The authors report the 6-year results of the Barrow Ruptured Aneurysm Trial (BRAT). This ongoing randomized trial, with the final goal of a 10-year follow-up, compares the safety and efficacy of ...surgical clip occlusion and endovascular coil embolization in patients presenting with subarachnoid hemorrhage (SAH) from a ruptured aneurysm. The 1- and 3-year results of this trial have been previously reported.
In total, 500 patients with an SAH met the entry criteria and were enrolled in the study. Of these patients, 471 were randomly assigned to the treatments: 238 to surgical clipping and 233 to endovascular coiling. Six patients who died before treatment and 57 patients with nonaneurysmal SAHs were excluded, leaving a total of 408 patients who underwent clipping (209 assigned) or coiling (199 assigned). Whether to treat patients within the assigned group or to cross over patients to the other group was at the discretion of the treating physician; 38% (75/199) of the patients assigned to coiling were crossed over to clipping and 1.9% (4/209) assigned to clipping were crossed over to coiling. The outcome data were collected by a dedicated nurse practitioner. The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. Six years after randomization, 336 (82%) of 408 patients who had been treated were available for examination.
On the basis of an mRS score of > 2, and similar to the results at the 3-year follow-up, no significant difference in outcomes (p = 0.24) was detected between the 2 treatment groups. Complete aneurysm obliteration at 6 years was achieved in 96% (111/116) of the clipping group and in 48% (23/48) of the coiling group (p < 0.0001). In the period between the 3- and 6-year follow-ups, 3 additional patients assigned to coiling and none assigned to clipping received retreatment, for overall retreatment rates of 4.6% (13/280) for clipping and 16.4% (21/128) for coiling (p < 0.0001). When aneurysm location was considered, the 6-year results continued to match the previously reported results, with no difference in outcome for anterior circulation aneurysms at most time points. Of the anterior circulation aneurysms assigned to coiling treatment, 42% (70/168) were crossed over to clipping treatment. The outcomes for posterior circulation aneurysms continued to favor coiling. The randomization process was unexpectedly skewed, with 18 of 21 treated aneurysms of the posterior inferior cerebellar artery (PICA) being assigned to clipping, but even when PICA aneurysms were removed from the analysis, outcomes for the posterior circulation aneurysms still favored coiling.
Although BRAT was statistically underpowered to detect small differences, these results suggest little difference in outcome between the 2 treatments for anterior circulation aneurysms. This was not the case for the posterior circulation aneurysms, where coil embolization appeared to provide a sustained advantage over clipping. Aneurysm obliteration rates in BRAT were significantly lower and retreatment rates significantly higher in the patients undergoing coiling than in those undergoing clipping. However, despite the fact that retreatment rates were higher after coiling, no recurrent hemorrhages were known to have occurred in patients undergoing coiling in BRAT who were followed up for 6 years. Sufficient questions remain about the relative benefits of the 2 treatment modalities to warrant further well-designed randomized trials.
Increased nutrient loading into estuaries causes the accumulation of algal biomass, and microbial degradation of this organic matter decreases oxygen levels and contributes towards hypoxia. A second, ...often overlooked consequence of microbial degradation of organic matter is the production of carbon dioxide (CO2) and a lowering of seawater pH. To assess the potential for acidification in eutrophic estuaries, the levels of dissolved oxygen (DO), pH, the partial pressure of carbon dioxide (pCO2), and the saturation state for aragonite (Ωaragonite) were horizontally and vertically assessed during the onset, peak, and demise of low oxygen conditions in systems across the northeast US including Narragansett Bay (RI), Long Island Sound (CT–NY), Jamaica Bay (NY), and Hempstead Bay (NY). Low pH conditions (<7.4) were detected in all systems during summer and fall months concurrent with the decline in DO concentrations. While hypoxic waters and/or regions in close proximity to sewage discharge had extremely high levels of pCO2, (>3000 μatm), were acidic pH (<7.0), and were undersaturated with regard to aragonite (Ωaragonite < 1), even near-normoxic but eutrophic regions of these estuaries were often relatively acidified (pH < 7.7) during late summer and/or early fall. The close spatial and temporal correspondence between DO and pH and the occurrence of extremes in these conditions in regions with the most intense nutrient loading indicated that they were primarily driven by microbial respiration. Given that coastal acidification is promoted by nutrient-enhanced organic matter loading and reaches levels that have previously been shown to negatively impact the growth and survival of marine organisms, it may be considered an additional symptom of eutrophication that warrants managerial attention.
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•Low pH detected in NE US estuaries during summer and fall concurrent with low DO concentrations.•All systems had regions with high pCO2 (>1000 μatm), low pH (<7.5) and Ωaragonite < 1.•Eutrophication enhanced microbial respiration was the prime source of acidification.•Acidification reached levels shown to negatively affect marine life in prior studies.
A key challenge in climate science is to separate observed temperature changes into components due to internal variability and responses to external forcing. Extended integrations of forced and ...unforced climate models are often used for this purpose. Here we demonstrate a novel method to separate modes of internal variability from global warming based on differences in time scale and spatial pattern, without relying on climate models. We identify uncorrelated components of Pacific sea surface temperature variability due to global warming, the Pacific Decadal Oscillation (PDO), and the El Niño–Southern Oscillation (ENSO). Our results give statistical representations of PDO and ENSO that are consistent with their being separate processes, operating on different time scales, but are otherwise consistent with canonical definitions. We isolate the multidecadal variability of the PDO and find that it is confined to midlatitudes; tropical sea surface temperatures and their teleconnections mix in higher‐frequency variability. This implies that midlatitude PDO anomalies are more persistent than previously thought.
Key Points
A novel method is presented to separate internal variability from global warming based on differences in time scale and spatial pattern
The key features of the Pacific Decadal Oscillation and El Niño‐Southern Oscillation are consistent with their being separate processes
Decadal variability associated with the Pacific Decadal Oscillation is confined to the midlatitude North Pacific
OBJECTIVE The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial in which treatment with clipping was compared to treatment with coil embolization. Patients were randomized to ...treatment on presentation with any nontraumatic subarachnoid hemorrhage (SAH). Because all other randomized trials comparing these 2 types of treatments have been limited to saccular aneurysms, the authors analyzed the current BRAT data for this subgroup of lesions. METHODS The primary BRAT analysis included all sources of SAH: nonaneurysmal lesions; saccular, blister, fusiform, and dissecting aneurysms; and SAHs from an aneurysm associated with either an arteriovenous malformation or a fistula. In this post hoc review, the outcomes for the subgroup of patients with saccular aneurysms were further analyzed by type of treatment. The extent of aneurysm obliteration was adjudicated by an independent neuroradiologist not involved in treatment. RESULTS Of the 471 patients enrolled in the BRAT, 362 (77%) had an SAH from a saccular aneurysm. Patients with saccular aneurysms were assigned equally to the clipping and the coiling cohorts (181 each). In each cohort, 3 patients died before treatment and 178 were treated. Of the 178 clip-assigned patients with saccular aneurysms, 1 (1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. There was no statistically significant difference in poor outcome (modified Rankin Scale score > 2) between these 2 treatment arms at any recorded time point during 6 years of follow-up. After the initial hospitalization, 1 of 241 (0.4%) clipped saccular aneurysms and 21 of 115 (18%) coiled saccular aneurysms required retreatment (p < 0.001). At the 6-year follow-up, 95% (95/100) of the clipped aneurysms were completely obliterated, compared with 40% (16/40) of the coiled aneurysms (p < 0.001). There was no difference in morbidity between the 2 treatment groups (p = 0.10). CONCLUSIONS In the subgroup of patients with saccular aneurysms enrolled in the BRAT, there was no significant difference between modified Rankin Scale outcomes at any follow-up time in patients with saccular aneurysms assigned to clipping compared with those assigned to coiling (intent-to-treat analysis). At the 6-year follow-up evaluation, rates of retreatment and complete aneurysm obliteration significantly favored patients who underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).
Objective
Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been ...reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS.
Methods
A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face‐to‐face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada.
Results
Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS.
Conclusion
Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence‐based guidelines for the treatment of juvenile LS.
Digital flat-panel detector cone-beam computed tomography (CBCT) has recently been adapted for use with C-arm systems. This configuration provides projection radiography, fluoroscopy, digital ...subtraction angiography, and volumetric computed tomography (CT) capabilities in a single patient setup, within the interventional suite. Such capabilities allow the interventionalist to perform intraprocedural volumetric imaging without the need for patient transportation. Proper use of this new technology requires an understanding of both its capabilities and limitations. This article provides an overview of C-arm CBCT with particular attention to trade-offs between C-arm CBCT systems and conventional multi-detector CT.
The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 ...virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses HKU1, OC43, NL63, and 229E; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus RSV RSV subtype A and RSV subtype B) and 2 bacteria (
and
) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (
= 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval CI, 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive "sample-to-answer" multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.
C-arm cone-beam computed tomography (CT) with a flat-panel detector represents the next generation of imaging technology available in the interventional radiology suite and is predicted to be the ...platform for many of the three-dimensional (3D) roadmapping and navigational tools that will emerge in parallel with its integration. The combination of current and unappreciated capabilities may be the foundation on which improvements in both safety and effectiveness of complex vascular and nonvascular interventional procedures become possible. These improvements include multiplanar soft tissue imaging, enhanced pretreatment target lesion roadmapping and guidance, and the ability for immediate multiplanar posttreatment assessment. These key features alone may translate to a reduction in the use of iodinated contrast media, a decrease in the radiation dose to the patient and operator, and an increase in the therapeutic index (increase in the safety-vs-benefit ratio). In routine practice, imaging information obtained with C-arm cone-beam CT provides a subjective level of confidence factor to the operator that has not yet been thoroughly quantified.
The invertebrate cytolysin lysenin is a member of the aerolysin family of pore-forming toxins that includes many representatives from pathogenic bacteria. Here we report the crystal structure of the ...lysenin pore and provide insights into its assembly mechanism. The lysenin pore is assembled from nine monomers via dramatic reorganization of almost half of the monomeric subunit structure leading to a β-barrel pore ∼10 nm long and 1.6-2.5 nm wide. The lysenin pore is devoid of additional luminal compartments as commonly found in other toxin pores. Mutagenic analysis and atomic force microscopy imaging, together with these structural insights, suggest a mechanism for pore assembly for lysenin. These insights are relevant to the understanding of pore formation by other aerolysin-like pore-forming toxins, which often represent crucial virulence factors in bacteria.
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