Comparison of TIVA with different combinations of ketamine–propofol mixtures in pediatric patients

Abstract

Purpose

Adding ketamine to propofol has been suggested to be useful for sedation and general anesthesia. This study aimed to determine the effect of TIVA with different ratios of ketofol on recovery in children.

Methods

Seventy-five children aged 3–12 years and undergoing adenoidectomy and/or tonsillectomy surgery were randomized into three groups. Ratios of 1:5, 1:6.7 and 1:10 ketamine–propofol mixture (ketofol) were prepared in the same syringe for groups I, II and III, respectively. Induction and maintenance of anesthesia were performed with 1:5, 1:6.7 and 1:10 ratios of ketofol in groups I, II and III, respectively. A McFarlan infusion dose regimen was used (15 mg/kg/h for 15 min, 13 mg/kg/h for 15 min, 11 mg/kg/h for 30 min) and infusion rates were decreased for the different ratios. Infusion rates were reduced to 67, 80 and 90% of the McFarlan dose regimen for groups I, II and III, respectively. Extubating time, length of stay in PACU, postoperative PAED and FLACC scores were recorded.

Results

Extubating time was significantly lower [mean 254.3 ± 92.7 s (95% CI 216.6–292.6, p = 0.001)] in group III than in groups I and II [371.3 ± 153 s (308.1–434.48) and 343.2 ± 123.7 s (292.2–394.3), respectively]. Length of stay in the PACU was lower in group III [median 15 min (interquartile range 15–20, p = 0.001)] than in groups I and II: 20 (15–27.5) and 20 min (20–27.5), respectively.

Conclusion

TIVA with a 1:10 ratio of ketofol admixture with a 90% reduction of McFarlan regimen can provide improved recovery conditions.

Trial registration

ClinicalTrials.gov identifier: NCT02848963.

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Human c-SRC kinase (CSK) overexpression makes T cells dummy

Abstract

Adoptive cell therapy with T-cell receptor (TCR)-engineered T cells represents a powerful method to redirect the immune system against tumours. However, although TCR recognition is restricted to a specific peptide–MHC (pMHC) complex, increasing numbers of reports have shown cross-reactivity and off-target effects with severe consequences for the patients. This demands further development of strategies to validate TCR safety prior to clinical use. We reasoned that the desired TCR signalling depends on correct pMHC recognition on the outside and a restricted clustering on the inside of the cell. Since the majority of the adverse events are due to TCR recognition of the wrong target, we tested if blocking the signalling would affect the binding. By over-expressing the c-SRC kinase (CSK), a negative regulator of LCK, in redirected T cells, we showed that peripheral blood T cells inhibited anti-CD3/anti-CD28-induced phosphorylation of ERK, whereas TCR proximal signalling was not affected. Similarly, overexpression of CSK together with a therapeutic TCR prevented pMHC-induced ERK phosphorylation. Downstream effector functions were also almost completely blocked, including pMHC-induced IL-2 release, degranulation and, most importantly, target cell killing. The lack of effector functions contrasted with the unaffected TCR expression, pMHC recognition, and membrane exchange activity (trogocytosis). Therefore, co-expression of CSK with a therapeutic TCR did not compromise target recognition and binding, but rendered T cells incapable of executing their effector functions. Consequently, we named these redirected T cells "dummy T cells" and propose to use them for safety validation of new TCRs prior to therapy.

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Factors impacting hearing aid performance outcomes for Egyptian hearing impaired children

Publication date: Available online 15 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Eman Abdel-Fattah Said
Despite recent technological advances in the audiologic assessment of children, their hearing aid fitting remains a daunting task.Aims of studyTo assess effectiveness of amplification in children using aided sound field tests and Auditory Behavior in Everyday Life (ABEL) questionnaire and to elucidate factors contributing to poor outcomes.MethodsDetailed medical history, otoscopic examination, basic audiological evaluation, aided sound field tests and ABEL questionnaire for 114 hearing impaired children aged 4–16 years.ResultsCongenital HL considered the commonest cause of HL (55.3%), 36% had unknown cause and 8.8% of HI had acquired cause. Profound loss in 67.5%, severe in 17% and 54.4% of them (54.4%) were fitted around the age of 3 years. Binaural HA in 88.6% and digital type for 61.4%. There were statistically significant differences between unaided and aided values in sound field tests for HI children.Poor performance in direct measures and ABEl in children with congenital and profound degree of hearing loss, better response when they were fitted earlier with digital aids. ABEL scores showed negative correlations with aided tonal sound field test and positive with aided speech discrimination score.ConclusionsInappropriate amplification, late age of fitting with no speech therapy were clinical red flags for poor outcomes. ABEL questionnaire was a valid procedure to assess the hearing aids appropriateness.



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Childhood hearing loss is a key feature of CAPOS syndrome: A case report

Publication date: January 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 104
Author(s): Stéphanie Paquay, Elsa Wiame, Naima Deggouj, Antonella Boschi, Romolo Daniele De Siati, Yves Sznajer, Marie-Cécile Nassogne
CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) is a rare neurological disorder, recently associated with the c.2452G > A hotspot mutation in the ATP1A3 gene, with sensorineural hearing loss as a prominent feature. We herein report on a girl who has experienced hearing loss for three years following an initial encephalitic episode when aged 15 months old. CAPOS was diagnosed only when she was six years old by targeted testing whilst she displayed optic atrophy, cerebellar signs and areflexia. CAPOS syndrome should be considered in the differential diagnosis of acquired childhood deafness, prompting clinicians to search for associated neurological features.



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Genetic analysis of CLDN14 in the Chinese population affected with non-syndromic hearing loss

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Yajie Lu, Jun Yao, Qinjun Wei, Jin Xu, Guangqian Xing, Xin Cao
ObjectiveThe CLDN14 gene, encoding the tight junction protein Claudin-14, has been proposed as a candidate causative gene affecting autosomal recessive non-syndromic hearing loss (ARNSHL). Genetic analysis of nonsynonymous single-nucleotide variations (nsSNVs) in CLDN14 has been performed in different populations. The role of CLDN14 nsSNVs in contributing to hearing loss in Chinese populations would be investigated in this study.MethodsTarget screening for CLDN14 variations were conducted in 500 unrelated patients diagnosed with non-syndromic hearing loss (NSHL).ResultsNo reported pathogenic CLDN14 nsSNVs in heterozygote or homozygote were detected in this study, however, we identified 4 heterozygous nsSNVs [c.11C > T, p.(Thr4Met); c.16G > A, p.(Val6Met); c.68T > C, p.(Ile23Thr); c.367A > C, p.(Thr123Pro)] in CLDN14. The 4 nsSNVs are located at claudin-14 transmembrane domains, but assessed to be poorly conservative and non-pathogenic via multiple in silico algorithms. The structure-based analysis also suggested that the 4 nsSNVs had less structural and functional impact on claudin-14.ConclusionOur findings indicated that CLDN14 might not be a major causative gene for NSHL in Chinese populations, which would contribute to fully understanding the genetic cause of NSHL in the East Asian populations.



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SLC52A2 mutations cause SCABD2 phenotype: A second report

Publication date: January 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 104
Author(s): Mojgan Babanejad, Omid Ali Adeli, Nooshin Nikzat, Maryam Beheshtian, Hakimeh Azarafra, Farnaz Sadeghnia, Marzieh Mohseni, Hossein Najmabadi, Kimia Kahrizi
IntroductionAutosomal recessive cerebellar ataxias (ARCAs) are a large group of neurodegenerative disorders that manifest mainly in children and young adults. Most ARCAs are heterogeneous with respect to age at onset, severity of disease progression, and frequency of extracerebellar and systemic signs.MethodsThe phenotype of a consanguineous Iranian family was characterized using clinical testing and pedigree analysis. Whole-exome sequencing was used to identify the disease-causing gene in this family.Results and conclusionUsing whole exome sequencing (WES), a novel missense mutation in SLC52A2 gene is reported in a consanguineous Iranian family with progressive severe hearing loss, optic atrophy and ataxia. This is the second report of the genotype-phenotype correlation between this syndrome named spinocerebellar ataxia with blindness and deafness type 2 (SCABD2) and SLC52A2 gene.



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Pediatric Meniere's disease

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Chi Wang, Chien-Hao Wu, Po-Wen Cheng, Yi-Ho Young
ObjectiveThis study adopted an inner ear test battery comprising audiometry, and ocular vestibular evoked myogenic potential (oVEMP), cervical VEMP (cVEMP), and caloric tests to investigate the sequence of inner ear deficits in pediatric Meniere's disease (MD).MethodsFrom 2005 to 2016, a total of 24 MD children aged <15 years old underwent otoscopy, CT scan, blood test, and an inner ear test battery. Nine subjects were males and 15 were females, with mean age of 12 years. Right ear was affected in 3 patients, left ear in 5 patients, and both ears in 16 patients (67%). Eight (33%) of the 24 MD children had positive family history.ResultsInner ear deficits in MD children ran from abnormal hearing (25%) to abnormal cVEMP (20%), oVEMP (13%), and caloric (12%) tests, exhibiting a significantly declining sequence from the cochlea, to the saccule, utricle and semicircular canals. Analysis between the laterality and family history revealed a significantly positive correlation.ConclusionPediatric MD is rare, accounting for 2.3% prevalence in MD patients. The inner ear deficits in pediatric MD showed a significantly declining sequence from the cochlea, to the saccule, utricle and semicircular canals, mimicking the sequence in adult MD. One-third MD children had positive family history, which may explain the high rate of bilateral affliction and symmetrical hearing levels on both ears.



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