Evolving Threat of Community Acquired Methicillin Resistant Staphylococcus aureus Upper Extremity Infections in the South Pacific: 2011-2015.

Background: Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA) rates have been increasing worldwide and contribute to a growing "global health security threat" as reported by the WHO. Our group previously reported an overall rate of 7% in CA-MRSA upper extremity infections between 2004-2009 at the Auckland Regional Hand Unit. This fell below the Center for Disease Control (CDC) recommendation for empiric antimicrobial cover once local rates exceed 10-15%. We examined prevalence and characteristics of CA-MRSA upper extremity infections in our region over a subsequent 5-year period. Methods: One thousand two hundred and fifty-two patients with upper extremity infections requiring operative management between 2011 and 2015 inclusive were included in this study. Associated clinical characteristics were recorded including ethnicity, cultured organisms, antibiotic sensitivities, infection rate, and treatment practice. Results: One hundred and fifty (12%) of patients had culture positive CA-MRSA upper extremity infections. There was an increasing annual trend. Of note, rates of CA-MRSA in the Maori and Pacific Island ethnic subpopulations exceeded 15% in 2014 and 2015. Susceptibilities, associated factors and patient demographics are reported. Conclusions: Our unit enjoys significantly lower rates of CA-MRSA upper extremity infections than has been reported internationally. However, trends are increasing relative to our prior 6-year report, and the threshold for empiric treatment has been met within the Maori and Pacific Island ethnic subpopulations. This evolving threat is also highlighted by increasing cases of multi-drug resistant CA-MRSA. Evolving regional guidelines for empiric coverage of CA-MRSA among high-risk ethnic subpopulations identified by this study are underway.

Laterally Dispersing Nozzles for Needle-assisted Jet Injection.

Most transdermal drug delivery systems are designed to inject drugs through the skin in a direction normal to the skin surface. However, in some applications, such as local anaesthesia, it is desirable to disperse the drug in a direction parallel to the surface of the skin. In this paper we present nozzles for needle-assisted jet injection that are designed to laterally disperse the fluid drug at a chosen depth in tissue. These nozzles were manufactured by laser machining holes in the walls of 0.57 mm (24 G) hypodermic needles, and sealing the ends of the needles. An existing controllable jet injection system was used to test the nozzles. High-speed video recordings were taken to examine the shape of the high-speed jets emitted from the orifices, and jet injections into post mortem porcine tissue were performed to evaluate the resulting dispersion pattern. These injections demonstrated the ability of these nozzles to achieve a widely spread dispersion at a depth of 3 mm to 4 mm in tissue. We observed that the widest dispersion occurred at the same depth as the orifices, and dispersion was greater in the direction of the jets. Further investigation, including an in vivo study, is now required to evaluate whether this technique can reduce the time, cost or pain associated with transdermal local anaesthetic delivery.

Next-generation sequencing targeted disease panel in rod-cone retinal dystrophies in Maori and Polynesian reveals novel changes and a common founder mutation.

IMPORTANCE: This study identifies unique genetic variation observed in a cohort of Maori and Polynesian patients with rod-cone retinal dystrophies using a targeted next-generation sequencing retinal disease gene panel. BACKGROUND: With over 250 retinal disease genes identified, genetic diagnosis is still only possible in 60-70% of individuals and even less within unique ethnic groups. DESIGN: Prospective genetic testing in patients with rod-cone retinal dystrophies identified from the New Zealand Inherited Retinal Disease Database, PARTICIPANTS: Sixteen patients of Maori and Polynesian ancestry. METHODS: Next-generation sequencing of a targeted retinal gene panel. Sanger sequencing for a novel PDE6B mutation in subsequent Maori patients. MAIN OUTCOME MEASURES: Genetic diagnosis, genotype-phenotype correlation. RESULTS: Thirteen unique pathogenic variants were identified in 9 of 16 (56.25%) patients in 10 different genes. A definitive genetic diagnosis was made in 7/16 patients (43.7%). Six changes were novel and not in public databases of human variation. In four patients, a homozygous, novel pathogenic variant (c.2197G > C, p.(Ala 733Pro)) in PDE6B was identified and also present in a further five similarly affected Maori patients. CONCLUSIONS AND RELEVANCE: Over half of the Maori and Polynesian patients with inherited rod-cone diseases have no pathogenic variant(s) detected with a targeted retinal next-generation sequencing strategy, which is supportive of novel genetic mechanisms in this population. A novel PDE6B founder variant is likely to account for 16% of recessive inherited retinal dystrophy in Maori. Careful characterization of the clinical presentation permits identification of further Maori patients with a similar phenotype and simplifies the diagnostic algorithm.

In vivo confocal microscopy analyses of corneal microstructural changes in a prospective study of collagen cross-linking in keratoconus.

PURPOSE: To use in vivo confocal microscopy (IVCM) to quantitatively analyze microstructural changes over time, after corneal collagen cross-linking for keratoconus. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 38 eyes of 38 patients undergoing collagen cross-linking for keratoconus. METHODS: Prospective, clinical cohort study of corneal collagen cross-linking in progressive keratoconus. Laser scanning IVCM performed preoperatively and at 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Density of corneal sub-basal nerves, anterior and posterior keratocytes, and corneal endothelium. RESULTS: Compared with baseline values, the mean sub-basal nerve density decreased significantly at 1, 3, and 6 months postoperatively (P < 0.01); however, this returned to preoperative values at 12 months (P = 0.57). One month postoperatively, there was complete absence of keratocyte nuclei in 86% of corneas. Anterior stromal edema with hyper-reflective cytoplasm and extracellular lacunae in a honeycomb-like appearance was observed and persisted at 3 months postoperatively. Scattered, presumed fragmented keratocyte nuclei, were observed at 1 and 3 months, but by 6 months, keratocyte repopulation of the anterior stroma was apparent. Quantitative analysis confirmed a significant decrease in the mean anterior keratocyte density 1, 3, and 6 months postoperatively (P ≤ 0.01) with return to baseline values at 12 months postoperatively (P = 0.57). The demarcation between treated and untreated corneal stroma appeared as a region where normal keratocytes transitioned into elongated, hyper-reflective, needle-like structures and then into large hyper-reflective stromal bands. There was no significant change in posterior keratocyte density or endothelial density at any postoperative time point. CONCLUSIONS: This prospective IVCM study revealed complete loss of the sub-basal nerve plexus and loss of anterior stromal keratocytes in the early postoperative period, with complete regeneration of the sub-basal nerve plexus and keratocyte repopulation by 12 months postoperatively. The posterior stroma and corneal endothelium were unaffected.