The ECHO model proved to be a useful tool to increase clinicians' self-effectiveness for care of patients with Hepatitis C in Argentina.

The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community-based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct-acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0-18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4-96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7-98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI -0.24-0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.

Identification and clinical relevance of naturally occurring human CD8+HLA-DR+ regulatory T cells.

The lack of responsiveness to self and non-self Ags is normally maintained by multiple mechanisms, including the suppressive activities of several T cell subsets. In this study, we show that CD8(+) T cells from both adult peripheral blood and umbilical cord blood mononuclear cells constitutively expressing HLA-DR represent a natural human CD8(+) regulatory T cell subset. Their suppressive effect appears to be cell-to-cell contact dependent and may involve CTLA-4 signaling between neighboring T cells. These regulatory T cells can be expanded in vitro and exhibit a suppressive capacity similar to that observed in ex vivo CD8(+)HLA-DR(+) T cells. The high frequency of CD8(+)HLA-DR(+) T cells that we detected in patients with non-small cell lung cancer deserves further work to confirm their putative suppressor effect within the tumor.

A physiological role for inducible FOXP3(+) Treg cells. Lessons from women with reproductive failure.

We have previously shown a decreased frequency and function of Tregs in women suffering from recurrent spontaneous abortions (RSA). In the current study, we first investigated the expression of FOXP3 after T-cell activation. We observed that expression of FOXP3 in activated PBMCs was already present above baseline before any cell division, indicating that it was induced in cells that were previously negative for this transcription factor. Because RSA women showed a more limited expansion of FOXP3-positive cells, we next assessed the role of IL-2 signaling through STAT5, which is known to be required for generation of inducible Tregs (iTregs). We demonstrated not only that TGF-beta and IL-2 were diminished but also that the IL-2-STAT-5 signaling axis was down regulated in RSA women. Finally, in addition to a limited FOXP3(+) cells expansion in vitro, iTregs from RSA women showed a strikingly lower suppressor activity.