- Blockade of PD-1 Attenuated Post-Sepsis Aspergillosis via The Activation Of IFN-γ and The Dampening of IL-10.
Blockade of PD-1 Attenuated Post-Sepsis Aspergillosis via The Activation Of IFN-γ and The Dampening of IL-10.
Shock. 2019 Jul 11;:
Authors: Vu CTB, Thammahong A, Yagita H, Azuma M, Hirankarn N, Ritprajak P, Leelahavanichkul A
BACKGROUND: Nosocomial aspergillosis in patients with sepsis have emerged in the past few years. Blockade of PD-1/PD-L pathway has tended to become a promising therapeutic strategy as it improved the outcome of bacterial sepsis and post-sepsis secondary fungal infection. Recently, the controversial effects of PD-1 blockade on infectious diseases, including aspergillosis, have been demonstrated, therefore, the efficacy of anti-PD-1 drug still remains to be elucidated.
METHODS: Cecal ligation and puncture (CLP) was conducted as a mouse sepsis model. Aspergillus fumigatus spores were intravenously inoculated on day 5 post-CLP, when the immune cells succumbed to exhaustion. Amphotericin B was medicated together with or without anti-PD-1 treatment after Aspergillus infection.
RESULTS: Amphotericin B alone was not effective to treat the CLP-mice with secondary aspergillosis. In contrast, anti-fungal medication with the adjunctive anti-PD-1 treatment attenuated the fungal burdens in blood and internal organs, and improved the survival rate of the mice with secondary aspergillosis. These outcomes of PD-1 blockade were concurring with the enhanced CD86 expression on splenocytes, the augmented serum IFN-γ and the dampened IL-10. Activated T cells from anti-PD-1 treated mice also highly increased IFN-γ and diminished IL-10 production.
CONCLUSION: The blockade of PD-1 on post-sepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.
PMID: 31306346 [PubMed - as supplied by publisher]
- Antibiotic-related adverse events in paediatrics: unique characteristics.
Antibiotic-related adverse events in paediatrics: unique characteristics.
Expert Opin Drug Saf. 2019 Jul 15;:1-8
Authors: Principi N, Esposito S
Introduction: Antibiotics have saved and are still saving countless human lives from the burden of infectious diseases. However, as with all other drugs, they can cause adverse events. Generally, these are uncommon, mild and spontaneously resolving. However, in some cases, they can cause relevant clinical problems. Compared with adults, children, particularly in the first years of life, have a higher risk of antibiotic-related adverse events for several reasons. Areas covered: In this paper, the conditions that can contribute to the elevated risk of antibiotic-related adverse events in children are discussed. Expert opinion: Antibiotic stewardship can be a solution to limit antibiotic abuse and misuse and consequently the incidence of antibiotic-related adverse events in children. Moreover, most of the antibiotic-associated adverse events can be avoided with more extensive pre-marketing medicine investigations, improved postmarket safety surveillance system, increased transparency throughout the clinical research enterprise, increased training of clinical pharmacologists and paediatric researchers, expanded pool of paediatric patients, and providing additional funding and incentives for paediatric drug development.
PMID: 31305171 [PubMed - as supplied by publisher]
- Infective endocarditis without biological inflammatory syndrome: Description of a particular entity.
Infective endocarditis without biological inflammatory syndrome: Description of a particular entity.
Arch Cardiovasc Dis. 2019 Jul 11;:
Authors: Ribeyrolles S, Ternacle J, San S, Lepeule R, Moussafeur A, Faivre L, Nahory L, Huguet R, Gallien S, Decousser JW, Fihman V, Fiore A, Mongardon N, Lim P, Oliver L
BACKGROUND: Bacterial infective endocarditis (IE) is rarely suspected in patients with a low C-reactive protein (CRP) concentration.
AIMS: To address the incidence, characteristics and outcome of left-sided valvular IE with low CRP concentration.
METHODS: This was a retrospective analysis of cases of IE discharged from our institution between January 2009 and May 2017. The 10% lowest CRP concentration (<20mg/L) was used to define low CRP concentration. Right-sided cardiac device-related IE, non-bacterial IE, sequelar IE and IE previously treated by antibiotics were excluded.
RESULTS: Of the 469 patients, 13 (2.8%; median age 68 [61-76] years) had definite (n=8) or possible (n=5) left-sided valvular IE with CRP<20mg/L (median 9.3 [4.7-14.2] mg/L). The median white blood cell count was 6.3 (5.3-7.5) G/L. The main presentations were heart failure (n=7; 54%) and stroke (n=3; 23%). Transthoracic echocardiography (TTE) showed vegetations (n=5) or isolated valvular regurgitation (n=4). Overall, eight patients (62%) had severe valvular lesions on transoesophageal echocardiography (TOE), and nine patients (69%) underwent cardiac surgery. All patients survived at 1-year follow-up. Bacterial pathogens were documented in eight patients (streptococci, coagulase-negative Staphylococcus, Corynebacteriumjeikeium, HACEK group, Coxiella burnetii, Bartonella henselae) using blood cultures, serology or valve culture and/or polymerase chain reaction analysis.
CONCLUSIONS: Left-sided valvular IE with limited or no biological syndrome is rare, but is often associated with severe valvular and paravalvular lesions. TOE should be performed in presence of unexplained heart failure, new valvular regurgitation or cardioembolic stroke when TTE is insufficient to rule out endocarditis, even in patients with a low CRP concentration.
PMID: 31303461 [PubMed - as supplied by publisher]
- Stewardship für Antibiotika in der Pädiatrie.
Stewardship für Antibiotika in der Pädiatrie.
Drug Res (Stuttg). 2018 Nov;68(S 01):S6-S7
Authors: Müller A
PMID: 30453362 [PubMed - indexed for MEDLINE]