, and physical flyers, garnered 211 participants, with 115 completing all sections. The questionnaire covered demographic details, US training experiences, and the perceived importance of US in clinical practice. RESULTS: Although US was highly valued by respondents, with an average of 26.1% of their clinical activity devoted to it, there was significant dissatisfaction with the training quality. Key issues included inadequate supervision, the necessity of self-training, and low participation in certification courses. Despite 93.0% awareness of professional US organizations like the German Society for Ultrasound in Medicine (DEGUM), engagement with structured training programs was minimal. DISCUSSION: The study highlights a critical need for standardized US training protocols and curricular reform in Ob/Gyn residencies in Germany. The discrepancy between the recognized importance of US and the quality of training indicates a pressing need for improvements. Addressing these gaps through comprehensive, structured educational reforms could significantly enhance the proficiency and confidence of future Ob/Gyn specialists, ultimately improving patient care.

First insights of integrating the Bonn Internship Curriculum for Point-of-Care Ultrasound (BI-POCUS): progress and educational aspects.

BACKGROUND: Point-of-care ultrasound (POCUS) is rapidly gaining prominence in various clinical settings. As its use becomes more widespread, there is a growing need for comprehensive ultrasound training in medical education to ensure that future healthcare professionals are proficient in this essential diagnostic tool. OBJECTIVE: This study is the first attempt by the University of Bonn to seamlessly integrate ultrasound courses and the use of ultrasound devices into the regular activities of final year medical students and to evaluate the usage of these devices. METHODS: A total of forty students in their practical year were provided with a hendheld ultrasound device for a period of four months. During this time, they were invited to take part in eight optional ultrasound courses in which they acquired images and those images were rated using a specially developed rating system. At the end of the tertial, students were able to take part in a voluntary survey on the use of the equipment. RESULTS: Participation in the optional ultrasound courses was well received, with the Introduction and FAST module drawing the largest number of participants (29). Among the ultrasound images acquired by students, those of the lungs obtaining the highest rating, with 18.82 (SD ± 4.30) points out of 23 points, while the aorta and vena cava images scored lowest, with an average of 16.62 (SD ± 1.55) points. The overall mean score for all images was 17.47 (SD ± 2.74). Only 21 students responded to the survey. Of the participating students, 67% used the device independently four times or fewer during the tertial. CONCLUSION: The study aimed to enhance the BI-POCUS curriculum by improving students' ultrasound skills during their practical year. However, device usage was lower than expected, with most students using it only once a month or less. This raises concerns about the justification of the effort and resources. Future initiatives will focus on technical improvements, better login data provision, and closer monitoring of usage and progress, emphasizing the need for practical ultrasound training in medical education.

A four year follow-up survey on the teledidactic TELUS ultrasound course: long-term benefits and implications.

BACKGROUND: The COVID-19 pandemic disrupted traditional medical education, prompting innovative teaching methods for practical skills training. The teledidactic TELUS ultrasound course, launched in 2020-2021, aimed to provide remote instruction in ultrasound techniques. OBJECTIVE: This study assesses the long-term impact of the teledidactic ultrasound course conducted during the study years on current clinical practice. METHODS: In 2024, a follow-up survey was conducted with former TELUS course students now practicing as physicians across various specialities. Participants rated their confidence in ultrasound examinations and its frequency in practice. RESULTS: 21 out of 30 participants (70%) completed the survey. 71.4% rated the course experience as excellent (5/5 points). Most reported significant learning gains, especially in the FAST module. While all agreed the course enhanced their ultrasound skills, its impact on patient care received mixed reviews. Frequency of ultrasound use varied widely among specialities, with high use in surgery and internal medicine but less in psychiatry, neurology, and ophthalmology. Notably, 42,9% had not pursued further ultrasound training post-course. CONCLUSION: The teledidactic ultrasound course effectively provided remote education, integrating skills into practice. Mixed reviews on patient care impact and speciality-specific ultrasound use suggest sustained integration depends on relevance and ongoing education. Self-assessment results support online ultrasound courses, indicating potential use in resource-limited or geographically constrained settings.

Applications of Point-of-Care-Ultrasound in Neonatology: A Systematic Review of the Literature.

Point-of-care ultrasound (POCUS) integration into neonatology offers transformative potential for diagnostics and treatment, enhancing immediacy and precision of clinical decision-making in this vulnerable patient population. This systematic review aims to synthesize evidence on POCUS applications, benefits, challenges, and educational strategies in neonatology. Literature search was conducted using SPIDER scheme keywords and MeSH terms related to POCUS and neonatology. Studies focusing on POCUS applications, its impact on clinical outcomes, and educational interventions for skill acquisition were included and analyzed using standardized tools, followed by a narrative synthesis of the findings. The search yielded 68 relevant publications, encompassing original research, reviews, and guidelines. POCUS applications varied across cardiovascular, pulmonary, neurological, and abdominal assessments. Key benefits included a reduced need for invasive procedures and rapid bedside diagnosis. Challenges included steep learning curves for clinicians and the need for standardized training and guidelines. Educational strategies highlighted the effectiveness of simulation-based training in enhancing ultrasound proficiency among neonatal care providers. POCUS represents a significant advancement in neonatal medicine, offering benefits for patient care. Addressing identified challenges through comprehensive training programs and developing standardized guidelines is crucial for optimized use. Future research should focus on evaluating educational outcomes and long-term impacts of POCUS integration into neonatal care.

A Gradient of Intestinal Inflammation in Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease associated with inflammatory bowel disease (IBD). The percentage of PSC patients diagnosed with concomitant IBD varies considerably between studies. This raises the question whether all PSC patients would show intestinal inflammation if screened thoroughly, even in the absence of symptoms. METHODS: To address this question, we collected intestinal biopsies of healthy controls (n = 34), PSC (n = 25), PSC-IBD (n = 41), and IBD (n = 51) patients in a cross-sectional study and carried out cytokine expression profiling, 16S sequencing, in-depth histology, and endoscopy scoring. RESULTS: We found that the vast majority of PSC patients even without clinically manifest IBD showed infiltration of immune cells and increased expression of IL17A and IFNG in intestinal biopsies. However, expression of IL10 and FOXP3 were likewise increased, which may explain why these PSC patients have intestinal inflammation only on a molecular level. This subclinical inflammation in PSC patients was focused in the distal colon, whereas PSC-IBD patients showed inflammation either at the distal colon or on the right side of the colon and the terminal ileum. Furthermore, we observed that PSC patients without IBD showed signs of dysbiosis and exhibited a distinct microbial profile compared with healthy controls. CONCLUSIONS: We found a gradient of intestinal inflammation in the vast majority of PSC patients even in the absence of IBD. Thus, further studies evaluating the effect of anti-inflammatory therapies in PSC patients and their impact on the emergence of clinically manifest IBD and colorectal cancer development are needed.