An overview of risk factors, management and prevention of cochlear implant infections.

PURPOSE OF REVIEW: With cochlear implantation becoming increasingly performed worldwide, an understanding of the risk factors, preventive measures, and management of cochlear implant (CI) infection remains important given the significant morbidity and cost it conveys. RECENT FINDINGS: At the turn of the 21st century there was a decrease in rates of CI infection, particularly meningitis, following the discontinuation of positioner use for CI. However, in more recent years rates of CI infection have remained largely static. Recently, studies evaluating preventive measures such as pneumococcal vaccination, S. aureus decolonization and surgical antibiotic prophylaxis have emerged in the literature. SUMMARY: Prompt recognition of CI infection and appropriate investigation and management are key, however at present treatment is largely informed by cohort and case-control studies and expert opinion. Preventive measures including pneumococcal vaccination, S. aureus decolonization and preoperative antibiotic prophylaxis play a role in reducing rates of CI infection. However, there remains a need for well designed clinical trials to provide higher level evidence to better guide preventive measures for, and management decisions of, CI infections in the future.

Cellulitis in children: a retrospective single centre study from Australia.

Aim: To characterise the epidemiology, clinical features and treatment of paediatric cellulitis. Methods: A retrospective study of children presenting to a paediatric tertiary hospital in Western Australia, Australia in 2018. All inpatient records from 1 January to 31 December 2018 and emergency department presentations from 1 July to 31 December 2018 were screened for inclusion. Results: 302 episodes of cellulitis were included comprising 206 (68.2%) admitted children and 96 (31.8%) non-admitted children. The median age was 5 years (IQR 2-9), 40 (13.2%) were Aboriginal and 180 (59.6%) boys. The extremities were the most commonly affected body site among admitted and non-admitted patients. There was a greater proportion of facial cellulitis in admitted patients (27.2%) compared with non-admitted patients (5.2%, p<0.01). Wound swab was the most frequent microbiological investigation (133/302, 44.0%), yielding positive cultures in the majority of those tested (109/133, 82.0%). The most frequent organisms identified were Staphylococcus aureus (94/109, 86.2%) (methicillin-susceptible S. aureus (60/94, 63.8%), methicillin-resistant S. aureus) and Streptococcus pyogenes (22/109, 20.2%) with 14 identifying both S. aureus and S. pyogenes. Intravenous flucloxacillin was the preferred antibiotic (154/199, 77.4%), with median intravenous duration 2 days (IQR 2-3), oral 6 days (IQR 5-7) and total 8 days (IQR 7-10). Conclusions: Cellulitis is a common reason for presentation to a tertiary paediatric hospital. We confirm a high prevalence of extremity cellulitis and demonstrate that children with facial cellulitis often require admission. Cellulitis disproportionately affected Aboriginal children and children below 5 years. Prevention of cellulitis involves early recognition and treatment of skin infections such as impetigo and scabies.

Exploring genotype-phenotype relationships in the CDKL5 deficiency disorder using an international dataset.

Characterized by early-onset seizures, global developmental delay and severe motor deficits, CDKL5 deficiency disorder is caused by pathogenic variants in the cyclin-dependent kinase-like 5 gene. Previous efforts to investigate genotype-phenotype relationships have been limited due to small numbers of recurrent mutations and small cohort sizes. Using data from the International CDKL5 Disorder Database we examined genotype-phenotype relationships for 13 recurrent CDKL5 variants and the previously analyzed historic variant groupings. We have applied the CDKL5 Developmental Score (CDS) and an adapted version of the CDKL5 Clinical Severity Assessment (CCSA), to grade the severity of phenotype and developmental outcomes for 285 individuals with CDKL5 variants. Comparisons of adapted CCSA and CDS between recurrent variants and variant groups were performed using multiple linear regression adjusting for age and sex. Individuals with the missense variant, p.Arg178Trp, had the highest mean adapted CCSA and lowest mean developmental scores. Other variants producing severe phenotypes included p.Arg559* and p.Arg178Gln. Variants producing milder phenotypes included p.Arg134*, p.Arg550*, and p.Glu55Argfs*20. There are observed differences in phenotype severity and developmental outcomes for individuals with different CDKL5 variants. However, the historic variant groupings did not seem to reflect differences in phenotype severity or developmental outcomes as clearly as analyzed by individual variants.

Expanding the phenotype of the CDKL5 deficiency disorder: Are seizures mandatory?

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene cause the neurodevelopmental disorder, the CDKL5 deficiency disorder. Reports of individuals with pathogenic variants in CDKL5 without seizures are exceedingly rare, and in-depth analyses of their variants have been lacking. Whole-genome sequencing was performed on a 29-year-old female with mild intellectual disability who, in the absence of overt seizures, presented with multiple episodes of altered mental status over a 24-year period. Clinical history was supplemented by a parent completed questionnaire from the International CDKL5 Disorder Database. We identified a de novo heterozygous variant in CDKL5 (NM_003159.2:c.645T>A;p.Ser215Arg). In-depth computational analysis performed to predict the impact of the variant on protein structure and function demonstrated that the variant was likely pathogenic. In this light, cell-based studies showed that the S215R substitution causes a marked reduction in CDKL5 kinase activity. Similarities between our case and one previously reported case are striking. These cases, both without seizures but with apparent behavioral symptomatology, together question whether seizures are mandatory in this neurodevelopmental disorder.