Melanoma is an extremely aggressive cancer for which the American Academy of Dermatology currently does not have formal recommendations outlining a timeline from biopsy to definitive treatment. Our dermatology department investigated our treatment timeline for melanoma. Using the database from our electronic medical record, Epic, we evaluated patients over a one-year period; in total we identified 109 melanomas. We evaluated patient demographics, tumor characteristics, and timelines regarding diagnosis and treatments. There was a statistically significant difference in patient notification of diagnosis and treatment times between stage 1 and stages 2-4 combined (based on the American Joint Committee on Cancer staging system). We found that 84% of melanomas were treated within 4 weeks of diagnosis and 96% within 6 weeks. The lower the stage, the earlier the melanoma was definitively treated; higher stage melanomas had a longer delay to definitive treatment. Herein, we have presented our single institutional experience of the melanoma timeline from diagnosis to definitive treatment and have identified factors that impact timely definitive treatment.

Background and purpose

Nearly 20% of patients with spontaneous SAH have no definitive source on initial DSA. The purpose of this study was to investigate the timing and yield of repeat DSA, to clarify the influence of initial CT bleed pattern, and to characterize sources of diagnostic error in this scenario.

Materials and methods

We evaluated the yield of repeat DSA and clinical outcomes stratified by hemorrhage pattern on CT in consecutive patients with nontraumatic SAH with negative initial DSA findings at a referral center. Cases in which the culprit lesion was subsequently diagnosed were classified as physiologically occult (ie, undetectable) on the initial DSA, despite adequate technique and interpretation or misdiagnosed due to operator-dependent error.

Results

Two hundred forty-two of 1163 (20.8%) patients with spontaneous SAH had negative initial DSA findings between 2009 and 2018. The SAH CT pattern was nonperimesencephalic (41%), perimesencephalic (36%), sulcal (18%), and CT-negative (5%). Repeat DSA in 135/242 patients (55.8%) revealed a source in 10 patients (7.4%): 4 saccular aneurysms, 4 atypical aneurysms, and 2 arteriovenous shunts. The overall yield of repeat DSA was 11.3% with nonperimesencephalic and 2.2% for perimesencephalic patterns. The yield of the second and third DSAs with a nonperimesencephalic pattern was 7.7% and 12%, respectively. Physiologically occult lesions accounted for 6/242 (2.5%) and operator-dependent errors accounted for 7/242 (2.9%) of all angiographically occult lesions on the first DSA.

Conclusions

Atypical aneurysms and small arteriovenous shunts are important causes of SAH negative on angiography. Improving DSAs technique can modestly reduce the need for repeat DSA; however, a small fraction of SAH sources remain occult despite adequate technique. These findings support the practice of repeating DSA in patients with a nonperimesencephalic SAH pattern.

Background

Flatfish cranial asymmetry represents one of the most remarkable morphological innovations among vertebrates, and has fueled vigorous debate on the manner and rate at which strikingly divergent phenotypes evolve. A surprising result of many recent molecular phylogenetic studies is the lack of support for flatfish monophyly, where increasingly larger DNA datasets of up to 23 loci have either yielded a weakly supported flatfish clade or indicated the group is polyphyletic. Lack of resolution for flatfish relationships has been attributed to analytical limitations for dealing with processes such as nucleotide non-stationarity and incomplete lineage sorting (ILS). We tackle this phylogenetic problem using a sequence dataset comprising more than 1,000 ultraconserved DNA element (UCE) loci covering 45 carangimorphs, the broader clade containing flatfishes and several other specialized lineages such as remoras, billfishes, and archerfishes.

Results

We present a phylogeny based on UCE loci that unequivocally supports flatfish monophyly and a single origin of asymmetry. We document similar levels of discordance among UCE loci as in previous, smaller molecular datasets. However, relationships among flatfishes and carangimorphs recovered from multilocus concatenated and species tree analyses of our data are robust to the analytical framework applied and size of data matrix used. By integrating the UCE data with a rich fossil record, we find that the most distinctive carangimorph bodyplans arose rapidly during the Paleogene (66.0-23.03 Ma). Flatfish asymmetry, for example, likely evolved over an interval of no more than 2.97 million years.

Conclusions

The longstanding uncertainty in phylogenetic hypotheses for flatfishes and their carangimorph relatives highlights the limitations of smaller molecular datasets when applied to successive, rapid divergences. Here, we recovered significant support for flatfish monophyly and relationships among carangimorphs through analysis of over 1,000 UCE loci. The resulting time-calibrated phylogeny points to phenotypic divergence early within carangimorph history that broadly matches with the predictions of adaptive models of lineage diversification.

Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para-cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically congested products and reaction of highly substituted alkenes and allenes. In addition, the mechanistic details of the process are studied, which revealed a reversible radical addition and a selectivity-determining radical recombination. The regio- and stereochemical outcome of the reaction is also rationalized.

Background and purpose

Case reports demonstrate that coiling of a sigmoid sinus diverticulum can treat pulsatile tinnitus. We hypothesized that MR imaging 4D flow and computational fluid dynamics would reveal distinct blood flow patterns in the venous outflow tract in these patients.

Materials and methods

Patients with pulsatile tinnitus of suspected venous etiology underwent MR imaging at 3T, using venous phase contrast-enhanced MR angiography, 4D flow, and 2D phase contrast. The contrast-enhanced MRA contours were evaluated to determine the presence and extent of a sigmoid sinus diverticulum. Computational fluid dynamics analysis was performed using the 4D flow inlet flow and the luminal contours from contrast-enhanced MRA as boundary conditions. In addition, computational fluid dynamics was performed for the expected post treatment conditions by smoothing the venous geometry to exclude the sigmoid sinus diverticulum from the anatomic boundary conditions. Streamlines were generated from the 4D flow and computational fluid dynamics velocity maps, and flow patterns were examined for the presence of rotational components.

Results

Twenty-five patients with pulsatile tinnitus of suspected venous etiology and 10 control subjects were enrolled. Five (20%) of the symptomatic subjects had sigmoid sinus diverticula, all associated with an upstream stenosis. In each of these patients, but none of the controls, a stenosis-related flow jet was directed toward the opening of the sigmoid sinus diverticulum with rotational flow patterns in the sigmoid sinus diverticulum and parent sigmoid sinus on both 4D flow and computational fluid dynamics.

Conclusions

Consistent patterns of blood flow can be visualized in a sigmoid sinus diverticulum and the parent sinus using 4D flow and computational fluid dynamics. Strong components of rotational blood flow were seen in subjects with sigmoid sinus diverticula that were absent in controls.