Citations

AbstractCopy number variation (CNV) is a common form of structural variation detected in human genomes, occurring as both constitutional and somatic events. Cytogenetic techniques like chromosomal microarray (CMA) are widely used in analyzing CNVs. However, CMA techniques cannot resolve the full nature of these structural variations (i.e. the orientation and location of associated breakpoint junctions) and must be combined with other cytogenetic techniques, such as karyotyping or FISH, to do so. This makes the development of a next‐generation sequencing (NGS) approach capable of resolving both CNVs and breakpoint junctions desirable. Mate‐pair sequencing (MPseq) is a NGS technology designed to find large structural rearrangements across the entire genome. Here we present an algorithm capable of performing copy number analysis from mate‐pair sequencing data. The algorithm uses a step‐wise procedure involving normalization, segmentation, and classification of the sequencing data. The segmentation technique combines both read depth and discordant mate‐pair reads to increase the sensitivity and resolution of CNV calls. The method is particularly suited to MPseq, which is designed to detect breakpoint junctions at high resolution. This allows for the classification step to accurately calculate copy number levels at the relatively low read depth of MPseq. Here we compare results for a series of hematological cancer samples that were tested with CMA and MPseq. We demonstrate comparable sensitivity to the state‐of‐the‐art CMA technology, with the benefit of improved breakpoint resolution. The algorithm provides a powerful analytical tool for the analysis of MPseq results in cancer.

Objective(1) Assess 3‐dimensional volumetric growth of untreated sporadic vestibular schwannomas (VSs) in a large cohort of patients treated with conservative observation. (2) Compare volumetric and conventional linear diameter measurements for detecting tumor growth.Study DesignCase series with chart review.SettingTertiary skull base referral center.Subjects and MethodsPatients with sporadic VS who elected initial conservative treatment with at least 2 serial magnetic resonance imaging (MRI) scans were included. Tumor volume was determined with 3‐dimensional segmentation of MRI sequences. The volumetric threshold for tumor growth was an increase ≥20% from baseline tumor volume. Tumor size based on linear diameter was assessed with the 1995 American Academy of Otolaryngology—Head and Neck Surgery Foundation guidelines for VS outcome reporting, with growth defined as an increase ≥2 mm.ResultsA total of 361 patients were included with a median radiologic follow‐up of 4.1 years (interquartile range [IQR], 2.5‐6.8). At diagnosis, 232 VSs (64%) were purely intracanalicular, and 129 (36%) extended into the cerebellopontine angle. The median baseline tumor volume was 0.161 cm3 (IQR, 0.054‐0.418). Overall, 69% of tumors demonstrated volumetric growth at a median of 1.1 years (IQR, 0.6‐2.1) after initial MRI. In contrast, based on linear measurement assessment, 48% of tumors demonstrated growth at a median of 1.8 years (IQR, 0.8‐3.1) from first MRI scan. Disequilibrium, facial hypoesthesia, aural fullness, initial tumor size, and nonincidental diagnosis were associated with tumor growth.ConclusionThree‐dimensional volumetric assessment of VS provides a more sensitive measure of tumor growth when compared with linear diameter assessment. Through volumetric analysis, the current study revealed that a significant proportion of VSs demonstrate growth during observation.

Objectives: Midodrine is an oral alpha-agonist approved for orthostatic hypotension. The use of midodrine as a vasopressor sparing agent has steadily increased in the ICU despite limited evidence for its safety in that setting. We describe the trends in use and reported side effects and complications of midodrine in multidisciplinary ICUs of a tertiary care institution. Design: Single-center retrospective case series. Setting: Medical and surgical ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. Patients: Adult patients admitted to any ICU who received midodrine for hypotension were eligible. Interventions: None. Measurements and Main Results: We reviewed the mean arterial pressures and cumulative vasopressor dose before and after midodrine administration and assessed for reported complications. During the study period, a total of 1,119 patients were initiated on midodrine, 56% in surgical ICUs, 42% in medical ICUs, and 2% in a mixed medical and surgical neurology ICU. There was a significant decrease in the number of patients on vasopressors 24 hours after initiation of midodrine (663 to 344; p < 0.001); among the patients that remained on vasopressors, there was a significant decrease in the median cumulative vasopressor dose (p = 0.002). There was a significant increase in median mean arterial pressure 24 hours after initiation of midodrine among patients who were not on vasopressors (65–68; p < 0.01). Asymptomatic bradycardia (heart rate < 50 beats/min) was the most common side effect (n = 172 patients, median 39 beats/min). Two patients developed bowel ischemia after initiation of midodrine that prompted discontinuation of midodrine in one case. Evaluating trends of utilization, the off-label use of midodrine has increased steadily over the years across ICUs. Conclusions: Our results suggest that midodrine is being increasingly used as an adjunct to increase mean arterial pressure and facilitate weaning of vasopressors in the ICU. Prospective trials are required to further establish the appropriate timing, efficacy, safety, and cost-effectiveness of midodrine use in ICU patients.

Background and Purpose: Management of carotid stenosis remains controversial despite several trials evaluating carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS). We compared attitudes in the management of carotid stenosis between selected experts within Europe and North America. Methods: A 3-phase Delphi survey was e-mailed to select stroke experts from Europe (n = 390) and North America (n = 289). Those completing the initial survey were shown all responses after each survey round. Consensus was defined as ≥80% agreement. Results: For phases 1, 2, and 3, response rates were 32%, 62%, and 73%, respectively. Overall, 100 (15%) of 679 participated in all 3 phases, 19% Europeans versus 9% North Americans ( P = .0007). The European group reached consensus in 6 of 15 statements; The North American group reached consensus in 4 of 15. Ninety percentage of Europeans versus 70% of North Americans ( P = .017) stated CEA is superior to CAS for symptomatic carotid stenosis. This difference was not significant in the final model (adjusted odds ratio: 3.72 [95% confidence interval: 0.95-14.5]). Sixty-nine percentage of North Americans agreed there is a stronger indication for CAS over CEA in patients younger than 65 years for symptomatic carotid stenosis, whereas 55% of Europeans ( P = .023) disagreed. For asymptomatic carotid stenosis, when asked how likely they would recommend CAS, 62% North Americans said “sometimes” versus 60% of Europeans said “never” ( P = .06). Conclusion: The majority of North American and European respondents did not consider the 2 procedures equivalent and seemed to indicate that CEA was preferred for the management of carotid stenosis. These findings need to be further explored to help establish evidence-based guidelines.