Existing literature on febrile neutropenia (FN) has categorized patients with acute leukemia or those undergoing allogeneic stem cell transplantation (SCT) as being high risk for severe infection, ...bacteremia, and poor outcomes. Comprehensive studies of infection risk in pediatric high-risk neuroblastoma (NB-HR) during induction chemotherapy are limited, and mostly merged within the solid tumor (ST) group. Therefore, it is unclear whether infectious complications and outcomes for NB-HR are the same as in other ST groups. We conducted a retrospective medical record review of pediatric FN patients in a single center from March 2009 to December 2016. FN episodes were categorized into five groups based on underlying diagnosis (acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), NB-HR during induction chemotherapy, other solid tumors, and SCT). Comparative analyses of infectious complications between patients with NB-HR and those with other types of cancer diagnoses were performed. A total of 667 FN episodes (FNEs) were identified in 230 patients. FNEs occurred in 82 episodes with NB-HR. Bloodstream infection (BSI) occurred in 145 (21.7%) of total FN episodes. The most isolated organisms were the viridians group streptococci (VGS) (25%). NB-HR patients have higher rates of VGS bacteremia (OR 0.15, 95% CI 0.04, 0.56) and are more likely to be admitted to the Pediatric Intensive Care Unit (PICU) compared to patients with other solid tumors (OR 0.36, 95% CI 0.15, 0.84). Interestingly, there is no difference in VGS rates between patients with NB-HR and those with AML despite the fact that NB-HR patients do not receive a cytosine arabinoside (AraC)-based regimen. This large neuroblastoma cohort showed that patients with NB-HR during induction chemotherapy are at higher risk for VGS bacteremia and PICU admissions compared with patients with other solid tumors. Further prospective studies are needed to investigate infection-related complications in this high-risk group and to improve morbidity and mortality.
The structure of the CH(2)ClF···HCCH dimer has been determined using both chirped-pulse and resonant cavity Fourier-transform microwave spectroscopy. The complex has C(s) symmetry and contains both a ...double C-H···π interaction, in which one π-bond acts as acceptor to two hydrogen atoms from the CH(2)ClF donor, and a weak C-H···Cl interaction, with acetylene as the donor. Analysis of the rotational spectra of four isotopologues (CH(2)(35)ClF···H(12)C(12)CH, CH(2)(37)ClF···H(12)C(12)CH, CH(2)(35)ClF···H(13)C(13)CH, and CH(2)(37)ClF-H(13)C(13)CH) has led to a structure with C-H···π distances of 3.236(6) Å and a C-H···Cl distance of 3.207(22) Å, in good agreement with ab initio calculations at the MP2/6-311++G(2d,2p) level. Both weak contacts are longer than those observed in similar complexes containing a single C-H···π interaction that lies in the C(s) plane; however, this appears to be the first double C-H···π contact to be studied by microwave spectroscopy, so there is little data for direct comparison. The rotational and chlorine nuclear quadrupole coupling constants for the most abundant isotopologue are: A = 5262.899(14) MHz, B = 1546.8074(10) MHz, C = 1205.4349(7) MHz, χ(aa) = 28.497(5) MHz, χ(bb) = -65.618(13) MHz, and χ(cc) = 37.121(8) MHz.
The structure of methyldifluoroisocyanato silane, MeF2SiNCO (2), has been studied by molecular rotational spectroscopy. The rotational spectrum has a complicated structure from 14N nuclear quadrupole ...coupling and internal rotation of the methyl group. Cavity Fourier-transform microwave spectroscopy measurements were important for providing high spectral resolution to analyze the quadrupole and internal rotation fine structure. Broadband chirped-pulse Fourier-transform microwave spectroscopy was used to achieve high measurement sensitivity making it possible to observe the lower abundance C, N, O, and Si isotopologues in natural abundance for structure determination. Analysis of the microwave spectrum of the most abundant isotopomer of MeF2SiNCO (2) yields the rotational constants: A = 3827.347(7), B = 1264.5067(14), and C = 1240.6182(11) MHz. The spectrum has been analyzed in the I r representation for Cs symmetry, with inclusion of the 3-fold rotor (V 3 = 446(50) cm–1). A partial substitution structure was obtained for the C, Si, N, and O atoms. The analysis was assisted by calculations of the equilibrium structure, using a 6-311++G (3df, 3pd) basis set, with calculations at each of the B3LYP, MP2, and CCSD(T) levels. The calculated and experimental rotational constants are only consistent with a trans-orientation at each of the HCSiN, CSiNC, and SiNCO centers; there is relatively close agreement between the experimental and the theoretical structures, especially at the CCSD(T) level. In addition, the observed low value for the 14N quadrupole coupling term (χ bb – χ cc ) implies a wide SiNC angle, which is consistent with the calculated values: 165.3° (B3LYP), 157.6° (MP2), and 157.4° (CCSD(T)). The skeletal bending potential is discussed.
Background. Sickle cell disease (SCD) is a hemoglobinopathy with increasing global prevalence resulting in pain episodes and multiorgan complications. Complications of SCD have been shown to ...adversely impact health-related quality of life (HRQOL) comprised of physical, social, and emotional domains; hence, HRQOL measures can serve as an effective evaluator of disease burden. Hydroxyurea (HU) and other disease-modifying therapies have demonstrated to significantly improve clinical outcomes in patients with SCD. Medication adherence is an essential mediator of the clinical benefits of these therapies; low adherence has been shown to increase disease burden and healthcare utilization. This systematic literature review intends to determine the association between adherence to disease-modifying therapies and HRQOL in patients with SCD. Methods. We found a total of 12 articles involving 788 participants, which included both patients with SCD and caregivers/parents. Adherence was measured using self-report instruments, laboratory markers, such as fetal hemoglobin and mean corpuscular volume, and mHealth medication trackers. HRQOL was measured using self-report instruments. Results. All studies demonstrated a correlation between higher HU adherence and better HRQOL scores. Higher HU adherence was associated with lower pain impact, less frequent pain episodes, less fatigue, and improved physical function and mobility, reflecting better physical HRQOL outcomes. Higher adherence was also associated with improved emotional response, decreased anxiety and depressive symptoms, and better social functioning and peer relationships. In addition, our findings indicated that having less frequent barriers to HU adherence was associated with better HRQOL scores. No studies evaluated HRQOL outcomes in relation to adherence to l-glutamine, voxelotor, or crizanlizumab. Conclusions. Optimizing HU adherence has the potential to improve HRQOL in patients with SCD in addition to reducing healthcare utilization and improving treatment satisfaction. Addressing barriers to HU adherence can positively strengthen the relationship between adherence and HRQOL to potentially improve patient outcomes.
C–H···π Interactions in the CHBrF2···HCCH Weakly Bound Dimer Obenchain, Daniel A; Bills, Brandon J; Christenholz, Cori L ...
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
11/2011, Letnik:
115, Številka:
44
Journal Article
Recenzirano
The microwave spectra of four isotopologues of the CHBrF2···HCCH weakly bound dimer have been measured in the 6–18 GHz region using chirped-pulse and Balle–Flygare Fourier-transform microwave ...spectroscopy. Spectra of 13CH79BrF2 and 13CH81BrF2 monomers have also been measured, and spectroscopic constants are reported. Measurement of spectra for the 79Br and 81Br isotopologues of CHBrF2 complexed with both 12C2H2 and 13C2H2 have allowed the determination of a structure with C s symmetry for this complex. CHBrF2 interacts with the triple bond of acetylene via a C–H···π contact (R(H···π) = 2.670(8) Å) with the Br atom lying in the ab plane, located 3.293(40) Å from a hydrogen atom of the HCCH molecule. The structure of CHBrF2···HCCH has been compared with recently studied related acetylene complexes, including a comparison with (and further structural analysis of) the CHClF2···HCCH complex.
Invasive fungal diseases (IFDs) are opportunistic infections that result in significant morbidity and mortality in pediatric oncology patients. Predictive risk tools for IFD in pediatric cancer are ...not available.
We conducted a 7-year retrospective study of pediatric oncology patients with a diagnosis of febrile neutropenia at UCM Comer Children's Hospitals. Fourteen clinical, laboratory, and treatment-related risk factors for IFD were analyzed. Stepwise variable selection for multiple logistic regression was used to develop a risk prediction model for IFD. Two comparative analyses have been conducted: (i) all suspected IFD cases and (ii) all proven and probable IFD cases.
A total of 667 febrile neutropenia episodes were identified in 265 patients. IFD was diagnosed in 62 episodes: 13 proven, 27 probable, and 22 possible. In the final multiple logistic regression models, 5 variables were independently significant for both analyses: fever days, neutropenia days, hypotension, and absolute lymphocyte count <250 at the time of diagnosis. The odds ratio and a relative weight for each factor were then calculated and summed to calculate a predictive score. A risk score of ≤4 and ≤5 (10/11 maximum) for each model signifies low risk, respectively (<1.2% incidence). Model discrimination was evaluated by the area under the receiver operator characteristics curve with an area under the curve of 0.95/0.94 for each model.
Our prediction IFD risk models perform well, are easy-to-use, and are based on readily available clinical data. Profound lymphopenia absolute lymphocyte count <250 mm3 could serve as a new important prognostic marker for the development of IFD in pediatric cancer and hematopoietic stem cell transplant patients.
Abstract
Background
Engraftment fever (EF) during stem cell transplantation (SCT) is likely due to non infectious causes like immune reconstitution syndrome (IRS) or engraftment syndrome (ES). Few ...studies have looked at the rate of infection causing fever during engraftment. There is no good evidence to guide the approach to evaluation and empiric treatment of infections during EF.
Methods
Retrospective record review of pediatric SCT (autologous and allogenic) patients with a diagnosis of febrile neutropenia (FN) during engraftment period (days +7 to +30 post transplant). FN episodes classified as either EF or non-engraftment fever (NEF). EF = new onset fever in temporal relationship to neutrophil recovery (4 days before through 1 day after neutrophil engraftment (ANC >500/mm3). NEF = fever without signs of neutrophil recovery (ANC < 100/mm3 without significant rise ±4 days of fever onset). Only first FN during engraftment was included. Episodes meeting neither criteria were excluded.
Results
112 patients had 115 FN episodes (FNEs) identified: NEF 81 (71.5%); EF 34 (29.5%). In multivariable analysis: Neuroblastoma as underlying diagnosis (odds ratio OR=3.2, 95% CI 2.31-6.54, P< 0.01), G-CSF administration before day +7 (OR=2.8, 95% CI 1.92-4.65, P=0.03), absolute monocyte count (AMC) >100/mm3 at FN presentation (OR=2.9, 95% CI, 1.11 to 7.55, P=0.02), were associated with an increased risk of EF compared with NEF. Most EF episodes (26/34, 76%) had no specific infectious etiology identified; 8 had IFIs (24%) 3 proven, 2 probable, 3 possible). IFI rate was higher in EF than NEF group (24% vs 5%) (OR=4.5, 95% CI, 2.11 to 9.55, P< 0.01. EF episodes were more likely to be admitted to the intensive care unit (OR=2.3, 95% CI, 1.88 to 6.35) and had higher 30-day mortality (OR =4.52, 95% CI, 0.37 to 6.55) than NEF.
Table 3
table 2
Conclusion
Engraftment fever may have an infectious component. Work-up to exclude IFI and empirical antifungal therapy should be considered especially with prolonged fever and supportive clinical or radiological data. Large multi-center prospective studies are needed to further define infectious complications and determine the approach to engraftment fever. Early detection of IFI in this high-risk group may lead to improved morbidity and mortality.
Disclosures
All Authors: No reported disclosures
The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and ...epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx).
The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes.
A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors.
Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.
Survival for patients with recurrent central nervous system (CNS) neuroblastoma remains poor. A single‐institutional study demonstrated the potential of multimodality therapy, including compartmental ...intrathecal radioimmunotherapy (cRIT) with 131I‐3F8 or 131I‐8H9 to increase the survival of neuroblastoma patients with CNS relapse. However, not all patients are able to receive this therapy. We report three patients with CNS neuroblastoma who remain disease‐free 3–9 years after receiving multimodality treatment without cRIT. Additional studies to identify patients most likely to benefit from cRIT are warranted.
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