Impact of urinary catheter on resistance patterns and clinical outcomes on complicated urinary tract infection.

INTRODUCTION AND HYPOTHESIS: Complicated urinary tract infection (cUTI) is highly prevalent and costly for health systems. The impact of the indwelling urinary catheter on etiologic agents and clinical outcomes has been poorly studied in Latin America. METHODS: Cross-sectional study including patients with cUTI, with positive urine culture, treated at Hospital Universitario San Ignacio, Bogotá (Colombia) between 2017 and 2020. Clinical and microbiologic characteristics, treatments and outcomes are explored, comparing those with and without indwelling urinary catheter. RESULTS: Seven hundred thirty-five patients with non-catheter-associated cUTI (NC-cUTI) and 165 with catheter-associated cUTI (CAUTI) were included. CAUTI group had a higher proportion of recurrent UTI (18% vs 33.3%, p < 0.001), ICU requirement (2.7% vs 8.5%, p < 0.001), longer hospital stay (6 vs 10 days, p < 0.001) and > 30 days unplanned readmission rate (5.8% vs 10.3%, p < 0.001). In the same group, we found a higher frequency of Pseudomonas spp (2.6% vs 9.4%, p < 0.001), Enterococcus spp. (2.4% vs 3.3%, p = 0.016), Serratia marcescens (0.6% vs 3.3%, p < 0.001) and Citrobacter freundii (0.5% vs 5.7%, p < 0.001). It implied a higher number of patients treated with fourth-generation cephalosporins (1.4% vs 4.8%, p = 0.004), ertapenem (32.9% vs 41.8%, p = 0.027) and carbapenems associated with a second antibiotic (1.9% vs 8.5%, p < 0.001). CONCLUSIONS: Patients with CAUTI have a higher frequency of resistant germs, require greater use of resources and have worse clinical outcomes than patients who do not require such devices. Measures should be strengthened to minimize its use, in both the hospital and outpatient setting.

Novel Cre-Expressing Mouse Strains Permitting to Selectively Track and Edit Type 1 Conventional Dendritic Cells Facilitate Disentangling Their Complexity in vivo.

Type 1 conventional DCs (cDC1) excel in the cross-priming of CD8+ T cells, which is crucial for orchestrating efficient immune responses against viruses or tumors. However, our understanding of their physiological functions and molecular regulation has been limited by the lack of proper mutant mouse models allowing their conditional genetic targeting. Because the Xcr1 and A530099j19rik (Karma/Gpr141b) genes belong to the core transcriptomic fingerprint of mouse cDC1, we used them to engineer two novel Cre-driver lines, the Xcr1Cre and KarmaCre mice, by knocking in an IRES-Cre expression cassette into their 3'-UTR. We used genetic tracing to characterize the specificity and efficiency of these new models in several lymphoid and non-lymphoid tissues, and compared them to the Clec9aCre mouse model, which targets the immediate precursors of cDCs. Amongst the three Cre-driver mouse models examined, the Xcr1Cre model was the most efficient and specific for the fate mapping of all cDC1, regardless of the tissues examined. The KarmaCre model was rather specific for cDC1 when compared with the Clec9aCre mouse, but less efficient than the Xcr1Cre model. Unexpectedly, the Xcr1Cre model targeted a small fraction of CD4+ T cells, and the KarmaCre model a significant proportion of mast cells in the skin. Importantly, the targeting specificity of these two mouse models was not changed upon inflammation. A high frequency of germline recombination was observed solely in the Xcr1Cre mouse model when both the Cre and the floxed alleles were brought by the same gamete irrespective of its gender. Xcr1, Karma, and Clec9a being differentially expressed within the cDC1 population, the three CRE-driver lines examined showed distinct recombination patterns in cDC1 phenotypic subsets. This advances our understanding of cDC1 subset heterogeneity and the differentiation trajectory of these cells. Therefore, to the best of our knowledge, upon informed use, the Xcr1Cre and KarmaCre mouse models represent the best tools currently reported to specifically and faithfully target cDC1 in vivo, both at steady state and upon inflammation. Future use of these mutant mouse models will undoubtedly boost our understanding of the biology of cDC1.

Development of an interprofessional lean facilitator assessment scale.

High reliability is important for optimising quality and safety in healthcare organisations. Reliability efforts include interprofessional collaborative practice (IPCP) and Lean quality/process improvement strategies, which require skilful facilitation. Currently, no validated Lean facilitator assessment tool for interprofessional collaboration exists. This article describes the development and pilot evaluation of such a tool; the Interprofessional Lean Facilitator Assessment Scale (ILFAS), which measures both technical and 'soft' skills, which have not been measured in other instruments. The ILFAS was developed using methodologies and principles from Lean/Shingo, IPCP, metacognition research and Bloom's Taxonomy of Learning Domains. A panel of experts confirmed the initial face validity of the instrument. Researchers independently assessed five facilitators, during six Lean sessions. Analysis included quantitative evaluation of rater agreement. Overall inter-rater agreement of the assessment of facilitator performance was high (92%), and discrepancies in the agreement statistics were analysed. Face and content validity were further established, and usability was evaluated, through primary stakeholder post-pilot feedback, uncovering minor concerns, leading to tool revision. The ILFAS appears comprehensive in the assessment of facilitator knowledge, skills, abilities, and may be useful in the discrimination between facilitators of different skill levels. Further study is needed to explore instrument performance and validity.

Evaluación de la relación entre el habito y frecuencia del consumo de lácteos y el nivel de calcio presente en la orina de jóvenes universitarios de la ciudad de Armenia / Evaluation of the relationship between the habit and frequency of consumption of milk and calcium this level in urine of college students of the city of Armenia

La presente investigación evaluó los estilos de vida de jóvenes universitarios,en este caso la relación entre el hábito y frecuencia del consumo de lácteosy nivel de calcio presente en la orina de jóvenes entre los 18 y 25 años de laciudad de Armenia. Se realizó un estudio exploratorio descriptivo, en 98jóvenes a los cuales se les aplico un instrumento de valoración donde seobtuvo información acerca de sus estilos de vida, consumo de lácteos, y seles práctico un examen de calcio en orina ocasional. Los resultados obtenidos arrojaron que toda la población objeto de estudio consumen productos lácteos, los hombres prefieren consumir más la leche con un 60% que las mujeres con un 51%. No se encontró correlación entre el consumo de lácteos y la cantidad de calcio presente en la Orina dado que los valores dieron muy cercanos a cero (-0,0288035 - 0,12558183). No se evidenció correlación entre el consumo, frecuencia y tipo de producto lácteo consumido vs. cantidad de calcio encontrada en la orina y la alteración de los niveles de calcio en orina que darían origen al padecimiento de hipercalciuria o hipocalciuria, por lo cual es necesario buscar y correlacionar otras fuentes de calcio que eviten los padecimientos anteriormente mencionados...

XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses.

Naive CD8(+) T cell priming during tumor development or many primary infections requires cross-presentation by XCR1(+) dendritic cells (DCs). Memory CD8(+) T lymphocytes (mCTLs) harbor a lower activation threshold as compared with naive cells. However, whether their recall responses depend on XCR1(+) DCs is unknown. By using a new mouse model allowing fluorescent tracking and conditional depletion of XCR1(+) DCs, we demonstrate a differential requirement of these cells for mCTL recall during secondary infections by different pathogens. XCR1(+) DCs were instrumental to promote this function upon secondary challenges with Listeria monocytogenes, vesicular stomatitis virus, or Vaccinia virus, but dispensable in the case of mouse cytomegalovirus. We deciphered how XCR1(+) DCs promote mCTL recall upon secondary infections with Listeria. By visualizing for the first time the in vivo choreography of XCR1(+) DCs, NK cells and mCTLs during secondary immune responses, and by neutralizing in vivo candidate molecules, we demonstrate that, very early after infection, mCTLs are activated, and attracted in a CXCR3-dependent manner, by NK cell-boosted, IL-12-, and CXCL9-producing XCR1(+) DCs. Hence, depending on the infectious agent, strong recall of mCTLs during secondary challenges can require cytokine- and chemokine-dependent cross-talk with XCR1(+) DCs and NK cells.

Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells.

Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.

TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8α+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques.

In mice, CD8α(+) myeloid dendritic cells (mDC) optimally cross-present Ags to CD8(+) T cells and respond strongly to TLR3 ligands. Although equivalent DC have been identified by comparative genomic analysis and functional studies in humans as XCR1(+)CD141 (BDCA-3)(+)Clec9A(+)cell adhesion molecule 1(+) mDC, and in sheep as CD26(+) mDC, these cells remained elusive in nonhuman primates. To remedy this situation, we delineated precisely DC and monocyte populations by 12-color flow cytometry and transcriptomic analyses in healthy rhesus macaques. We identified a new mDC population, with strong phenotypic and transcriptional homology to human CD141(+) and murine CD8α(+) mDC, including XCR1 membrane expression as a conserved specific marker. In contrast, high CD11c expression was not characteristic of mDC in macaques, but of CD16(+) monocytes. Like their human and murine homologs, simian XCR1(+) mDC had much stronger responses to TLR3 stimulation than other myeloid cells. The importance of this new mDC population was tested in SIV(mac251) infection, the most relevant animal model for pathogenic HIV-1 infection and vaccination. This population increased sharply and transiently during acute infection, but was reduced in blood and spleen during advanced disease. The identification of XCR1(+) mDC in rhesus macaques opens new avenues for future preclinical vaccinal studies and highlights XCR1 as a prime candidate for targeted vaccine delivery.

Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin.

In the skin, the lack of markers permitting the unambiguous identification of macrophages and of conventional and monocyte-derived dendritic cells (DCs) complicates understanding of their contribution to skin integrity and to immune responses. By combining CD64 and CCR2 staining, we successfully identified each of these cell types and studied their origin, transcriptomic signatures, and migratory and T cell stimulatory properties. We also analyzed the impact of microbiota on their development and their contribution to skin inflammation during contact hypersensitivity. Dermal macrophages had a unique scavenging role and were unable to migrate and activate T cells. Conventional dermal DCs excelled both at migrating and activating T cells. In the steady-state dermis, monocyte-derived DCs are continuously generated by extravasated Ly-6C(hi) monocytes. Their T cell stimulatory capacity combined with their poor migratory ability made them particularly suited to activate skin-tropic T cells. Therefore, a high degree of functional specialization occurs among the mononuclear phagocytes of the skin.