SummaryDendritic cells (DCs) are professional antigen-presenting cells that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues and species to analyze their function in the absence of macrophage contamination. Here, we provide and validate a universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues. The use of a minimal set of lineage-imprinted markers was sufficient to subdivide DCs into conventional type 1 (cDC1s), conventional type 2 (cDC2s), and plasmacytoid DCs (pDCs) across tissues and species. This way, a large number of additional markers can still be used to further characterize the heterogeneity of DCs across tissues and during inflammation. This framework represents the way forward to a universal, high-throughput, and standardized analysis of DC populations from mutant mice and human patients.

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

More infections were caused by non-albicans than Candida albicans strains. The majority of patients were treated only after diagnostic confirmation, rather than empirically. First-line antifungal susceptibility was associated with lower mortality.

No abstract

We evaluated the impact of a prospective audit and feedback antimicrobial stewardship program (ASP) on antibiotic prescription and resistance trends in a hematology-oncology unit in a university hospital (National University Cancer Institute, Singapore [NCIS]). A prospective interrupted time-series study comprising 11-month pre-intervention (PIP) and intervention evaluation phases (IEP) flanking a one-month implementation phase was carried out. Outcome measures included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and all antibiotics (encompassing audited and non-audited antibiotics), and the incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital. There were 580 ASP recommendations from 1,276 audits, with a mean monthly compliance of 86.9%. Significant reversal of prescription trends towards reduced prescription of audited (coefficient = -2.621; 95% confidence interval [CI]: -4.923, -0.319; p = 0.026) and all evaluated antibiotics (coefficient = -4.069; 95% CI: -8.075, -0.063; p = 0.046) was observed. No changes were seen for both internal and external controls, except for the reversal of prescription trends for cephalosporins hospital-wide. Antimicrobial resistance did not change over the time period of the study. Adverse outcomes-the majority unavoidable-occurred following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be implemented in the complex setting of hematology-oncology inpatients.

No abstract

Background: Anastomotic leakage after a colorectal resection results in devastating consequences for patients. Indocyanine green fluorescence angiography is a modality to visualize vascular perfusion at the anastomotic site and can help surgeons decide the viability of the anastomosis. We performed this systematic review and meta-analysis to evaluate the efficacy of indocyanine green fluorescence angiography in decreasing anastomotic leakage. Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched to identify studies comparing the use of indocyanine green fluorescence angiography versus standard care on rates of anastomotic leakage. Data were pooled with the Mantel-Haenszel method and analyzed based on a random-effects model to estimate the pooled odds ratio and 95% confidence interval. The heterogeneity of studies was evaluated using I 2 statistic. Results: Twenty studies were included in this meta-analysis of 5,498 patients. The pooled estimate of the odds ratio was 0.46 (95% confidence interval 0.34e0.62; P < .00001) favoring indocyanine green fluorescence angiography. The overall anastomotic leak rate was 3.7% (n ¼ 82) in the intervention group and 8.6% (n ¼ 282) in the control group. Indocyanine green fluorescence angiography led to a change in the anastomotic site in 216 (9.7%) patients. Subgroup analyses of anastomotic leakage requiring intervention, patients requiring a low colorectal anastomosis, and prospective studies had a pooled estimate of odds ratio 0.55 (95% confidence interval 0.35e0.89), odds ratio 0.38 (95% confidence interval 0.27e0.54; P < .0001), and odds ratio 0.49 (95% confidence interval 0.30e0.81; P ¼ .005) respectively. Conclusion: The use of indocyanine green fluorescence angiography is associated with a decrease in anastomotic leakage. This association is present in patients with severe anastomotic leakage requiring intervention as well as low colorectal anastomoses.

No abstract