RESUMEN
Background and objective Recent studies have challenged the notion that prolonged intravenous (IV) antibiotics are preferable to oral antibiotics for treating musculoskeletal infections. Our institution's orthopedic surgery and orthopedic infectious disease (ID) groups have established consensus criteria for the use of oral antibiotics in musculoskeletal infections. In this study, we examine one-year and two-year outcomes of the selective use of oral antibiotics for musculoskeletal infections in a real-world setting. Methods We conducted a single-center retrospective analysis of adults seen in our orthopedic ID clinic over a six-month period for the first episode of surgically managed osteomyelitis, native joint septic arthritis (NJSA), prosthetic joint infection (PJI), or other musculoskeletal hardware infection with an established microbiologic etiology who received surgical interventions and >2 weeks of antimicrobial treatment. Patients were evaluated for treatment failure at one year and two years following their index surgery, which we defined as death, unplanned surgery, or the initiation of chronic antibiotic suppression. Results One-year treatment failure rates were 0/23 (0%) in patients who switched to oral therapy versus 6/17 (35%) in patients who remained on IV treatment. Two-year treatment failure rates were 0/23 (0%) in patients who switched to oral therapy versus 8/17 (47%) in patients who remained on IV treatment. Conclusions Our consensus criteria for the switch to oral antibiotics for musculoskeletal infections identified patients who went on to have excellent outcomes at one year and two years, suggesting that these criteria can effectively identify patients at low risk for treatment failure. Collaboration between ID specialists and orthopedic surgeons to select antimicrobial regimens can avoid significant burdens, costs, and complications associated with prolonged IV therapy.
RESUMEN
Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in humans, yet the molecular etiology is currently unknown. Evidence suggests that genetic factors may play an important role in some cases of idiopathic BPPV, particularly in familial cases, but the responsible genetic variants have not been identified. In this study, we performed whole exome sequencing [including untranslated regions (UTRs)] of 12 families and Sanger sequencing of additional 30 families with recurrent BPPV in Caucasians from the United States (US) Midwest region, to identify the genetic variants responsible for heightened susceptibility to BPPV. Fifty non-BPPV families were included as controls. In silico and experimental analyses of candidate variants show that an insertion variant rs113784532 (frameshift causing truncation) in the neural cadherin gene PCDHGA10 (protocadherin-gamma A10) is an exceedingly strong candidate (p = 1.80x10-4 vs. sample controls; p = 5.85x10-19 vs. ExAC data; p = 4.9x10-3 vs. NHLBI exome data). The mutant protein forms large aggregates in BPPV samples even at young ages, and affected subjects carrying this variant have an earlier onset of the condition than those without [average 44.0±14.0 (n = 16) versus 54.4±16.1 (n = 36) years old, p = 0.054]. In both human and mouse inner ear tissues, PCDHGA10 is expressed in ganglia, hair cells and vestibular transitional epithelia. Fluorescent RNA in situ hybridization using mouse inner ear tissues shows that expression increases with age. In summary, our data show that a variant in the PCDHGA10 gene may be involved in causing or aggravating some familial cases of recurrent idiopathic BPPV.
