Development and Validation of the Foot Union Scoring Evaluation Tool for Arthrodesis of Foot Structures.

Reliable evaluation of osseous consolidation after pedal arthrodesis can be difficult, and the presence or absence of radiographic healing often dictates care. Plain radiographs remain the mainstay imaging tool owing to their cost, efficiency, and low radiation exposure. Applying radiographic parameters that can reliably determine osseous healing is essential. However, currently, no reliable or validated measures are available to determine osseous union of any joint in the foot or ankle. The purpose of the present study was to develop a radiographic healing scoring system that would enhance the diagnostic healing assessment after joint arthrodesis of the foot or ankle. We adapted several existing scales previously validated for fracture healing in the leg, because no study has attempted to apply this to a joint fusion model. A total of 150 cases were evaluated by 6 blinded assessors to test the interrater reliability of the subjective healing assessment compared with the proposed scoring system. The radiographs were classified by the postoperative period: ≤4 weeks, 5 to 12 weeks, and >12 weeks. The initial proposed scale was found to have high interrater reliability but was burdensome. Using a priori item reduction protocols, a limited 5-item scale further improved the internal consistency and reduced the burden. The result was excellent interrater reliability (α = 0.978, standard deviation 0.02, 95% confidence interval 0.96 to 0.99) among all assessors compared with the reduced reliability (α = 0.752) for subjective arthrodesis healing. Intrarater reliability was also found to be superior using a test-retest method. The reliability of this system appeared superior to the subjective assessment of arthrodesis healing, even in the absence of clinical correlates, after foot arthrodesis.

Radiographic Union Scoring Scale for Determining Consolidation Rates in the Calcaneus.

The reliable evaluation of osseous consolidation after hindfoot osteotomy can be difficult. Concomitant hindfoot osteotomies often dictate the advancement of weightbearing, and radiographs are the mainstay imaging tool owing to cost, efficiency, and radiation exposure. Understanding the radiographic parameters that can be used to reliably determine osseous healing is paramount. However, currently, no reliable or validated method is available to determine osseous healing of hindfoot osteotomies in irregular bones of the foot. The purpose of the present study was to develop a radiographic healing scoring system that would enhance the diagnostic healing assessment after elective calcaneal osteotomy. We adapted existing orthopedic scales validated for healing in the leg for application in the irregular bones of the foot. A total of 168 cases were evaluated by 6 blinded assessors to test the interrater reliability of subjective healing assessment compared with the proposed scoring system. The radiographs were classified by postoperative period: ≤4 weeks, 5 to 12 weeks, and >12 weeks. The proposed scale had high interrater reliability but was burdensome. Using a priori item reduction protocols, a limited 6-item scale further improved internal consistency and reduced the burden. The result was excellent interrater reliability (α = 0.98, standard deviation 0.02, 95% confidence interval 0.91 to 0.96) among all assessors when using the scoring scale compared with unacceptable reliability (α = 0.438) for subjective osteotomy healing. The reliability of our system appeared superior to that of subjective assessment of osseous healing alone, even in the absence of clinical correlates after osteotomy of the calcaneus.

Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro.

BACKGROUND: Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 microM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC50), cytotoxicity (CC50) and the in vitro therapeutic index in live virus and pseudotype assay formats. RESULTS: While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. CONCLUSION: All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.

Simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy.

Nipah (NiV) and Hendra (HeV) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. We designed a new high-throughput screening (HTS) assay for inhibitors of infection based on envelope glycoprotein pseudotypes. The assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral life cycle, but it still can be carried out under biosafety level 2 (BSL-2) conditions. These features permit a screen for antivirals for emerging viruses and select agents that otherwise would require BSL-4 HTS facilities. The screening of a small compound library identified several effective molecules, including the well-known compound chloroquine, as highly active inhibitors of pseudotyped virus infection. Chloroquine inhibited infection with live HeV and NiV at a concentration of 1 microM in vitro (50% inhibitory concentration, 2 microM), which is less than the plasma concentrations present in humans receiving chloroquine treatment for malaria. The mechanism for chloroquine's antiviral action likely is the inhibition of cathepsin L, a cellular enzyme that is essential for the processing of the viral fusion glycoprotein and the maturation of newly budding virions. Without this processing step, virions are not infectious. The identification of a compound that inhibits a known cellular target that is important for viral maturation but that had not previously been shown to have antiviral activity for henipaviruses highlights the validity of this new screening assay. Given the established safety profile and broad experience with chloroquine in humans, the results described here provide an option for treating individuals infected by these deadly viruses.