Soft Polyethylene Glycol Hydrogels Support Human PSC Pluripotency and Morphogenesis.

Lumenogenesis within the epiblast represents a critical step in early human development, priming the embryo for future specification and patterning events. However, little is known about the specific mechanisms that drive this process due to the inability to study the early embryo in vivo. While human pluripotent stem cell (hPSC)-based models recapitulate many aspects of the human epiblast, most approaches for generating these 3D structures rely on ill-defined, reconstituted basement membrane matrices. Here, we designed synthetic, nonadhesive polyethylene glycol (PEG) hydrogel matrices to better understand the role of matrix mechanical cues in iPSC morphogenesis, specifically elastic modulus. First, we identified a narrow range of hydrogel moduli that were conducive to the hPSC viability, pluripotency, and differentiation. We then used this platform to investigate the effects of the hydrogel modulus on lumenogenesis, finding that matrices of intermediate stiffness yielded the most epiblast-like aggregates. Conversely, stiffer matrices impeded lumen formation and apico-basal polarization, while the softest matrices yielded polarized but aberrant structures. Our approach offers a simple, modular platform for modeling the human epiblast and investigating the role of matrix cues in its morphogenesis.

Invasive Strategies for the Treatment of Pulmonary Embolism. Where Are We in 2020?

Pulmonary Embolism (PE) is the third most common cause of cardiovascular mortality in the United States, with 60,000-100,000 deaths per year following myocardial infarction and stroke. During the past 5 years, there has been an introduction of novel interventions as a result of a renewed interest in optimizing PE management, particularly among those individuals with more severe disease of hemodynamic significance. The cornerstone treatment for PE is anticoagulation. More aggressive alternatives have been considered for patients with intermediate and high-risk PE. In general, these options can be grouped into 3 different categories: systemic thrombolysis, catheter-directed interventions, and surgical embolectomy. Systemic thrombolysis has shown statistical benefit in several randomized trials for intermediate- and high-risk PE, however, this benefit has been offset by an elevated risk of major bleeding and intracerebral hemorrhage, limiting their use in clinical practice. Catheter-directed thrombolysis refers to catheter-directed injection of a thrombolytic drug directly into the pulmonary artery. Three interventional devices (EKOSonic endovascular system, FlowTriever embolectomy device and the Indigo thrombectomy system) have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. As of today, catheter-based interventions are limited to small randomized trials and single arm-prospective studies focused on short-term surrogate endpoints. Although single arm studies carry some value establishing the preliminary safety and effectiveness of these devices, they are not sufficient to stratify risk and guide clinical practice. Furthermore, no trials have been performed with enough power to assess potential mortality benefit with the use of catheter-directed thrombolysis or catheter-based embolectomy devices, hence treatment decisions continue to be influenced by individual risk of bleeding, the location of thrombus and operator expertise until additional evidence becomes available.

The Face Is the Mirror of the Soul. The Cardiovascular Physical Exam Is Not Yet Dead!

Cardiac pathology can be congenital or acquired with underlying genetic predispositions. In this era of medicine there is a concern that the comprehensive physical examination doctors prided themselves on is becoming a lost art. Research studies have also revealed a decline in physical examination skills. The full clinical cardiovascular examination is indeed quite complex and does take significant time to master. It is critical that physicians be competent in the physical exam. Not identifying subtle clinical findings leading to missed or delayed diagnosis which can lead to significant morbidity and mortality. In this paper we intend to highlight the clinical cardiovascular findings that may be detected on patients even before initiating the physical exam. The head and neck visual examination may be quite revealing.

Can Computed Fractional Flow Reserve Coronary CT Angiography (FFRCT) Offer an Accurate Noninvasive Comparison to Invasive Coronary Angiography (ICA)? "The Noninvasive CATH." A Comprehensive Review.

Invasive coronary angiography (ICA) serves as a very important tool in the diagnosis of coronary artery disease (CAD) and provides information for further intervention. Fractional Flow Reserve (FFR) at the time of ICA is the gold standard to analyze the hemodynamic and physiologic significance of moderate coronary stenosis. The dawn of coronary CT angiography (CTA) has helped in visualizing the anatomy of coronary arteries. Computed Fractional Flow Reserve (FFRCT) from such an imaging study shows promise in providing valuable data about physiology on top of the anatomy noninvasively; which can guide decision-making process for revascularization. This manuscript aims to review the accuracy of FFRCT obtained from a coronary CTA in the diagnosis of hemodynamically significant coronary artery stenosis and ruling out nonsignificant coronary artery stenosis when compared to the Gold standard of FFR obtained during ICA. We conducted a Medline search using various combinations of "FFRCT," "ICA" "noninvasive," "significant stenosis," and "CAD" to identify pivotal randomized trials published before May 1, 2020, for inclusion in this review. Concurrently, major practice guidelines, trial bibliographies, and pertinent reviews were examined to ensure inclusion of relevant trials. A consensus among the authors was used to choose items for narrative inclusion. The following section reviews data from pivotal trials to determine a noninvasive strategy in appropriate patients to accurately detect functionally significant stenosis. For these trials, the sensitivity, specificity, and accuracy are compared. Trials reviewed: CTA, FFRCT, ICA, CT-myocardial perfusion imaging. FFRCT is a novel noninvasive modality which localizes significant "ischemia-causing" stenosis (≤0.80) by means of crystal fluid dynamics eliminating the need for vasodilators. The analysis of FFRCT by DISCOVER FLOW, DeFACTO, NXT trials revealed high sensitivity, negative predictive value, and good accuracy. The ADVANCE registry showed significantly lower events of CV death or myocardial infarction with a negative FFRCT (>0.80 study). The PLATFORM trial showed significant reduction in negative ICA with negative FFRCT, thus ultimately reducing the number of unnecessary percutaneous coronary intervention. Decrease in healthcare costs was noted with FFRCT, decreasing downstream testing, and invasive procedures. FFRCT is a novel modality for analyzing significant stenosis in CAD noninvasively. The high sensitivity of this modality could make it a good rule out tool to avoid unnecessary intervention in physiologically insignificant lesions. Limitations of this modality include low specificity, double exposure to contrast, turnaround time, and upfront costs. Further query into this matter is warranted.

Patient-reported financial barriers to adherence to treatment in neurology.

OBJECTIVE: Many effective medical therapies are available for treating neurological diseases, but these therapies tend to be expensive and adherence is critical to their effectiveness. We used patient-reported data to examine the frequency and determinants of financial barriers to medication adherence among individuals treated for neurological disorders. PATIENTS AND METHODS: Patients completed cross-sectional surveys on iPads as part of routine outpatient care in a neurology clinic. Survey responses from a 3-month period were collected and merged with administrative sources of demographic and clinical information (eg, insurance type). We explored the association between patient characteristics and patient-reported failure to refill prescription medication due to cost in the previous 12 months, termed here as "nonadherence". RESULTS: The population studied comprised 6075 adults who were presented between July and September 2015 for outpatient neurology appointments. The mean age of participants was 56 (standard deviation: 18) years, and 1613 (54%) were females. The patients who participated in the surveys (2992, 49%) were comparable to nonparticipants with respect to gender and ethnicity but more often identified English as their preferred language (94% vs 6%, p<0.01). Among respondents, 9.8% (n=265) reported nonadherence that varied by condition. These patients were more frequently Hispanic (16.7% vs 9.8% white, p=0.01), living alone (13.9% vs 8.9% cohabitating, p<0.01), and preferred a language other than English (15.3% vs 9.4%, p=0.02). CONCLUSION: Overall, the magnitude of financial barriers to medication adherence appears to vary across neurological conditions and demographic characteristics.

Feasibility of the collection of patient-reported outcomes in an ambulatory neurology clinic.

OBJECTIVE: To determine whether patients could self-report physical and mental health assessments in the waiting room and whether these assessments would be associated with modified Rankin Scale (mRS) and Quality of Life in Epilepsy (QOLIE-10) scores. METHODS: We offered iPad-based surveys to consecutive adult neurology patients at check-in to collect patient-reported outcome measures (PROMs). We collected demographic and clinical data on 6,075 patients through survey or administrative claims and PROMs from participating patients. We compared demographic characteristics of participants and nonparticipants and tested associations between physical and mental health scores and mRS and QOLIE-10. RESULTS: Of 6,075 patients seen by neurologists during the study period, 2,992 (49.3%) participated in the survey. Compared to nonparticipating patients, participating patients more often were privately insured (53.5% vs 42.7%, p < 0.01), married (51.5% vs 47.9%, p < 0.01), and seen in general neurology (nonsubspecialty) clinics (53.1% vs 46.6%, p < 0.01) and more likely to report English as their preferred language (50.1% vs 38.4%, p < 0.01). Participating patients had a mean physical health T score of 28.7 (SD 15) and mental health T score of 33 (SD 15), which were 3 and 2 SD worse than the average for the US general population, respectively. Mean T scores in every category of the mRS were different from every other category (n = 232, p < 0.01). Patient Reported Outcomes Measurement Information System-10 T scores were linearly associated with QOLIE-10 scores (n = 202, p < 0.01) CONCLUSIONS: Systematic digital collection of PROMs is feasible. Differences among survey participants and nonparticipants highlight the need to develop multilingual measurement tools that may improve collection from vulnerable populations.

Patient perceptions of physician-documented quality care in epilepsy.

OBJECTIVE: The aim of this study was to compare physician encounter documentation with patient perceptions of quality of epilepsy care and examine the association between quality and patient assessment of provider communication. METHODS: We identified 505 adult patients with epilepsy aged 18years or older over a 3-year period in two large academic medical centers. We abstracted individual, clinical, and care measures from 2723 electronic clinical notes written by physicians. We then randomly selected 245 patients for a phone interview. We compared patient perceptions of care with the documented care for several established epilepsy quality measures. We also explored the association of patient's perception of provider communication with provider documentation of key encounter interventions. RESULTS: There were 88 patients (36%) who completed the interviews. Fifty-seven (24%) refused to participate, and 100 (40%) could not be contacted. Participants and nonparticipants were comparable in their demographic and clinical characteristics; however, participants were more often seen by epilepsy specialists than nonparticipants (75% vs. 61.9%, p<0.01). Quality scores based on patient perceptions differed from those determined by assessing the documentation in the medical record for several quality measures, e.g., documentation of side effects of antiseizure therapy (p=0.05), safety counseling (p<0.01), and counseling for women of childbearing potential with epilepsy (McNemar's p=0.03; intraclass correlation coefficient, ICC=0.07). There was a significant, positive association between patient-reported counseling during the encounter (e.g., personalized safety counseling) and patient-reported scores of provider communication (p=0.05). CONCLUSIONS: The association between the patient's recollection of counseling during the visit and his/her positive perception of the provider's communication skills highlights the importance of spending time counseling patients about their epilepsy and not just determining if seizures are controlled.