A new lineage nomenclature to aid genomic surveillance of dengue virus.

Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.

Blockade of dengue virus transmission from viremic blood to Aedes aegypti mosquitoes using human monoclonal antibodies.

BACKGROUND: Dengue is the most prevalent arboviral disease of humans. Virus neutralizing antibodies are likely to be critical for clinical immunity after vaccination or natural infection. A number of human monoclonal antibodies (mAbs) have previously been characterized as able to neutralize the infectivity of dengue virus (DENV) for mammalian cells in cell-culture systems. METHODOLOGY/PRINCIPLE FINDINGS: We tested the capacity of 12 human mAbs, each of which had previously been shown to neutralize DENV in cell-culture systems, to abrogate the infectiousness of dengue patient viremic blood for mosquitoes. Seven of the twelve mAbs (1F4, 14c10, 2D22, 1L12, 5J7, 747(4)B7, 753(3)C10), almost all of which target quaternary epitopes, inhibited DENV infection of Ae. aegypti. The mAbs 14c10, 747(4)B7 and 753(3)C10 could all inhibit transmission of DENV in low microgram per mL concentrations. An Fc-disabled variant of 14c10 was as potent as its parent mAb. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that mAbs can neutralize infectious DENV derived from infected human cells, in the matrix of human blood. Coupled with previous evidence of their ability to prevent DENV infection of mammalian cells, such mAbs could be considered attractive antibody classes to elicit with dengue vaccines, or alternatively, for consideration as therapeutic candidates.

Predictors of Mortality from Spontaneous Soft-Tissue Hematomas in a Large Multicenter Cohort Who Underwent Percutaneous Transarterial Embolization.

Purpose To evaluate the safety and efficacy of percutaneous transarterial embolization (PTAE) for the treatment of spontaneous soft-tissue hematomas (SSTHs) and identify variables predictive of short-term outcome. Materials and Methods Between 2011 and 2017, the outcome was retrospectively analyzed for 112 patients (mean age ± standard deviation, 72 years ± 14; range, 28-92 years), including 65 women (mean age, 73 years ± 12.7; range, 39-92 years) and 47 men (mean age, 70 years ± 14.9; range, 28-91 years), with SSTH treated with PTAE. Thirty-day mortality, technical and clinical success, simplified acute physiology score (SAPS) II, anticoagulation, embolic agent, hematoma volume and location, serum hemoglobin level, hemodynamic instability, and presence of active bleeding at CT and/or angiography were recorded. Clinical success was defined as cessation of bleeding as determined by hemodynamic stability and/or serum hemoglobin level stabilization after PTAE. Univariable and multivariable analyses were performed by using a Cox model to identify variables associated with time to death. Results Mortality rate was 26.8% (30 of 112 patients), angiographic success rate was 95.5% (107 of 112 patients), and clinical success rate was 83% (93 of 112 patients). For surviving patients, mean SAPS II was 19.6 ± 7.1 (range, 13-31) and mean hematoma volume was 862 cm3 ± 618 (range, 238-1887 cm3). For deceased patients, mean SAPS II was 42 ± 13.2 (range, 18-63) and mean hematoma volume was 1419 cm3 ± 788 (range, 251-3492 cm3). SAPS II (P < .001), hematoma volume (P = .01), and retroperitoneal location (P = .01) were independently associated with fatal outcome. Conclusion Percutaneous transarterial embolization is effective for the emergency treatment of spontaneous soft-tissue hematomas. Simplified acute physiology score II, hematoma volume, and retroperitoneal location are predictors of short-term outcome. © RSNA, 2019 Online supplemental material is available for this article.

Transcatheter Arterial Embolization of Spontaneous Soft Tissue Hematomas: A Systematic Review.

BACKGROUND: Severe spontaneous soft tissue hematomas (SSTH) are usually treated with transcatheter arterial embolization (TAE) although only limited retrospective studies exist evaluating this treatment option. The aim of this study was to systematically assess the efficacy and safety of TAE for the management of SSTH. METHODS: Medline, EMBASE, PubMed and Cochrane Library were searched from inception to July 2017 using MeSH headings and a combination of keywords. Eligibility was restricted to original studies with patients suffering from SSTH treated with TAE. Patients with traumatic hematomas or who were treated with solely conservative or surgical management were excluded. For each publication, clinical success based on the control of the bleed, rebleeding rates and complications (including mortality) was collected, as well as technical details. RESULTS: Sixty-three studies met the inclusion criteria, with an aggregate total of 267 patients. Follow-up extended from 1 day to 10 years. Bleeding was mainly localized to the iliopsoas (n = 113/267, 42.3%) and anterior abdominal wall (n = 145/266, 54.7%). When information was available, 81.0% (n = 158/195) of patients were on anticoagulant therapy prior to the bleeding episode. Initial stabilization with control of the bleed was obtained in 93.1% (n = 242 patients, n = 60 studies). The most common embolic materials were coils (n = 129, 54.4%). Rebleeding was reported in 25 patients (9.4%). Only two embolization complications were reported (0.7%). The 30-day mortality was 22.7% (n = 42/1857). CONCLUSION: TAE represents a safe and effective procedure in the management of SSTH. We present a management algorithm based on these data, but further studies are needed to address the knowledge gap.

Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes.

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

Comparative Evaluation of Iodine-125 Radioactive Seed Localization and Wire Localization for Resection of Breast Lesions.

PURPOSE: Radioactive seed localization (RSL) uses a titanium seed labeled with iodine-125 energy for surgery of nonpalpable breast lesions. RSL facilitates radiology-surgery scheduling and allows for improved oncoplasty compared with wire localization (WL). The purpose of this work was to compare the 2 techniques. METHODS: We performed a retrospective study of all breast lesions operated with RSL between February 2013 and March 2015 at our university institution, and compared with an equivalent number of surgeries performed with a single WL. Imaging and pathology reports were reviewed for information on guidance mode, accuracy of targeting, nature of excised lesion, size and volume of surgical specimen, status of margins, and reinterventions. RESULTS: A total of 254 lesions (247 women) were excised with RSL and compared with 257 lesions (244 women) whose surgery was guided by WL. Both groups were comparable in lesion pathology, guidance mode for RSL or WL positioning, and accuracy of targeting (98% correct). Mean delay between biopsy and surgery was 84 days for RSL versus 103 after WL (P = .04). No differences were noted after RSL or WL for surgical specimen mean weight, largest diameter, and volume excised. For malignancies, the rate of positive margins was comparable (2.8%-3%), with 5 of 10 women in the RSL group who underwent a second surgery displaying residual malignancy compared with 3 of 9 women in the WL group. CONCLUSIONS: RSL is safe and accurate, and has comparable surgical endpoints to WL. Because RSL offers flexible scheduling and facilitated oncoplasty, RSL may replace WL for resection of nonpalpable single breast lesions.