Citations

Abstract Background In patients with newly diagnosed glioblastoma, rapid early progression (REP) refers to tumor regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis appraised previously published data on REP to better characterize and understand it. Methods Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to October 21, 2021. Studies describing the incidence of REP—tumor growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly diagnosed glioblastoma were included. The primary outcome was REP incidence. Results From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0–58.8 y). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1–1.5). The median number of days between MRI scans was 34 days (IQR 18–45 days). The mean incidence rate of REP was 45.9% (range 19.3%–72.0%) and significantly lower in studies employing functional imaging to define REP (P < .001). REP/non-REP groups were comparable with respect to age (P = .99), gender (P = .33) and time between scans (P = .81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30–2.43, P < .001), shortened progression-free survival (HR 1.78, 95% CI 1.30–2.43, P < .001), subtotal resection (OR 6.96, 95% CI 4.51–10.73, P < .001) and IDH wild-type versus mutant tumors (OR 0.20, 95% CI 0.02–0.38, P = .03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72–2.28, P = .39). Conclusions REP occurs in almost half of patients with newly diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.

Introduction: Primary care clinicians are presented with hundreds of new clinical recommendations and guidelines. To consider practice change clinicians must identify relevant information and develop a contextual framework. Too much attention to information irrelevant to one’s practice results in wasted resources. Too little results in care gaps. A small group of primary care clinicians in a large health system sought to address the problem of vetting new information and providing peer reviewed context. This was done by engaging colleagues across the system though a primary care learning collaborative. Methods: The collaborative was a grass roots initiative between community and academic-based clinicians. They invited all the system’s primary care clinicians to participate. They selected new recommendations or guidelines and used surveys as the principal communication instrument. Surveys shared practice experience and also invited members to give narrative feedback regarding their acceptance of variation in care relate to the topic. A description of the collaborative along with its development, processes, and evolution are discussed. Process changes to address needs during the COVID-19 pandemic including expanded information sharing was necessary. Results: Collaborative membership reached across 5 states and included family medicine, internal medicine, and pediatrics. Members found involvement with the collaborative useful. Less variation in care was thought important for public health crises: the COVID pandemic and opioid epidemic. Greater practice variation was thought acceptable for adherence to multispecialty guidelines, such as diabetes, lipid management, and adult ADHD care. Process changes during the pandemic resulted in more communications between members to avoid practice gaps. Conclusion: An internet-based learning collaborative in a health system had good engagement from its members. Using novel methods, it was able to provide members with feedback related to the importance of new practice recommendations as perceived by their peers. Greater standardization was thought necessary when adopting measures to address public health crisis, and less necessary when addressing multispecialty guidelines. By employing a learning collaborative, this group was able to keep members interested and engaged. During the first year of the COVID pandemic the collaborative also served as a vehicle to share timely information.

Abstract Digital technology is now an integral part of medicine. Tools for detecting, screening, diagnosis, and monitoring health-related parameters have improved patient care and enabled individuals to identify issues leading to better management of their own health. Wearable technologies have integrated sensors and can measure physical activity, heart rate and rhythm, and glucose and electrolytes. For individuals at risk, wearables or other devices may be useful for early detection of atrial fibrillation or sub-clinical states of cardiovascular disease, disease management of cardiovascular diseases such as hypertension and heart failure, and lifestyle modification. Health data are available from a multitude of sources, namely clinical, laboratory and imaging data, genetic profiles, wearables, implantable devices, patient-generated measurements, and social and environmental data. Artificial intelligence is needed to efficiently extract value from this constantly increasing volume and variety of data and to help in its interpretation. Indeed, it is not the acquisition of digital information, but rather the smart handling and analysis that is challenging. There are multiple stakeholder groups involved in the development and effective implementation of digital tools. While the needs of these groups may vary, they also have many commonalities, including the following: a desire for data privacy and security; the need for understandable, trustworthy, and transparent systems; standardized processes for regulatory and reimbursement assessments; and better ways of rapidly assessing value.

Background: Conduction tissue in the ventricles is closely intertwined with myocardium. Owing to high velocity of conduction, there is near simultaneous activation , making it difficult to discern. Restricted sampling rates and limited dynamic range make real time signal processing challenging for these signals in routine recording systems. Objectives: We aimed to use novel signal processing techniques in a new system to isolate the conduction tissue signals from the rest of the myocardial activation. Methods: We used the PURE-EP™ (BioSig Technologies, MN) signal processing system to record endocardial and epicardial signals from 6 anesthetized canines in an acute study setting. A novel filter based on proprietary algorithms to isolate the high frequency signal was applied at sites where the electrogram signals were thought to have a conduction tissue component to them. . In addition, ventricular fibrillation (VF) was induced at the end of the experiment and signals were then recorded from the endocardium and the conduction system. Results: This filter was successfully able to isolate conduction tissue signals in the myocardium from those of the ventricular muscle. It did over sense atrial signals at the basal left ventricular septum owing to the high frequency components of the atrial signal at this location. When applied to epicardial signals, it did not pick up any conduction tissue signals. In VF, we could discern signals originating from the conduction system endocardially. (Figure 1) Conclusions: This filter can isolate conduction tissue signals from those of the myocardium and may prove to be a useful adjunct in mapping arrhythmias originating near the conduction system.

Background: Ablation in the sinuses of Valsalva (SoV) within the aorta is fraught with risk, owing to the proximity of the coronary arteries. Assessment of catheter tip position is not very easy at this location owing to complex local anatomy and poor images from available modalities. Objectives: We propose the use of novel local unipolar electrogram characteristics using a new signal recording system to guide the assessment of catheter tip position in this region. Methods: We recorded unipolar signals from above the SoV, within the coronaries and below the SoV using the PURE-EP™ (BioSig Technologies, MN) signal processing system in 4 anesthetized canines in the setting of an acute study. We used fluoroscopy, intracardiac echocardiography and angiography for confirmation of the position of the catheter tip. We recorded changes in the signals when transitioning between (1) the coronary arteries and the SoV and (2) the SoV and below the SoV. Results: The unipolar signal showed a negative current of injury (COI) when the catheter tip was present in the SoV, whereas within the coronary artery or below the SoV, the COI was positive. We propose that the difference in the distribution of ventricular muscle below and above the SoV is responsible for this phenomenon. These changes in the COI were noted immediately when transitioning from one location to another and were present reproducibly in all the dogs. ( Figure 1 ) Conclusions: Analysis of the changes on the local electrogram can provide information about the location of the catheter tip which could prove critical in saving lives.

Background Patients with single ventricle (SV) congenital heart disease (CHD) undergo several interventions in the first years of life. Advanced diagnostics are required for interstage assessment of anatomy, but are associated with significant diagnostic risk. We sought to evaluate image quality, risk, and accuracy of cardiac computed tomography (CCT) for evaluation of anatomy prior to superior cavopulmonary connection (SCPC) compared to surgical findings across 2 institutions. Methods A retrospective evaluation of image quality, risk, and accuracy of pre-SCPC CCT was performed at 2 institutions between January 1, 2010 and September 30, 2016. Results CCT was performed in 90 SV CHD patients with a median age of 4.03 months (interquartile range [IQR] 3.36, 5.33) prior to SCPC. Image quality was optimal (84%) or good (16%) in all patients, without significant discrepancy compared to surgical findings. 7 patients (8%) required interventional cardiac catheterization subsequent to CCT and before surgical intervention. 49% of scans were performed without sedation, 43% of scans were performed with mild to moderate sedation, and 8% of scans were performed with general anesthesia. The median total procedural dose-length product (DLP) was 18 (IQR 14, 26) mGy*cm, estimating an age adjusted radiation dose of 1.4 millisievert (mSv). One minor (1%) adverse event was reported within 24 h of the CCT. Surgical complications were unrelated to the presurgical findings. Conclusions CCT for pre-SCPC evaluation is safe, with excellent accuracy for anatomy at the time of surgical intervention across 2 institutions. In select patients, noninvasive evaluation with CCT may be indicated.

AbstractSince vaccination for SARS‐CoV‐2 coronavirus started, the trajectory of patient numbers infected with the virus has improved once; however, variants of SARS‐CoV‐2 have emerged and more people have been infected; therefore, pandemic status is still far from resolution. Government and social efforts to prevent coronavirus infection continue in most states in the US and globally even after the Centers for Disease Control and Prevention declared some restriction relief for fully vaccinated people in March 2021. Healthcare institutions and various professional organizations have developed guidelines or policies to prevent the spread of these coronaviruses in the setting of apheresis. In this report, the issues that apheresis services may encounter under the current COVID‐19 (SARS‐CoV‐2 coronavirus disease) pandemic will be discussed with potential strategies that can be adapted for efficient and optimum use of apheresis resources.

Background: The use of direct current electroporation has the potential for significant utility because of its non-thermal approach to tissue destruction. However, the fear of inducibility of cardiac arrhythmias (particular ventricular fibrillation) when using electroporation remains of concern due to membrane poration and ion flux during periods of vulnerability occurring in ventricular repolarization. Objectives: Critically examine the incidence of arrhythmias in a series of acute canine studies to retrospectively determine cause and safe electoporative dosing margins. Methods: We performed electroporation ablation in 6 acute canine studies. These were experimental studies performed at sites critical in arrhytmogenesis. Sites included the pulmonary veins, left atrial appendage, superior vena cavae, right atrium and ventricle. Electroporation was delivered using an ECG gating algorithm so that QRS complexes are tagged and direct current energy is not delivered during the vulnerable portion of the T wave. Results: In 6 acute canine experiments, we delivered a total of 62 electroporation applications for ablation purposes. The average electroporation dosage delivered involved an average of 1427 Volts (range 750-3000 V), Pulse length of 100 ms, and number of pulses of 20.2 (range 10-100). AF was induced in 27.4% of electroporiatve applications. Atrial flutter/tachycardia occurred in 8.1%. VF occurred in only one application at a location of the left superior pulmonary vein. Conclusion: These data suggest that induction of VF is relatively uncommon with ECG gating and highlight its importance when using this modality. However, the induction of AF occurs with higher frequency. The actual mechanism as to why this occurs requires further systematic study.

Introduction: Right ventricular apical (RVA) pacing appears to have detrimental effects on cardiac function and long term outcomes. Right ventricular non-apical (RVNA) pacing, especially in the septal position, has been postulated as an alternative that may lead to less morbidity and mortality. Prior studies have shown conflicting results and been limited by small numbers and short follow-up. We aimed to determine if right ventricular septal lead position was associated with a reduction in long-term mortality compared to RVA lead position. Methods: Patients who underwent dual-chamber pacemaker implantation from 2004 through 2013 were evaluated for right ventricular lead position based on chest radiographs. Lead positions were divided in to apical or non-apical. Non-apical lead positions were subdivided to isolate a septal lead position group. Mortality was compared between these groups. Results: During the study period, 3456 patients underwent dual-chamber pacemaker placement and had images appropriate for lead position evaluation. The group was 53.5% male with a mean age of 74 ± 13 years. RVNA lead position was found in 976 (28.2%) patients, including 243 (7.0%) with a septal position. There was no significant difference in age or prior heart failure diagnosis between groups. Kaplan-Meier survival analysis did not reveal a significant difference in mortality between patients with RVA versus RVNA lead position during 5 year follow-up (p = 0.82). However, septal lead position was associated with a significantly lower mortality compared with RVA position (p = 0.03) (figure). Conclusions: Right ventricular septal lead position is associated with a lower long-term mortality than RVA lead position. This has substantial implications regarding the preferred site for ventricular pacing lead placement.

Introduction: Counteracting the pandemic of peripheral vascular disease necessitates development of proangiogenic treatments. As stem cell benefit has increasingly been associated with paracrine influence on diseased tissue, a purified extracellular vesicle population (PEP) was established to promote tissue regeneration and neovascularization. The mechanistic basis for PEP-induced proangiogenic effects was here probed and validated in two separate in vivo models of vascular ischemia. Hypothesis: PEP drives pro-angiogenic effects though donation of VEGFR. Methods: Nanosight and immunoblotting were utilized to characterize PEP purity and identity. OMICs profiling identified VEGFR as highly prioritized, with downstream signaling was tested in human umbilical vascular endothelial cells using Matrigel assay, qPCR and immunoblotting. In vivo, blood perfusion (Fluorescent imaging - SPY) was quantified in a rodent model of hind-limb ischemia and in a rabbit model of critical ischemic ear, each treated with sham or PEP. Rabbit tissues were next examined by whole transcriptome analysis to assess PEP-induced proangiogenic signaling. Immunohistochemical staining with smooth muscle actin and von Willebrand factor probed de novo blood vessel formation. Results: PEP was characterized by size (mean: 128.6 +/-1 nm) and VEGFR expression. VEGFR knock-down diminished endothelial cell angiogenic activity in vitro, rescued with PEP (5.3x1010+/-109 vesicles/ml) was sufficient enhance total and phosphor-VEGFR expression, along with amplification of downstream VEGFR targets (MAPK, AKT, CXCL8, NOTCH4, MMP9) and enhanced tube formation. In both hind-limb (n=5) and critical ear (n=4) ischemia models, local delivery of PEP to ischemic tissue resulted in restoration of blood perfusion and prioritized proangiogenic signaling in tissue transcriptome pathway analysis, further confirmed by immunohistochemistry. Conclusions: Taken together, our study establishes a new regenerative paradigm documenting exosome-based delivery of VEGFR as a key driver for angiogenesis. This PEP-based platform broadens potential options available for treatment of peripheral vascular disease and may have therapeutic implications in restoration of microvasculature.