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Blood pressure (BP) monitoring and management is essential in the treatment of acute aortic disease (AoD). Previous studies had shown differences between invasive arterial BP monitoring (ABPM) and non-invasive cuff BP monitoring (CBPM), but not whether ABPM would result in patients' change of clinical management. We hypothesized that ABPM would change BP management in AoD patients.This was a prospective observational study of adult patients with AoD admitted to the Critical Care Resuscitation Unit from January 2019 to February 2021. Patients with AoD and both ABPM and CBPM measurements were included. Clinician's BP management goals were assessed in real time before and after arterial catheter placement according to current guidelines. We defined change of management as change of current antihypertensive infusion rate or adding a new agent. We used multivariable logistic and ordinal regressions to determine relevant predictors.We analyzed 117 patients, and 56 (47%) had type A dissection. ABPM was frequently ≥10 mmHg higher than CBPM values. Among 40 (34%) patients with changes in management, 58% (23/40) had [ABPM-CBPM] differences ≥20 mmHg. ABPM prompted increasing current antihypertensive infusion in 68% (27/40) of patients. Peripheral artery disease (OR 13, 95% CI 1.18-50+) was associated with changes in clinical management, and ordinal regression showed hypertension and serum lactate to be associated with differences between ABPM and CBPM.ABPM was frequently higher than CBPM, resulting in 34% of changes of management, most commonly increasing anti-hypertensive infusion rates.

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Introduction: Patients with tIPH (used here to refer to traumatic intraparenchymal hemorrhagic contusion) or intraparenchymal hemorrhage face high rates of mortality and persistent functional deficits. Prior studies have found an association between blood pressure variability (BPV) and neurologic outcomes in patients with spontaneous IPH. Our study investigated the association between BPV and discharge destination (a proxy for functional outcome) in patients with tIPH. Methods: We retrospectively reviewed the charts of patients admitted to a Level I trauma center for ≥ 24 hours with tIPH. We examined variability in hourly BP measurements over the first 24 hours of hospitalization. Our outcome of interest was discharge destination (home vs facility). We performed 1:1 propensity score matching and multivariate regressions to identify demographic and clinical factors predictive of discharge home. Results: We included 354 patients; 91 were discharged home and 263 to a location other than home. The mean age was 56 (SD 21), 260 (73%) were male, 22 (6%) were on anticoagulation, and 54 (15%) on antiplatelet therapy. Our propensity-matched cohorts included 76 patients who were discharged home and 76 who were discharged to a location other than home. One measure of BPV (successive variation in systolic BP) was identified as an independent predictor of discharge location in our propensity-matched cohorts (odds ratio 0.89, 95% confidence interval 0.8-0.98; P = 0.02). Our model demonstrated good goodness of fit (P-value for Hosmer-Lemeshow test = 0.88) and very good discriminatory capability (AUROC = 0.81). High Glasgow Coma Scale score at 24 hours and treatment with fresh frozen plasma were also associated with discharge home. Conclusion: Our study suggests that increased BPV is associated with lower rates of discharge home after initial hospitalization among patients with tIPH. Additional research is needed to evaluate the impact of BP control on patient outcomes.

The calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA is alternatively processed in a tissue-specific manner leading to the production of calcitonin mRNA in thyroid C cells and CGRP mRNA in neurons. A candidate calcitonin/CGRP splice regulator (CSR) isolated from rat brain was shown to inhibit calcitonin-specific splicing in vitro. CSR specifically binds to two regions in the calcitonin-specific exon 4 RNA previously demonstrated to function as a bipartate exonic splice enhancer (ESE). The two regions, A and B element, are necessary for inclusion of exon 4 into calcitonin mRNA. A novel RNA footprinting method based on the UV cross-linking assay was used to define the site of interaction between CSR and B element RNA. Base changes at the CSR binding site prevented CSR binding to B element RNA and CSR was unable to inhibit in vitro splicing of pre-mRNAs containing the mutated CSR binding site. When expressed in cells that normally produce predominantly CGRP mRNA, a calcitonin/CGRP gene containing the mutated CSR binding site expressed predominantly calcitonin mRNA. These observations demonstrate that CSR binding to the calcitonin-specific ESE regulates calcitonin/CGRP pre-mRNA splicing.

The calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA is alternatively processed in a tissue-specific manner leading to the production of calcitonin mRNA in thyroid C cells and CGRP mRNA in neurons. Sequences in the human calcitonin-specific fourth exon function as an exonic splice enhancer (ESE) which is required for incorporation of exon 4 into calcitonin mRNA. Deletion of these sequences from the rat calcitonin/CGRP gene was reported to have no effect on calcitonin splicing. We demonstrate that sequences in the rat calcitonin/CGRP fourth exon act as an ESE. In addition, we observed that three proteins in HeLa nuclear extract, of apparent molecular weights of 40, 55 and 85 kDa, specifically interact with the exon 4 ESE. The 40-kDa protein is human transformer 2β (hTra2β), a homolog of the Drosophila splice regulator transformer 2. hTra2β is required for calcitonin splicing in vitro, one of the first biological functions identified for hTra2β. The 55-kDa protein is SRp55, a member of the SR family of phosphoproteins. Binding of SRp55 to an ESE required for calcitonin mRNA splicing suggests that the different levels of SRp55 present in different cell types may regulate calcitonin/CGRP alternative splicing.