Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease ...(GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity.
Mechanisms driving acute graft-versus-host disease (aGVHD) onset in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still poorly understood. To provide a ...detailed characterization of tissue-infiltrating T lymphocytes (TL) and search for eventual site-specific specificities, we developed a xenogeneic model of aGVHD in immunodeficient mice. Phenotypic characterization of xenoreactive T lymphocytes (TL) in diseased mice disclosed a massive infiltration of GVHD target organs by an original CD4
CD8
TL subset. Immunophenotypic and transcriptional profiling shows that CD4
CD8
TL comprise a major PD1
CD62L
transitional memory subset (>60%) characterized by low level expression of cytotoxicity-related transcripts. CD4
CD8
TL produce high IL-10 and IL-13 levels, and low IL-2 and IFN-γ, suggestive of regulatory function. In vivo tracking of genetically labeled CD4
or CD8
TL subsequently found that CD4
CD8
TL mainly originate from chronically activated cytotoxic TL (CTL). On the other hand, phenotypic profiling of CD3
TL from blood, duodenum or rectal mucosa in a cohort of allo-HSCT patients failed to disclose abnormal expansion of CD4
CD8
TL independent of aGVHD development. Collectively, our results show that acquisition of surface CD4 by xenoreactive CD8
CTL is associated with functional diversion toward a regulatory phenotype, but rule out a central role of this subset in the pathogenesis of aGVHD in allo-HSCT patients.
Lung ultrasonography (LUS) is an accurate method of estimating lung congestion but there is ongoing debate on the optimal number of scanning points. The aim of the present study was to compare the ...reproducibility (i.e. interobserver agreement) and the feasibility (i.e. time consumption) of the two most practiced protocols in patients hospitalized for acute heart failure (AHF). This prospective trial compared 8- and 28-point LUS protocols. Both were performed by an expert–novice pair of sonographers at admission and after 4 to 6 days on patients admitted for AHF. A structured bio-clinical evaluation was simultaneously carried out by the treating physician. The primary outcome was expert-novice interobserver agreement estimated by kappa statistics. Secondary outcomes included time spent on image acquisition and interpretation. During the study period, 43 patients underwent a total of 319 LUS exams. Expert–novice interobserver agreement was moderate at admission and substantial at follow-up for 8-point protocol (weighted kappa of 0.54 and 0.62, respectively) with no significant difference for 28-point protocol (weighted kappa of 0.51 and 0.41;
P
value for comparison 0.74 at admission and 0.13 at follow-up). The 8-point protocol required significantly less time for image acquisition at admission (mean time difference − 3.6 min for experts, − 5.1 min for novices) and interpretation (− 6.0 min for experts and − 6.3 min for novices;
P
value < 0.001 for all time comparisons). Similar differences were observed at follow-up. In conclusion, an 8-point LUS protocol was shown to be timesaving with similar reproducibility when compared with a 28-point protocol. It should be preferred for evaluating lung congestion in AHF inpatients.
# Introduction This case report illustrates the diagnostic challenges and complexities in the treatment of disseminated fusariosis. # Case An 18-year-old patient received a second allogeneic ...hematopoietic stem cell transplant (HSCT) 5 months after the first HSCT. Two days post-transplant, the patient presented neutropenic fever with diffuse multiple cutaneous papular lesions under isavuconazole prophylaxis. A diagnosis of disseminated fusariosis due to *Fusarium fujikoroi* was established. Antifungal therapy had to be adapted multiple times for efficacy and safety issues. Long-term combination therapy with posaconazole and terbinafine efficiently controlled the infection and was well tolerated. # Discussion This case report illustrates three major teaching points: (i) high clinical suspicion based on typical clinical and microbiologic findings is a key factor for the diagnosis of fusariosis; (ii) treatment is challenging due to variable antifungal agent minimal inhibitory concentrations (MICs); and (iii) long-term administration of voriconazole can be associated with multiple, less frequently seen adverse events. # Conclusion Typical skin lesions and positive blood cultures for molds should promptly rise suspicion of fusariosis. Amphotericin-B and voriconazole are the first-line agents for the treatment of fusariosis. Second-line agents such as posaconazole and terbinafine can be used.
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