The great imitator with no diagnostic test: pyoderma gangrenosum

Pyoderma gangrenosum is a rare, neutrophil‐mediated, auto‐inflammatory dermatosis that wound care specialists must be prepared to recognise. This condition has clinical features analogous to infectious processes. There is no specific diagnostic test and the diagnosis is usually obtained from exclusion. Its early recognition and proper management with prompt initiation of immunosuppressive therapy are essential to improve the quality of life and the prognosis of patients.     

Donor-recipient age interaction and the impact on clinical results after heart transplantation

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.     

ZnO Nanoparticles-Modified Dressings to Inhibit Wound Pathogens

Zinc oxide (ZnO) nanoparticles (NPs) have been investigated for various skin therapies in recent years. These NPs can improve the healing and modulate inflammation in the wounds, but the mechanisms involved in such changes are yet to be known. In this study, we have designed a facile ZnO nano-coated dressing with improved antimicrobial efficiency against typical wound pathogens involved in biofilm and chronic infections. ZnO NPs were obtained by hydrothermal method and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. Antibacterial and antibiofilm effects were evaluated against laboratory and clinical isolates of significant Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Enterococcus faecalis) opportunistic pathogens, by quantitative methods. Our results have shown that the developed dressings have a high antibacterial efficiency after 6–24 h of contact when containing 0.6 and 0.9% ZnO NPs and this effect is similar against reference and clinical isolates. Moreover, biofilm development is significantly impaired for up to three days of contact, depending on the NPs load and microbial species. These results show that ZnO-coated dressings prevent biofilm development of main wound pathogens and represent efficient candidates for developing bioactive dressings to fight chronic wounds.     

Pro-inflammatory cytokines favor the emergence of ETV6-RUNX1-positive pre-leukemic cells in a model of mesenchymal niche

ETV6-RUNX1 (E/R) fusion gene, arising in utero from translocation t(12;21)(p13:q22), is the most frequent alteration in childhood acute lymphoblastic leukemia (ALL). However, E/R is insufficient to cause overt leukemia since it generates a clinically silent pre-leukemic clone which persists in the bone marrow but fails to out-compete normal progenitors. Conversely, pre-leukemic cells show increased susceptibility to transformation following additional genetic insults. Infections/inflammation are the most accredited triggers for mutations accumulation and leukemic transformation in E/R⁺ pre-leukemic cells. However, precisely how E/R and inflammation interact in promoting leukemia is still poorly understood. Here we demonstrate that IL6/TNFα/ILβ pro-inflammatory cytokines cooperate with BM-MSC in promoting the emergence of E/R⁺ Ba/F3 over their normal counterparts by differentially affecting their proliferation and survival. Moreover, IL6/TNFα/ILβ-stimulated BM-MSC strongly attract E/R⁺ Ba/F3 in a CXCR2-dependent manner. Interestingly, E/R-expressing human CD34⁺IL7R⁺ progenitors, a putative population for leukemia initiation during development, were preserved in the presence of BM-MSC and IL6/TNFα/ILβ compared to their normal counterparts. Finally, the extent of DNA damage increases within the inflamed niche in both control and E/R-expressing Ba/F3, potentially leading to transformation in the apoptosis-resistant pre-leukemic clone. Overall, our data provide new mechanistic insights into childhood ALL pathogenesis.