RESUMEN
BACKGROUND: Percutaneous coronary intervention (PCI) outcomes for patients with significant calcification have been consistently inferior compared to patients without significant calcification. Procedural success and long-term outcomes after PCI have been worse in patients with severe coronary calcium. OBJECTIVE: A Bayesian meta-analysis of outcomes comparing rotational atherectomy (RA) with orbital atherectomy (OA) was performed. METHODS: PubMed, Embase, and Cochrane Library databases were searched through 30th November 2018 and identified 4 observational studies. RESULTS: The primary end-point, Major Adverse Cardiac Event (MACE) composing of death, MI and stroke at 1â¯year was more likely with RA (ORâ¯=â¯1.61; 95% CI: 1.11-2.33; pâ¯=â¯0.01) as compared to OA. The driver of the difference in MACE between the two groups was a statistically significant difference in mortality favoring OA (ORâ¯=â¯4.65; 95% CI: 1.36-15.87; pâ¯=â¯0.01). Peri-procedural MI, the other component of the primary end-point was 1.3 times more likely in the RA arm (ORâ¯=â¯1.35; 95% CI 0.95-1.92; p-0.09) and was not statistically different between the groups. The odds of a vascular complication were not different in the two groups (ORâ¯=â¯1.26; 95% CI: 0.73-2.17; pâ¯=â¯0.41). In an adjusted Bayesian analysis, mortality (ORâ¯=â¯3.69; 95% CI: 0.30-38.51), MACE (ORâ¯=â¯1.68; 95% CI: 0.55-5.49), MI (ORâ¯=â¯1.42; 95% CI: 0.50-4.29) and dissections/perforations (ORâ¯=â¯0.38; 95% CI: 0.10-1.38) were not different in RA and OA groups. CONCLUSION: Our study is the first published Bayesian meta-analysis comparing MACE and peri-procedural outcomes in RA compared to OA. These findings lay the foundation for a randomized comparison between the two competing technologies.
Asunto(s)
Aterectomía Coronaria , Enfermedad de la Arteria Coronaria/terapia , Intervención Coronaria Percutánea , Calcificación Vascular/terapia , Aterectomía Coronaria/efectos adversos , Aterectomía Coronaria/mortalidad , Teorema de Bayes , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/mortalidad , Calcificación Vascular/fisiopatologíaRESUMEN
OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR) has prognostic value in acute coronary syndromes. We investigated its utility for predicting heart failure (HF) admissions and major adverse cardiac outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Data on clinical, laboratory, procedural, HF admissions, and major adverse cardiac events (MACEs) (all-cause mortality, recurrence of myocardial infarction requiring intervention, stroke) for 298 consecutive patients who underwent TAVR between 2012 and 2016 in our tertiary center were collected. RESULTS: Analysis included 298 patients. The mean age was 83 ± 8 years, 51% were males, and 95% were Caucasians. The median Society of Thoracic Surgeons risk score was 9 (interquartile range: 6.3-11.8). Receiver-operating curve analysis identified a cutoff value of NLR of 4.0 for MACE after TAVR and sensitivity of 68% and specificity of 68% {area under the curve [AUC] = 0.65 [95% confidence interval (CI): 0.51-0.79], p = 0.03}. An NLR of 4.0 for HF hospitalizations after TAVR and sensitivity of 60% and specificity of 57% [AUC = 0.61 (95% CI: 0.53-0.69), p = 0.01]. NLR ≥4.0 before TAVR significantly predicted MACE after TAVR (68.4% vs. 31.6%, p = 0.02) and HF hospitalizations (58.3% vs. 41.7%, p = 0.03). NLR with TAVR risk score increased the predictive value for MACE after TAVR from AUC = 0.61 (95% CI: 0.50-0.72, p = 0.06) to AUC = 0.69 (95% CI: 0.57-0.80, p = 0.007). CONCLUSION: NLR predicts all-cause mortality, MACE, and HF hospitalization 1 year after TAVR. NLR with TAVR risk score improved predictability for MACE. Further studies for prognostication using NLR are warranted.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Insuficiencia Cardíaca/sangre , Linfocitos , Neutrófilos , Readmisión del Paciente/tendencias , Medición de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Humanos , Incidencia , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
A new hypervirulent (hypermucoviscous) clinical variant of Klebsiella pneumoniae (hvKP) has emerged over the last decade. Our goal is to identify new mechanisms, which increase the virulence hvKP. It has been shown that hvKP strains produce more biofilm than "classical" stains of K. pneumoniae, therefore we hypothesized that biofilm formation may contribute to the pathogenesis of systemic infection. To test this hypothesis, transposon mutants of the model pathogen hvKP1 were generated and screened for decreased production of biofilm. Three mutant constructs with disruptions in glnA [putatively encodes glutamine synthetase, hvKP1 glnA:: EZ::TN < KAN-2 > (glnA::Tn)], sucD [putatively encodes succinyl-CoA synthase α subunit, hvKP1 sucD:: EZ::TN < KAN-2 > (sucD::Tn)], and tag [putatively encodes transcriptional antiterminator of glycerol uptake operon, hvKP1 tag:: EZ::TN < KAN-2 > (tag::Tn)] were chosen for further characterization and use in biologic studies. Quantitative assays performed in rich laboratory medium and human ascites confirmed the phenotype and a hypermucoviscosity assay established that capsule production was not affected. However, compared with its wild-type parent, neither planktonic cells nor biofilms of glnA::Tn, sucD::Tn and tag::Tn displayed a change to the bactericidal activity of 90% human serum. Likewise, when assessed in a rat subcutaneous abscess model, the growth and survival of glnA::Tn, sucD::Tn and tag::Tn in abscess fluid was similar to hvKP1. In this report we identify three new genes that contribute to biofilm formation in hvKP1. However, decreased biofilm production due to disruption of these genes does not affect the sensitivity of these mutant constructs to 90% human serum when in planktonic form or within a biofilm. Further, their virulence in an in vivo abscess model was unaffected.
Asunto(s)
Absceso/microbiología , Biopelículas/crecimiento & desarrollo , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/fisiología , Klebsiella pneumoniae/patogenicidad , Viabilidad Microbiana , Polisacáridos Bacterianos/metabolismo , Factores de Virulencia/metabolismo , Animales , Actividad Bactericida de la Sangre , Elementos Transponibles de ADN , Modelos Animales de Enfermedad , Técnicas de Inactivación de Genes , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/inmunología , Masculino , Mutagénesis Insercional , Ratas , Ratas Long-Evans , Suero/inmunología , Factores de Virulencia/genética , Adulto JovenRESUMEN
BACKGROUND: A new hypervirulent (hypermucoviscous) clinical variant of Klebsiella pneumoniae (hvKP) has emerged over the last decade. Our goal is to identify new mechanisms, which increase the virulence hvKP compared to "classic" K. pneumoniae (cKP). METHODOLOGY/PRINCIPAL FINDINGS: Various growth assays were performed in human ascites, human serum, and laboratory medium with the hvKP strain hvKP1 (wt), randomly chosen blood isolates of cKP strains (cKP1-4), and mutant constructs deficient in the secretion of selected compounds. An in vivo mouse model that mimics infection due to hvKP and a quantitative siderophore assay were also used. It was established that a molecule(s)/factor(s) was secreted by hvKP1 significantly enhanced its growth and/or survival in human ascites. This molecule(s)/factor(s) also increased the growth and/or survival of hvKP1 in serum ex vivo and in an in vivo mouse model that measures metastatic spread after subcutaneous challenge, thereby further establishing biologic significance. Although features such as a size of <3kD, heat stability, and growth characteristics in ascites suggested this molecule(s) was a quorum-sensing compound, data presented demonstrates that this molecule(s)/factor(s) is involved in iron uptake and is likely a siderophore(s) or another iron-acquisition molecule. Although it is known that iron acquisition is critical for virulence, a novel aspect of this observation is that hvKP1 produces quantitatively more siderophores that appear to be biologically more active (increased affinity for iron or more resistant to host factors) than those produced by cKP strains. CONCLUSIONS/SIGNIFICANCE: The data presented delineates a new mechanism by which hvKP increases its pathogenic potential compared to cKP strains. This paradigm may be broadly applicable to other extraintestinal gram-negative bacilli.