Prospective, Randomized Comparative Evaluation of a Novel Hands-On Endourology Training Curriculum.

INTRODUCTION: The aim of this randomised prospective trial was to evaluate a novel hands-on endourological training programme (HTP) and compare it to the standard endourological colloquium (SC). METHODS: A new HTP was created based on a sequence of theoretical, video-based, and practical elements emphasising contemporary teaching methods. An existing SC in which live endourological operations were attended served as a comparison. Medical students were enrolled in a ratio of 1:2 (SC:HTP). Objective knowledge questionnaires (5 questions, open answers) and subjective Likert-type questionnaires (rating 1-3 vs. 4-5) were used for evaluation. Primary endpoint was urological knowledge transfer; secondary endpoints were learning effects, progression, and urological interest. RESULTS: 167 students (SC n = 52, HTP n = 115) were included. The knowledge assessment showed a significant increase in knowledge transfer benefitting the HTP on all 5 surveyed items (mean: n = 4/5/4/3/2 vs. n = 2/3/1/1, p < 0.0001). Interest and duration of the course were rated significantly more positively by HTP students (100.0/95.0% vs. 85.0/70.0%, p < 0.0001). The HTP students were significantly more confident in performing a cystoscopy independently (HTP 43.5% vs. SC 11.5%, p < 0.0001) and significantly claimed more often to have gained interdisciplinary and urological skills during the course (HTP 90.0/96.5% vs. SC 23.1/82.7%, p < 0.0001/p = 0.003). HTP students were also more likely to take the course again (HTP 98.2% vs. SC 59.6%, p < 0.0001). CONCLUSION: Modifying endourological teaching towards hands-on teaching resulted in stronger course interest, greater confidence regarding endourologic procedures, and significantly increased urologic knowledge transfer.

Feasibility, acceptance, safety, and effectiveness of antibiotic therapy as alternative treatment approach to appendectomy in uncomplicated acute appendicitis.

PURPOSE: Based on results from randomized controlled trials, there is an increasing discussion if antibiotic treatment is an equivalent therapeutic approach to appendectomy in uncomplicated acute appendicitis. This observational prospective study evaluates its feasibility, safety, and effectiveness in clinical practice. METHODS: The study included all consecutive adults treated for acute appendicitis over an 18-month period in one hospital. Patients receiving antibiotics were compared to those treated surgically. Follow-up comprised 1 year. The primary endpoint was treatment success, defined as no secondary appendectomy during follow-up (antibiotic group) or successful appendectomy (primary surgical group). Secondary endpoints were complications, duration of hospital stay, pain intensity, and length of absence from work. RESULTS: 54/124 (43.6%) patients were primarily treated with antibiotics and 70/124 (56.4%) surgically. Treatment success at 1 year was 77.1% (95%-CI 62.8-88%) for antibiotic and 100% for surgical treatment. Complications were non-significantly less frequent both among all patients treated with antibiotics and among patients undergoing secondary appendectomy compared to patients undergoing primary appendectomy (20.8% vs. 27.1% and 9.1% vs. 27.1%). The initial hospital stay was significantly shorter in the antibiotic group (mean 3.6 vs. 4.8 days, median 3 days, p = 0.03). After 1 year, the cumulative hospital stay was not different between groups. CONCLUSIONS: Appendectomy remains the most effective treatment for the definitive cure of acute appendicitis. However, antibiotic therapy can be a safe alternative approach for selected patients with uncomplicated acute appendicitis. TRIAL REGISTRATION: DRKS00010401.

A second combinatorial immune receptor in monocytes/macrophages is based on the TCRγδ.

Recent evidence indicates that monocytes and macrophages express T cell receptor (TCR)αß-like combinatorial immune receptors. Here, we demonstrate the presence of a second recombinatorial immunoreceptor, which is structurally based on the TCR γ- and δ-chains, in human and murine monocytes and differentially activated macrophages (referred to here as TCRL(m)γδ). In vitro, infection of macrophages with mycobacteria and gram positive or gram negative bacteria induced expression of donor-specific and differential TCRL(m)Vδ repertoires indicating that the novel immunoreceptor represents a dynamic flexible host defense system that responds to bacterial challenge. In vivo, we find that TCRL(m)γδ bearing macrophages, which express highly restricted repertoires of the antigen-binding Vδ chain, accumulate in the cerebrospinal fluid in acute bacterial meningitis and in advanced lesions of atherosclerosis. These results identify an as yet unrecognized monocyte/macrophage subpopulation that bears combinatorial TCRL(m)γδ immune receptors, and is associated with both acute and chronic inflammatory diseases. Moreover, they indicate that the monocytic lineage uses the same bipartite system of TCRαß/TCRγδ-based combinatorial immune receptors that is present in T cells. Our findings suggest specific roles of monocytes/macrophages in various inflammatory conditions and lend further evidence that flexible immune recognition in higher vertebrates operates on a broader cellular basis than previously thought.

The neutrophil recombinatorial TCR-like immune receptor is expressed across the entire human life span but repertoire diversity declines in old age.

Recent evidence has revealed the existence of T cell receptor (TCR) αß-based recombinatorial immune receptors in phagocytes. Here, we performed a systematic survey of the variable ß-chain repertoires of the neutrophil TCR-like αß immunoreceptor (referred to as TCRL(n)αß) in defined cohorts of young and old individuals. Peripheral blood CD15(+) neutrophils from young adults (age 30 ± 7 years, n=12) expressed an average number of 13 ± 6 distinct TCRL(n) Vß-chains from the total pool of 25 human Vß-chains. Neutrophils from aged subjects (age 76 ± 6 years, n=12) also consitutively express the TCRL(n), however, only a small number of Vß-chains is used (4 ± 2). Consistent with this, the average number of expressed CDR3 Vß length variants was fourfold higher in young individuals than in aged subjects (33 ± 24 vs. 8 ± 3). Young adults showed broad usage of all TCRL(n) Vß-chains. In contrast, >70years individuals displayed a striking repertoire polarization towards the TCRL(n) Vß1 and Vß5b chains and a high degree of Vß5b clonotype sharing. Our study reveals broad TCRL(n) repertoire diversity in young adults and demonstrates that the neutrophil variable immune receptor is expressed throughout the entire human life span. The marked decline in TCRL(n) repertoire diversity in old age identifies a novel mechanism of immunosenescence in neutrophils.