February 2020

Synopsis: Screening asymptomatic patients for cancer is based on the underlying premise that cancers detected before they produce symptoms should be easier to cure than those that are clinically detectable and that earlier treatment could potentially endue the patient with a survival benefit. While mammographic breast cancer screening has proven to be a success story relative to other cancers, women with extremely dense breast tissue complicate the issue with their risk of breast cancer potentially increased and the rate of detection on mammography decreased. Currently, women with extremely dense breast tissue on mammography must be informed of such but it is not clear what further steps, if any, should be taken. This article reports on a randomized clinical trial conducted in the Netherlands where 8061 of 40,373 women (20%) with extremely dense breast tissue who were participating in the national population-based screening program were randomly assigned to be invited for additional MRI screening, 59% of which accepted. Screening was performed every 2 years. In the intention-to-screen population (both those who accepted and refused MRI), the rate of interval cancer detection in the MRI-invitation group was 2.5 per 1000 screenings compared to 5.0 per 1000 screenings in the mammography-only group. The cohort of patients in the MRI-invitation group who refused MRI had a similar rate (4.9 per 1000) of interval cancer detection as the mammography only group.

Of the women who underwent MRI screening, almost 10% were recalled for abnormal scans. Among the 300 women who underwent biopsy on the basis of an MRI indication, 79 were found to have breast cancer for a false positive MRI rate of 74%. Of those cancers found, 72 were stage 0 or I, 70 were node-negative, and 56 were hormone-receptor–positive. The frequency of node-positive cancers was similar among the participants who actually underwent MRI and among those in the mammography-only group (1.9 and 2.2 per 1000 screenings, respectively). For DCIS, the incidence was 15 of 4783 participants (0.31%) among those who underwent MRI and 9 of 32,312 (0.03%) among those in the mammography-only group. 

This study appears to show that among women with dense breasts, the risk of interval cancers is halved by following a negative mammogram with MRI screening. Most of the cancers that were detected on supplemental MRI screening were found at an early stage, however, and it remains unclear whether those tumors would never otherwise have been detected or threatened the patient’s survival. While this trial reinforces the idea that MRI screening is important in women with dense breast tissue, it is still unclear if this contributes to their overall survival.

Synopsis: Early administration of blood products is increasingly utilized in the treatment of trauma and hemorrhagic shock. In 2018, two studies investigated the benefit of prehospital administration of plasma on survival in hemorrhagic shock with seemingly opposing results. The Prehospital Air Medical Plasma (PAMPer) Trial found that early administration of 2 units of thawed plasma was associated with a 30% reduction in mortality for patients in hemorrhagic shock transported by helicopter (PMID: 30044935), while the Control of Major Bleeding After Trauma (COMBAT) Trial did not find an association between prehospital plasma and survival in patients transported by ground (PMID: 30032977). In this follow up in JAMA Surgery. the PAMPer and COMBAT teams reconcile these differences by using post hoc analysis of patients from both trials to find that prehospital plasma administration was associated with improved survival when transport times were greater than 20 minutes irrespective of mode of transportation. One interesting aspect of this work was that the PAMPer and COMBAT Trials were harmonized in advance i.e. great care was taken at the outset of protocol development to ensure that the groups, inclusion/exclusion criteria, time points, blood collection, and other aspects of data collection used in both trials were standardized as much as possible. In addition, they also aligned with the Trans-Agency Consortium for Trauma-Induced Coagulopathy (TACTIC) Project (PMID: 26307885). This collaboration enables future translational studies to potentially use the samples collected in the PAMPer and COMBAT Trials to better understand the mechanisms underlying the time-dependent impact of plasma on survival in hemorrhagic shock and other observations. 

Synopsis: Carotid endartectomy (CEA) and transfemoral carotid stenting (TF-CAS) have been well established treatment modalities for carotid artery disease with excellent results to-date. Still, there remains a subset of patients who may not be ideal candidates for TF-CAS because of poor access anatomy or severe aortic arch disease, and who also have contraindications for CEA. TransCarotid artery revascularization (TCAR) is a new technology that allows for endovascular repair of carotid artery disease that avoids catheter access from the groin through the aortic arch via a small incision above the clavicle to directly access the common carotid artery, while still maintaining cerebral protection through an extracorporeal arteriovenous shunt from the carotid artery to the femoral vein prior to manipulating the target lesion.

The Vascular Quality Initiative (VQI) TCAR Surveillance Project and Transfemoral Carotid Stent Registry (2016-2019) was queried to evaluate short- and long-term outcomes for 5,251 TCAR patients and 6,640 TF-CAS patients. From this sample, 3,286 pairs of patients were analyzed using propensity score matching. While patients undergoing TCAR were older and had more coexisting medical conditions than those undergoing TF-CAS overall, the two cohorts generated for subsequent analysis were well-matched. Overall, TCAR was associated with lower rates of in-hospital stroke or death (1.6% TCAR vs. 3.1% TF-CAS, p<0.001)as well as the individual rates of stroke (1.3% vs. 2.4%, p=0.001) and death (0.4% vs. 1.0%, p=0.008). Although there were no statistically significant differences in overall access site bleeding complications (3.5% vs 3.8%; p=0.55), TCAR was associated with a higher risk of access site bleeding resulting in interventional treatment (1.3% vs 0.8%, p = .04). There were no differences between TCAR and TF-CAS for in-hospital myocardial infarction (0.2% vs. 0.3%, p=0.47). Total fluoroscopy time (5 mins vs. 16 mins, p<.001), total contrast volume (30 mL vs. 80 mL, p<.001), and embolic protection placement failure (0.3% vs. 5.8%, p<0.001) all favored the TCAR group. In patients with 1 year follow up (46% TCAR patients vs. 54% TF-CAS patients), ipsilateral stroke or death was lower in the TCAR group (5.1% vs. 9.6%, p<.001). 

Upon further analysis, the significant difference in in-hospital stroke and death rates between TCAR and TF-CAS appeared to be driven primarily by presenting symptom status (i.e., symptomatic vs. asymptomatic). When the patient cohorts were partitioned according to their symptomatic status, the rates of stroke, death, and stroke or death were no different between asymptomatic patients undergoing TCAR or TF-CAS (0.7% vs. 1.3% stroke, p=0.13; 0.4% vs. 0.2% death, p=0.32; 1.0% vs. 1.5% stroke or death, p=0.32.). However, significant differences in these same outcomes remained for symptomatic patients undergoing TCAR vs. TF-CAS, with the results continuing to favor TCAR (2.0% vs. 3.1% stroke, p=0.04; 0.5% vs. 1.5% death, p=0.002; 2.1% vs. 4.2% stroke or death, p<0.001). 

There are some limitations worth noting. TCAR is a new technology and patients are highly scrutinized and selected for intervention. Real world registries lack randomization of treatment options, which are instead selected by the treating physician. Thus, despite matching, unmeasured confounders may be present which impact the analysis of outcomes. Additionally, there is limited detail on patient anatomy in the datasets. Location and characteristics of carotid disease, severity of arch disease, and type and anatomic distribution of strokes are all relevant to outcomes, but not provided in this analysis.