Background: Acute septic arthritis (SA) still remains a challenge with significant worldwide morbidity. In recent years, Kingella kingae has emerged and treatment regimens have become shorter. We aim to analyze trends in SA etiology and management and to identify risk factors for complications. Methods: Longitudinal observational, single center study of children (<18 years old) with SA admitted to a tertiary care pediatric hospital, from 2003 to 2018, in 2 cohorts, before and after implementation of nucleic acid amplification assays (2014). Clinical, treatment and disease progression data were obtained. Results: A total of 247 children were identified, with an average annual incidence of 24.9/100,000, 57.9% males with a median age of 2 (1-6) years. In the last 5 years, a 1.7-fold increase in the annual incidence, a lower median age at diagnosis and an improved microbiologic yield (49%) was noticed. K. kingae became the most frequent bacteria (51.9%) followed by MSSA (19.2%) and S. pyogenes (9.6%). Children were more often treated for fewer intravenous days (10.7 vs. 13.2 days, P = 0.01) but had more complications (20.6% vs. 11.4%, P = 0.049) with a similar sequelae rate (3.7%). Risk factors for complications were C-reactive protein ≥80 mg/L and Staphylococcus aureus infection, and for sequelae at 6 months, age ≥4 years and CRP ≥ 80 mg/L. Conclusions: The present study confirms that K. kingae was the most common causative organism of acute SA. There was a trend, although small, for decreasing antibiotic duration. Older children with high inflammatory parameters might be at higher risk of sequelae.

This study emphasises the value of a systematic articular examination of joints in KD. Refractory KD was observed in children with late-onset arthritis.

In just over a decade, advances in genome-wide association studies (GWAS) have offered an approach to stratify individuals based on genetic risk for disease. Using recent Alzheimer's disease (AD) GWAS results as the base data, we determined each individual's polygenic risk score (PRS) in the UK Biobank dataset. Using individuals within the extreme risk distribution, we performed a GWAS that is agnostic of AD phenotype and is instead based on known genetic risk for disease. To interpret the functions of the new risk factors, we conducted phenotype analyses, including a phenome-wide association study. We identified 246 loci surpassing the significance threshold of which 229 were not reported in the base AD GWAS. These include loci that showed suggestive levels of association in the base GWAS and loci not previously suspected to be associated with AD. Among these, there are loci, such as IL34 and KANSL1, that have since been shown to be associated with AD in recent studies. We also show highly significant genetic correlations with multiple health-related outcomes that provide insights into prodromal symptoms and comorbidities. This is the first study to utilize PRS as a phenotype-agnostic group classification in AD genetic studies. We identify potential new loci for AD and detail phenotypic analysis of these PRS extremes.

Linezolid has been used in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis in adults with encouraging results, however experience in children is scarce. We describe our experience with the use of linezolid as part of a multidrug regimen in the treatment of 4 patients who had persistent positive cultures, despite prolonged combined therapy.