Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Successful integration of thyroid cytopathology and surgical pathology education in an E-module format

Context: The shift to digital learning in medicine is well underway and in fact spurred by the COVID-19 pandemic. The didactic portion of our institution's cytotechnology (CT) education program is online and delivered to learners across the nation. With CT education elevating to the master’s degree level, there is a need to expand cytologic correlation with surgical resection specimens. We also wanted to afford pathology residents the same. Methods: We developed an online cytologic–histologic correlation digital learning module (e-module) addressing thyroid fine needle aspirations (FNAs) and surgical thyroidectomy specimens which was administered as part of coursework in the CT education and pathology residency programs. The module was 35 min long and consisted of guided narration with both formative and summative interactive quizzes. After completion of the module, participants were invited to fill a brief survey comprised of multiple choice, Likert, and free response questions. This study was approved by the institutional review board. Results: The 29 respondents were comprised of 22 CT students and 7 residents. CT students had minimal experience thyroid pathology prior to the module; residents were mixed. Twenty-three (79.3%) ranked the highest tiers for learning cytopathology through this module, 24 (82.8%) for learning thyroid surgical pathology, and 25 (86.2%) for cytologic–histologic correlation. All respondents stated they would like similar activities in the future. Conclusions: Teaching cytology–histology correlation for thyroid in an electronic format was effective and well-received by participants. There is a demand for these activities among current learners, suggesting that expanding the available repertoire will be beneficial

Peak wall stress predicts expansion rate in descending thoracic aortic aneurysms.

BACKGROUND: Aortic diseases, including aortic aneurysms, are the 12th leading cause of death in the United States. The incidence of descending thoracic aortic aneurysms is estimated at 10.4 per 100,000 patient-years. Growing evidence suggests that stress measurements derived from structural analysis of aortic geometries predict clinical outcomes better than diameter alone. METHODS: Twenty-five patients undergoing clinical and radiologic surveillance for thoracic aortic aneurysms were retrospectively identified. Custom MATLAB algorithms were employed to extract aortic wall and intraluminal thrombus geometry from computed tomography angiography scans. The resulting reconstructions were loaded with 120 mm Hg of pressure using finite element analysis. Relationships among peak wall stress, aneurysm growth, and clinical outcome were examined. RESULTS: The average patient age was 71.6 ± 10.0 years, and average follow-up time was 17.5 ± 9 months (range, 6 to 43). The mean initial aneurysm diameter was 47.8 ± 8.0 mm, and the final diameter was 52.1 ± 10.0 mm. Mean aneurysm growth rate was 2.9 ± 2.4 mm per year. A stronger correlation (r = 0.894) was found between peak wall stress and aneurysm growth rate than between maximal aortic diameter and growth rate (r = 0.531). Aneurysms undergoing surgical intervention had higher peak wall stresses than aneurysms undergoing continued surveillance (300 ± 75 kPa versus 229 ± 47 kPa, p = 0.01). CONCLUSIONS: Computational peak wall stress in thoracic aortic aneurysms was found to be strongly correlated with aneurysm expansion rate. Aneurysms requiring surgical intervention had significantly higher peak wall stresses. Peak wall stress may better predict clinical outcome than maximal aneurysmal diameter, and therefore may guide clinical decision-making

Peak wall stress predicts expansion rate in descending thoracic aortic aneurysms.

BACKGROUND: Aortic diseases, including aortic aneurysms, are the 12th leading cause of death in the United States. The incidence of descending thoracic aortic aneurysms is estimated at 10.4 per 100,000 patient-years. Growing evidence suggests that stress measurements derived from structural analysis of aortic geometries predict clinical outcomes better than diameter alone. METHODS: Twenty-five patients undergoing clinical and radiologic surveillance for thoracic aortic aneurysms were retrospectively identified. Custom MATLAB algorithms were employed to extract aortic wall and intraluminal thrombus geometry from computed tomography angiography scans. The resulting reconstructions were loaded with 120 mm Hg of pressure using finite element analysis. Relationships among peak wall stress, aneurysm growth, and clinical outcome were examined. RESULTS: The average patient age was 71.6 ± 10.0 years, and average follow-up time was 17.5 ± 9 months (range, 6 to 43). The mean initial aneurysm diameter was 47.8 ± 8.0 mm, and the final diameter was 52.1 ± 10.0 mm. Mean aneurysm growth rate was 2.9 ± 2.4 mm per year. A stronger correlation (r = 0.894) was found between peak wall stress and aneurysm growth rate than between maximal aortic diameter and growth rate (r = 0.531). Aneurysms undergoing surgical intervention had higher peak wall stresses than aneurysms undergoing continued surveillance (300 ± 75 kPa versus 229 ± 47 kPa, p = 0.01). CONCLUSIONS: Computational peak wall stress in thoracic aortic aneurysms was found to be strongly correlated with aneurysm expansion rate. Aneurysms requiring surgical intervention had significantly higher peak wall stresses. Peak wall stress may better predict clinical outcome than maximal aneurysmal diameter, and therefore may guide clinical decision-making

Generic Revision of the Holocystitidae of North America (Diploporita, Echinodermata) Based on Universal Elemental Homology

The Holocystites Fauna is an enigmatic group of North American diploporitans that presents a rare window into unusual middle Silurian echinoderm communities. Multiple systematic revisions have subdivided holocystitids on the basis of presumed differences in oral area plating and respiratory structures. However, these differences were based on a fundamental misunderstanding of the homologous elements of the oral area and the taphonomic process; taphonomic disarticulation of the oral area formed the basis for the erection of Pentacystis and Osgoodicystis as separate genera, and Osgoodicystis is interpreted as the junior synonym of Pentacystis. Holocystitids show a conservative peristomial bordering plate pattern that is shared among all described genera. The peristome is bordered by seven interradially positioned oral plates as is typical for oral plate–bearing blastozoans. A second open circlet of facetal plates lies distal to the oral plates; five of these facetal plates bear facets for feeding appendages (lost on the A ambulacrum in some taxa), while two lateral facets (present in all taxa except Pustulocystis) do not. Holocystitid taxa show minor modifications to this basic peristomial bordering plate pattern. As thecal morphologies are highly variable within populations, taxonomic revision of holocystitids is based on modifications of the plating of the oral area