Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review.

BACKGROUND: Ototoxicity has been reported after administration of aminoglycosides and glycopeptides. OBJECTIVES: To identify available evidence for the occurrence and determinants of aminoglycoside- and glycopeptide-related ototoxicity in children. MATERIALS AND METHODS: Systematic electronic literature searches that combined ototoxicity (hearing loss, tinnitus and/or vertigo) with intravenous aminoglycoside and/or glycopeptide administration in children were performed in PubMed, EMBASE and Cochrane Library databases. Studies with sample sizes of ≥50 children were included. The QUIPS tool and Cochrane criteria were used to assess the quality and risk of bias of included studies. RESULTS: Twenty-nine aminoglycoside-ototoxicity studies met the selection criteria (including 7 randomized controlled trials). Overall study quality was medium/low. The frequency of hearing loss within these studies ranged from 0%-57%, whereas the frequency of tinnitus and vertigo ranged between 0%-53% and 0%-79%, respectively. Two studies met the criteria on glycopeptide-induced ototoxicity and reported hearing loss frequencies of 54% and 55%. Hearing loss frequencies were higher in gentamicin-treated children compared to those treated with other aminoglycosides. In available studies aminoglycosides had most often been administered concomitantly with platinum agents, diuretics and other co-medication. CONCLUSIONS: In children the reported occurrence of aminoglycoside/glycopeptide ototoxicity highly varies and seems to depend on the diagnosis, aminoglycoside subtype and use of co-administered medication. More research is needed to investigate the prevalence and determinants of aminoglycoside/glycopeptide ototoxicity. Our results indicate that age-dependent audiological examination may be considered for children frequently treated with aminoglycosides/glycopeptides especially if combined with other ototoxic medication.

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

On the flow dependency of the electrical conductivity of blood.

Experiments presented in the literature show that the electrical conductivity of flowing blood depends on flow velocity. The aim of this study is to extend the Maxwell-Fricke theory, developed for a dilute suspension of ellipsoidal particles in an electrolyte, to explain this flow dependency of the conductivity of blood for stationary laminar flow in a rigid cylindrical tube. Furthermore, these theoretical results are compared to earlier published measurement results. To develop the theory, we assumed that blood is a Newtonian fluid and that red blood cells can be represented by oblate ellipsoids. If blood flows through a cylindrical tube, shear stresses will deform and align the red blood cells with one of their long axes aligned parallel to the stream lines. The pathway of a low-frequency (< 1 MHz) alternating electrical current will be altered by this orientation and deformation of the red blood cells. Consequently, the electrical conductivity in the flow direction of blood increases. The theoretically predicted flow dependency of the conductivity of blood corresponds well with experimental results. This theoretical study shows that red blood cell orientation and deformation can explain quantitatively the flow dependency of blood conductivity.

Imaging of thoracic blood volume changes during the heart cycle with electrical impedance using a linear spot-electrode array.

Electrical impedance (EI) measurements conducted on the thorax contain useful information about the changes in blood volume that occur in the thorax during the heart cycle. The aim of this paper is to present a new (tomographic-like) method to obtain this relevant information with electrical impedance measurements, using a linear electrode array. This method is tested on three subjects and the results are compared with results, obtained from magnetic resonance cine-images showing the cross-sectional surface area changes of the aorta, the vena cava, the carotid arteries, and the heart. This paper shows that the different sources of the thoracic EI waveform may be separated in time and location on the thoracic surface and that aortic volume changes may be estimated accurately.

Comparing spot electrode arrangements for electric impedance cardiography.

This study investigates whether an arrangement with nine spot electrodes, for thoracic bio-impedance cardiography, can be replaced by an arrangement with five spot electrodes. The study was conducted on 15 healthy subjects, six females and nine males, in supine rest. The variables obtained from the measurements were the mean of the impedance of the thorax segment between the recording electrodes, the maximum negative deflection of the first derivative of the thoracic impedance, the left ventricular ejection time and an estimate of left ventricular stroke volume. An analysis of variance for a randomized complete block design was used to determine whether significant differences exist in the group means of the observed variables between six different electrode arrangements. If no statistically significant differences were found in these group means between pairs of arrangements, Bland and Altman analyses were used to determine the differences in the observed variables between pairs of arrangements for individual subjects. This study concludes that reducing the number of spot electrodes from nine to five, does not yield significant differences in the group means of the observed variables, but it could result in large differences in the values of these variables for individual subjects.