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1.
J Neuroimmunol ; 370: 577931, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35872506

RESUMO

Background The neutrophil-to-lymphocyte ratio (NLR) may predict poor outcomes in adult anti-NMDAR encephalitis (NMDARE). The association of NLR with outcomes in pediatric NMDARE was examined. Methods Pediatric NMDARE patients (N = 36) were retrospectively studied. Results High NLR (>6) had a higher proportion of tumors (43% versus 7%) and higher intubation rates (100% versus 38%, p = 0.008). Multivariate analyses showed that high NLR did not correlate with one-year outcomes, inpatient length of stay (LOS), or with tumor, but was associated with intubation and rehabilitation LOS. Conclusion NLR is associated with intubation and rehabilitation LOS. Further investigation is needed for prognostic biomarkers in NMDARE.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Criança , Humanos , Intubação Intratraqueal , Linfócitos , Neutrófilos , Receptores de N-Metil-D-Aspartato , Estudos Retrospectivos
2.
Antimicrob Agents Chemother ; 66(1): e0165221, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34780273

RESUMO

Echinocandins are frontline antifungal agents in the management of invasive infections due to multidrug resistant Candida auris. The study aimed to evaluate echinocandin resistance in C. auris isolates of multicentric origin, identify the resistance mechanism, and analyze the pharmacodynamic response to caspofungin in a neutropenic mouse model of infection. A total of 199 C. auris isolates originating from 30 centers across India were tested for susceptibility to echinocandins. Isolates with reduced susceptibility were evaluated for FKS1 mutations and in vivo response to caspofungin in a murine model of disseminated candidiasis. In addition, the response to echinocandins was assessed in light of in vitro growth kinetics, chitin content; and transcript levels of chitin synthase and FKS1 genes. We report 10 resistant C. auris isolates with four FKS1 mutations: F635Y (n = 2), F635L (n = 4), S639F (n = 3), and R1354S (n = 1). Of these, F635Y and R1354S exhibited the most profound resistance in mouse model of disseminated infection. S639F and F635L mutations conferred a moderate in vivo resistance, whereas wild-type isolates exhibiting borderline MIC were susceptible in vivo. FKS1 genotype was more accurate predictor of in vivo response than the MIC of the isolates. Isolates with high basal or inducible chitin content exhibited higher in vitro MIC in FKS1 mutant compared to wild type. FKS1 mutations play a major role in clinically relevant echinocandin resistance in C. auris with differential in vivo outcomes. This study could have implications for clinical practice and, therefore, warrants further studies.


Assuntos
Antifúngicos , Candida auris , Candidíase/tratamento farmacológico , Farmacorresistência Fúngica , Equinocandinas , Proteínas Fúngicas , Animais , Antifúngicos/farmacologia , Candida auris/efeitos dos fármacos , Modelos Animais de Doenças , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Proteínas Fúngicas/genética , Genótipo , Camundongos , Testes de Sensibilidade Microbiana , Mutação/genética
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