Cat Scratch Disease: 9 Years of Experience at a Pediatric Center.

Background: A more complete understanding of the epidemiology, risk factors, and clinical features of cat scratch disease (CSD) in children could help guide patient care. Methods: We conducted a retrospective analysis of children presenting to a tertiary pediatric hospital system in Atlanta, Georgia between January 1, 2010 and December 31, 2018 who had serology, polymerase chain reaction, and/or cytopathological results consistent with a Bartonella henselae infection. We also retrospectively reviewed veterinary diagnostic results performed at the University of Georgia from 2018 to 2020 to ascertain the burden of bartonellosis in companion animals within the state. Results: We identified 304 children with CSD over 9 years with the largest proportion of diagnoses made during August (41 of 304, 13.5%) and September (47 of 304, 15.5%). The median age of child cases was 8.1 years (interquartile range [IQR], 5.4-12.1); 156 (51.3%) were female; 242 of 262 (92.4%) reported feline exposure; and 55 of 250 (22%) reported canine exposure of those with exposure histories documented in the medical record. Although lymphadenopathy was present on physical examination in the majority of cases (78.8%), atypical presentations lacking lymphadenopathy were also common (63 of 304, 20.7%). Among children with radiographic imaging, 20 of 55 (36.4%) had splenomegaly and 21 of 55 (38.1%) had splenic and/or hepatic microabscesses. Among veterinary data, Bartonella seroprevalence was 12 of 146 (8.2%), all among canines, with a geographic distribution that spanned the state of Georgia. Conclusions: Distinguishing clinical features of CSD included subacute regional lymphadenopathy in school-aged children in the late summer, almost all of whom had cat exposure. Atypical clinical manifestations of CSD were also commonly identified.

Understanding Viral and Immune Interplay During Vertical Transmission of HIV: Implications for Cure.

Despite the significant progress that has been made to eliminate vertical HIV infection, more than 150,000 children were infected with HIV in 2019, emphasizing the continued need for sustainable HIV treatment strategies and ideally a cure for children. Mother-to-child-transmission (MTCT) remains the most important route of pediatric HIV acquisition and, in absence of prevention measures, transmission rates range from 15% to 45% via three distinct routes: in utero, intrapartum, and in the postnatal period through breastfeeding. The exact mechanisms and biological basis of these different routes of transmission are not yet fully understood. Some infants escape infection despite significant virus exposure, while others do not, suggesting possible maternal or fetal immune protective factors including the presence of HIV-specific antibodies. Here we summarize the unique aspects of HIV MTCT including the immunopathogenesis of the different routes of transmission, and how transmission in the antenatal or postnatal periods may affect early life immune responses and HIV persistence. A more refined understanding of the complex interaction between viral, maternal, and fetal/infant factors may enhance the pursuit of strategies to achieve an HIV cure for pediatric populations.

Urinary Tract Infections With Extended-spectrum-ß-lactamase-producing Bacteria: Case-control Study.

BACKGROUND: Urinary tract infections (UTI) are the most common bacterial infections among infants and young children with fever without a source. Extended-spectrum ß-lactamases (ESBLs) have emerged as emerging cause of UTI globally; however, data about risk factors and clinical features of children with ESBL-UTI have been scarce. OBJECTIVE: To describe the predisposing risk factors, clinical and microbiologic features associated with pediatric UTIs caused by ESBL-producing bacteria (ESBL-PB). METHODS: Our nested case-control study ran from January 1, 2012 to December 31, 2016. Pediatric patients with ESBL-PB UTI were compared with patients with non-ESBL-PB UTI matched for age and year of diagnosis. RESULTS: A total of 720 children were enrolled (240 cases and 480 controls). Patients with ESBL-PB UTI were more likely to have a history of prior intensive care unit (ICU) admission (22.5% vs. 12.3%, P < 0.001), at least one underlying comorbidity (19.2% vs. 5.8%, P < 0.001), prior hospitalization (47.1% vs. 32.9%, P < 0.001), exposure to a cephalosporin antibiotic within 30 days before culture (7.5% vs. 4.2%, P = 0.035), and to have cystostomy (7.9% vs. 1.5%, P < 0.001) compared with those with non-ESBL-PB UTI. Patients with ESBL-PB UTI were more likely to present with hypothermia (48.8% vs. 38.5%, P = 0.009); had significantly longer average hospital stays {8.7 days [95% confidence interval (CI): 3.2-14.3] vs. 4.0 days (95% CI: 2.5-5.5)} and were more likely to be admitted to the ICU [odds ratio (OR) 1.8; 95% CI: 1.1-2.9). Multivariate analysis determined that only having cystostomy (OR 3.7; 95% CI: 1.4-9.4] and at least one underlying comorbidity (OR 2.4; 95% CI: 1.3-4.3) were the independent risk factors for ESBL-PB UTI. All ESBL-PB isolates tested against meropenem were susceptible, majority were resistant to multiple non-beta-lactam antibiotics. CONCLUSIONS: Children with underlying comorbidities and cystostomy are at higher risk for ESBL-PB UTI, but majority of ESBL cases were patients without any known risk factors. Clinical signs/symptoms and commonly used biochemical markers were unreliable to differentiate cases caused by ESBL-PB from those caused by non-ESBL-PB. Further research is needed to elucidate the conditions most associated with ESBL-PB UTIs among children to properly guide empirical therapy in patients at-risk for these infections, to improve the outcomes, and finally, to determine strategies for rational antimicrobial use.

A novel voltammetry offline coupled MALDI/TOF MS characterization of electrochemical reaction products and the voltammetric determination of febuxostat in human plasma.

A simple offline coupling voltammetry-MALDI/TOF MS procedure is presented for studying electrochemical reactions. It was utilized for the characterization of the electro-reduction products of febuxostat in methanolic acetate buffer (0.1 M, pH 5). The MS analysis reveals that the carboxylic and nitrile groups are the electro-reducible groups at -0.9338 and -1.5503 V with the conversion to aldehydic and amino groups, respectively. The developed voltammetric method was validated and applied successfully for the drug determination in pharmaceutical tablets and real plasma samples within the linearity ranges 0.03-2 and 0.4-5 µg mL-1, respectively.

A novel HPLC-DAD method for simultaneous determination of febuxostat and diclofenac in biological samples: pharmacokinetic outcomes.

AIM: To develop a simple HPLC-DAD method for simultaneous determination of febuxostat (FEB) and diclofenac (DIC) in biological samples to assess pharmacokinetic outcomes of their coadministration. Methodology & results: Sample preparation was performed by liquid-liquid extraction. Drugs analysis was done on C18 column using methanol-formic acid pH 2.1 (76:24, v/v) as mobile phase and time-programmed UV detection. Lower limits of quantitation for FEB and DIC were 10 and 20 ng/ml, respectively. Baseline pharmacokinetics were similar to published data on either drug alone. Coadministration led to more than twofold increase in FEB Cmax and AUC together with a reduced hepatic uptake in rats. CONCLUSION: DIC interfered with initial distribution and terminal clearance of FEB potentially due to reduced FEB hepatic uptake.

Simultaneous determination of methocarbamol and aspirin in presence of their pharmacopeial-related substances in combined tablets using novel HPLC-DAD method.

Objective and Significance: Methocarbamol (MET) and aspirin (ASP) are widely used as a muscle relaxant combination. The USP reports guaifenesin (GUA) and salicylic acid (SAL) as related substances and hydrolytic products of MET and ASP, respectively. This work aimed at developing and validating a simple and sensitive RP-HPLC method for the determination of both drugs as well as their related substances (at their pharmacopeial limits) in their bulk powders, laboratory prepared mixtures, and MET-ASP combined tablets. Methods and Results: Chromatographic separation was achieved in less than 9 min with the required resolution, peak symmetry, and accuracy on C18 column using isocratic elution system of diluted acetic acid (pH 3.2): acetonitrile at the ratio of 79: 21, v/v, at a flow rate of 1 mL/min. Detection was achieved with photodiode array at 233 nm for MET, GUA, and SAL and at 273 nm for ASP. The developed method has been validated as per ICH guidelines and the calibration plots were linear over the concentration ranges of 2-150, 0.4-30, 25-450, and 0.2-27 µg/mL for MET, GUA, ASP, and SAL, respectively. Conclusion: The optimized method proved to be specific, robust and precise for the quality control of the studied drugs in pharmaceutical preparations to ascertain that their related substances are not exceeding the permitted pharmacopeial limits.

High-performance thin-layer chromatographic methods for the determination of febuxostat and febuxostat/diclofenac combination in human plasma.

Two simple, sensitive and specific high-performance thin-layer chromatographic (HPTLC) methods were developed for the determination of febuxostat (FEB) individually, and simultaneously with diclofenac (DIC) in human plasma. Method A presents the first HPTLC-ultraviolet attempt for FEB determination in human plasma. FEB was separated from endogenous plasma components (at hRF = 70) with ethyl acetate-methanol-water (9:2:1, v/v) mixture as mobile phase and quantified by densitometry at its λmax (315 nm). Method B is considered the first attempt for the simultaneous determination of FEB and DIC in human plasma. A mixture of petroleum ether-chloroform-ethyl acetate-formic acid (7.5:1:2.5:0.25, v/v) was used as the mobile phase. The two drugs were separated at hRF of 39 and 60 for FEB and DIC, respectively. FEB and DIC were quantified by densitometry at their isoabsorptive point (289 nm). FEB calibration plots were linear between 0.1 and 7 µg mL-1 in both methods A and B. In method B, DIC showed linear response in the range of 0.08-8 µg mL-1. Sample preparation was performed by liquid-liquid extraction using diethyl ether. Both methods did not record any interference from plasma matrix, the studied drugs' metabolites or their decomposition products. They were successfully applied for the determination of the studied drugs in healthy male volunteers after oral administration of FEB or FEB/DIC dosage forms. FEB plasma concentration increased significantly when given with DIC. The proposed methods provided very simple, rapid and cheap approaches that might be attractive for the future pharmacokinetic and bioavailability studies of FEB and/or DIC.

HPTLC and Spectrophotometric Estimation of Febuxostat and Diclofenac Potassium in Their Combined Tablets.

An accurate, precise, rapid, specific and economic high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitative determination of febuxostat (FEB) and diclofenac potassium (DIC). The chromatographic separation was performed on precoated silica gel 60 GF254 plates with chloroform-methanol 7:3 (v/v) as the mobile phase. The developed plates were scanned and quantified at 289 nm. Experimental conditions including band size, mobile phase composition and chamber-saturation time were critically studied, and the optimum conditions were selected. A satisfactory resolution (Rs = 2.67) with RF 0.48 and 0.69 and high sensitivity with limits of detection of 4 and 7 ng/band for FEB and DIC, respectively, were obtained. In addition, derivative ratio and ratio difference spectrophotometric methods were established for the analysis of such a mixture. All methods were validated as per the ICH guidelines. In the HPTLC method, the calibration plots were linear between 0.01-0.55 and 0.02-0.60 µg/band, for FEB and DIC, respectively. For the spectrophotometric methods, the calibration graphs were linear between 2-14 and 4-18 µg/mL for FEB and DIC, respectively. The simplicity and specificity of the proposed methods suggest their application in quality control analysis of FEB and DIC in their raw materials and tablets. A comparison of the proposed methods with the existing methods is presented.

The effect of a bioglass paste on enamel exposed to erosive challenge.

OBJECTIVES: The current study is evaluating the effect of using a 45S5 bioglass paste and topical fluoride application on the cross sectional micro-hardness and the chemical surface changes of eroded enamel. METHODS: Enamel discs were obtained from the buccal surface of one hundred extracted human non-carious third molars. The enamel surfaces were ground flat and each disc was coated with two layers of acid resistant nail varnish except for an exposed treatment window (3mm×2mm) on the buccal surface of the tooth. All specimens were challenged for 60 min by orange juice (Tropicana, Chicago, USA) pH 3.85+0.5. The specimens were divided into four groups: the 45S5 bioglass paste group, fluoride gel group (5 min application), fluoride gel group (24h application) while the rest of specimens served as control. The cross-sectional micro-hardness of 20 specimens from each group was measured. Five specimens from each group had their top eroded enamel surfaces examined by SEM-EDS. One-way ANOVA was used to compare the cross-sectional micro-hardness of the three groups p<0.05. RESULTS: 45S5 bioglass paste application significantly improved the sub-surface eroded enamel when compared to fluoride and control specimens (p<0.05). CONCLUSION: 45S5 bioglass paste can efficiently improve the micro-hardness of the sub-surface eroded enamel surface. CLINICAL SIGNIFICANCE: The use of the 45S5 Bioglass paste can be used efficiently as a potent remineralizing agent for the sub-surface enamel lesions resulting from erosive challenges.