Search

We recently investigated the prognostic impact of a Chronic Care Model (CCM)-based healthcare program applied in primary care in Tuscany Region mainly run by multidisciplinary teams composed of general practitioners (GPs) and nurses. The project included proactively planned follow-up visits for each patient, individualized counselling to optimize lifestyle modifications and adherence to appropriate diagnostic and therapeutic pathways. 1761 patients with Chronic heart failure (CHF) directly enrolled by the GPs were matched with 3522 CHF controls not involved in the project. Over a 4-year follow-up in the CCM group a higher CHF hospitalization rate was found (12.1 vs 10.3 events/100 patient-years; incidence rate ratio [IRR] 1.15, p=0.0030), whereas mortality was lower (10.8 vs 12.6 events/100 patient-years; IRR 0.82, p0.0001). The CCM status was independently associated with a 34% increase in the risk of CHF hospitalization and a 18% reduction in the risk of death (p0.0001 for both). The CCM status was associated with a 50% increase in the rate of planned Heart failure (HF) hospitalizations whereas the rate of 1-month CHF readmissions showed no differences. Such a divergent trend could be explained by the direct involvement of GPs in the CCM program, leading them to a better awareness of patients' clinical status, and then to a more frequent use of clinical pathways and facilities, including hospitalization. It is reasonable to argue that not all hospitalizations must necessarily be considered as a poor outcome, as they often provide additional opportunities to improve therapies, optimize patient education, or define follow-up strategies. The evidence of a divergent trend between mortality and hospitalization in our population might support the clinical importance of a multidisciplinary approach for the management of patients with HF.

How dermal papilla (DP) niche cells regulate hair follicle progenitors to control hair growth remains unclear. Using Tbx18Cre to target embryonic DP precursors, we ablate the transcription factor Sox2 early and efficiently, resulting in diminished hair shaft outgrowth. We find that DP niche expression of Sox2 controls the migration speed of differentiating hair shaft progenitors. Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased BMP inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we identify upregulated BMP signaling in knockout hair shaft progenitors and demonstrate that Bmp6 inhibits cell migration, an effect that can be attenuated by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and shows reduced migration and increased BMP activity of hair shaft progenitors. Collectively, our data identify Sox2 as a key regulator of hair growth that controls progenitor migration by fine-tuning BMP-mediated mesenchymal-epithelial crosstalk. Mesenchymal-epithelial crosstalk is a prominent feature of hair follicle development and regeneration. Clavel et al. find that Sox2 regulates the ability of the dermal papilla niche to control hair shaft progenitor migration and thus hair outgrowth. Sox2 fine-tunes BMP signal output, which in turn attenuates progenitor migration rates.