Pre-Test Probability Assessment and d-Dimer Based Evaluation in Patients with Previous Acute Aortic Syndrome.

Background and Objectives. Acute aortic syndromes (AASs) are emergencies burdened by high morbidity and mortality. Guideline-recommended diagnostic workup is based on pre-test probability assessment (PPA) and d-dimer testing. However, the performance of PPA and d-dimer has never been studied in individuals with previous AAS (pAAS), which represent a challenging population. Materials and Methods. We analyzed a registry of patients with pAAS evaluated in two Emergency Departments (EDs) for suspected novel AAS (nAAS). Enrolment criteria were history of pAAS and the presence of truncal pain, syncope or perfusion deficit. All patients underwent advanced imaging. Clinical data were registered prospectively and PPA was performed by applying the aortic dissection detection (ADD) and an aorta simplified (AORTAs) score. Results. A total of 128 patients were enrolled, including 77 patients with previous Stanford type A aortic dissection and 45 patients with previous Stanford type B aortic dissection. The final diagnosis was nAAS in 40 (31%) patients. Clinical variables associated with nAAS were: aortic valve disease, thoracic aortic aneurysm, severe pain, sudden pain, ripping/tearing pain and hypotension/shock. ADD score ≥ 2 had a sensitivity of 65% and a specificity of 83% for nAAS; AORTAs score ≥ 2 had a sensitivity of 48% and a specificity of 88%. d-dimer (cutoff ≥ 500 ng/mL or age-adjusted cutoff) had a sensitivity of 97% and a specificity of 13%/14.7%, for diagnosis of nAAS. Patients that were candidates for guideline-compliant PPA/d-dimer integrated rule-out were: 5 (4.9%) with ADD ≤ 1/d-dimer and 8 (7.8%) with AORTAs ≤ 1/d-dimer < age-adjusted cutoff. None of them had a nAAS. Conclusions. Patients with pAAS evaluated in the ED for red-flag symptoms showed intermediate-to-high pre-test probability of nAAS. The ADD score had lower sensitivity and specificity than in unselected patients. d-dimer, alone and integrated with PPA, was highly sensitive for nAAS, but very unspecific. PPA/d-dimer integrated strategies are unlikely to significantly reduce the number of patients with pAAS undergoing advanced imaging.

Genetic Screening for Potential New Targets in Chronic Myeloid Leukemia Based on Drosophila Transgenic for Human BCR-ABL1.

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome that originates from the reciprocal translocation t(9;22)(q34;q11.2) and encodes for the constitutively active tyrosine kinase protein BCR-ABL1 from the Breakpoint Cluster Region (BCR) sequence and the Abelson (ABL1) gene. Despite BCR-ABL1 being one of the most studied oncogenic proteins, some molecular mechanisms remain enigmatic, and several of the proteins, acting either as positive or negative BCR-ABL1 regulators, are still unknown. The Drosophila melanogaster represents a powerful tool for genetic investigations and a promising model to study the BCR-ABL1 signaling pathway. To identify new components involved in BCR-ABL1 transforming activity, we conducted an extensive genetic screening using different Drosophila mutant strains carrying specific small deletions within the chromosomes 2 and 3 and the gmrGal4,UAS-BCR-ABL1 4M/TM3 transgenic Drosophila as the background. From the screening, we identified several putative candidate genes that may be involved either in sustaining chronic myeloid leukemia (CML) or in its progression. We also identified, for the first time, a tight connection between the BCR-ABL1 protein and Rab family members, and this correlation was also validated in CML patients. In conclusion, our data identified many genes that, by interacting with BCR-ABL1, regulate several important biological pathways and could promote disease onset and progression.