Trends in hospitalization and factors associated with in-hospital death among pediatric admissions with implantable cardioverter defibrillators.

BACKGROUND: As pediatric implantable cardioverter-defibrillator (ICD) utilization increases, hospital admission rates will increase. Data regarding hospitalizations among pediatric patients with ICDs are lacking. In addition, hospital mortality rates are unknown. This study aimed to evaluate (1) trends in hospitalization rates from 2000 to 2016, (2) hospital mortality, and (3) factors associated with hospital mortality among pediatric admissions with ICDs. METHODS: The Kids' Inpatient Database (2000, 2003, 2006, 2009, 2012, 2016) was used to identify all hospitalizations with an existing ICD ≤20 years of age. ICD9/10 codes were used to stratify admissions by underlying diagnostic category as: (1) congenital heart disease (CHD), (2) primary arrhythmia, (3) primary cardiomyopathy, or (4) other. Trends were analyzed using linear regression. Hospital and patient characteristics among hospital deaths were compared to those surviving to discharge using mixed multivariable logistic regression, accounting for hospital clustering. RESULTS: Of 42 570 716 hospitalizations, 4165 were admitted ≤20 years with an ICD. ICD hospitalizations increased four-fold (p = .002) between 2000 and 2016. Hospital death occurred in 54 (1.3%). In multivariable analysis, cardiomyopathy (odds ratio [OR]: 3.5, 95% confidence interval [CI]: 1.1-11.2, p = .04) and CHD (OR: 4.8, 95% CI: 1.5-15.6, p = .01) were significantly associated with mortality. In further exploratory multivariable analysis incorporating a coexisting diagnosis of heart failure, only the presence of heart failure remained associated with mortality (OR: 8.6, 95% CI: 3.7-20.0, p < .0001). CONCLUSIONS: Pediatric ICD hospitalizations are increasing over time and hospital mortality is low (1.3%). Hospital mortality is associated with cardiomyopathy or CHD; however, the underlying driver for in-hospital death may be heart failure.

Ultrafast Spectroscopic Dynamics of Quinacrine-Riboflavin Binding Protein Interactions.

Redox active cofactors play a dynamic role inside protein binding active sites because the amino acids responsible for binding participate in electron transfer (ET) reactions. Here, we use femtosecond transient absorption (FsTA) spectroscopy to examine the ultrafast ET between quinacrine (Qc), an antimalarial drug with potential anticancer activity, and riboflavin binding protein (RfBP) with a known Kd = 264 nM. Steady-state absorption reveals a ∼ 10 nm red-shift in the ground state when QcH32+ is titrated with RfBP, and a Stern-Volmer analysis shows ∼84% quenching and a blue-shift of the QcH32+ photoluminescence to form a 1:1 binding ratio of the QcH32+-RfBP complex. Upon selective photoexcitation of QcH32+ in the QcH32+-RfBP complex, we observe charge separation in 7 ps to form 1[QcH3_red•+-RfBP•+], which persists for 138 ps. The FsTA spectra show the spectroscopic identification of QcH3_red•+, determined from spectroelectrochemical measurements in DMSO. We correlate our results to literature and report lifetimes that are 10-20× slower than the natural riboflavin, Rf-RfBP, complex and are oxygen independent. Driving force (ΔG) calculations, corrected for estimated dielectric constants for protein hydrophobic pockets, and Marcus theory depict a favorable one-electron ET process between QcH32+ and nearby redox active tyrosine (Tyr) or tryptophan (Trp) residues.