Citations

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.

Thrombin plays a major role in coagulation cascade and participates in regulation of vascular function through its effects on protease-activated receptors (PARs). The effect of thrombin inhibition on vascular and aortic valve function during prolonged hypercholesterolemia, however, remains unknown. In the present study, we tested the hypothesis that direct thrombin inhibition (DTI, dabigatran etexilate) slows progression of endothelial and aortic valve dysfunction in ldlr-deficient, apolipoprotein B100-only (LA) mice. Carotid arteries from LA mice were used for studies of endothelial function in isolated organ baths, and aortic valve function was evaluated using echocardiography. In placebo-treated mice, maximum relaxation to acetylcholine was reduced following 6 and 9 months of hypercholesterolemia (maximum relaxation to acetylcholine (MR ACH ) =75%± 3.7, and 67%± 3.6, respectively), but not affected by DTI (75%± 2.5, and 62%± 3.2, respectively). Relaxation to exogenous NO donors was also unaffected by DTI. Aortic valve function progressively deteriorated at 3, 6, and 9 months in placebo-treated mice (2.1 m/s± 0.04, 2.5 m/s± 0.1, and 2.9m/s ± 0.1, respectively), and was not affected by DTI (2.0m/s± 0.1, 2.5m/s± 0.1 and 3.0m/s ± 0.4, respectively). While PAR receptor expression was detected in aorta and aortic valve tissue, expression of SPHK1 (an indicator of PAR1 activity) was not altered by DTI. Expression of CTGF in aortic valves, however, tended to be reduced by DTI. In conclusion, our data suggest that DTI does not prevent vasomotor or aortic valve dysfunction in mice with prolonged hypercholesterolemia, but may attenuate pro-fibrotic signaling in aortic valves.

Adverse childhood experiences (ACEs) are potentially traumatic events that can cause lifelong suffering, with 1 out of 2 children in the United States experiencing at least 1 ACEs. The intergenerational effect of ACEs has been described, but there’s still paucity of knowledge of its impact on child development and behavior in children enrolled in Early Head Start (EHS) home visiting programs. A retrospective observational study was performed with 71 parents and 92 children participating in the EHS Home Visiting Program in Olmsted County from 2014 to 2019. Parents reported their own ACEs using a 10-item questionnaire. Children’s social-emotional status was evaluated with Devereux Early Childhood Assessment Second Edition (DECA) and development was evaluated using the Brigance Early Childhood Screens III. Referrals of children by EHS staff to community agencies were recorded. The association between parental ACEs score, developmental outcomes and referrals was analyzed. Parental ACEs score of 4 or more was associated with failing at least 1 domain on the Brigance screen ( P = .02) especially adaptive/cognitive domain ( P = .05), and increased risk of referral to community resources ( P < .001). However, there was no association between ACEs scores and failing DECA screens. We identified an intergenerational association between parental exposure to ACEs and risk for childhood developmental delay and referrals to community services. Parental adverse childhood experiences (ACEs) have intergenerational effects on offspring. In our study, parental ACEs are associated with offspring developmental delays and referral to community resources. Screening for parental adverse childhood experiences, a key social determinant of health, is imperative and should be incorporated into primary care and early childhood settings to identify children at risk for developmental delay.

AbstractIntroductionPatients with small‐cell lung cancer (SCLC) have a very poor prognosis. However, a subset of SCLC achieves long‐term survival. The objective of this study was to investigate factors and pattern of long‐term survival in patients with limited‐stage small cell lung cancer (LS‐SCLC) who achieved a complete response (CR) after chemoradiotherapy.Patient and MethodsThis was a single‐center retrospective study. The analysis of hazard ratio (HR) and 95% confidence interval (CI) was performed using Cox proportional hazards model. For pattern analysis, the date of recurrence was used as the endpoint. The nominal categorical variables were analyzed by the χ2 test. Survival was estimated using the Kaplan–Meier model, and the results were reported as the median and interquartile range.ResultsWe identified 162 patients, median age was 64.7 (56.2–70.2) years, and 94 (58%) were females. Eighty‐one patients (50%) had recurrence during follow‐up. Gastroesophageal reflux disease (GERD) (HR, 0.65; 95% CI, 0.45–0.93; p = 0.016) and neurological paraneoplastic syndrome (PNS) (HR, 0.46; 95% CI, 0.29–0.72; p < 0.001) were independent factors associated with improved overall survival (OS). Patients with GERD had prolonged recurrence free survival (RFS) compared to patients without GERD (median, 29.1 months vs. 13.9 months, p < 0.001), whereas patients with neurological PNS had a reduced recurrence rate compared to those patients without neurological PNS (No. [%], 8 [20.5] vs. 73 [59.3], p < 0.001).ConclusionsPatients with LS‐SCLC achieving a CR after chemoradiotherapy, GERD, and neurological PNS were associated with improved OS. GERD and neurological PNS were associated with longer RFS and lower recurrence rate, respectively.

AbstractBackgroundUp to 30% of frontotemporal dementia (FTD) cases are due to known pathogenic mutations (f‐FTD). Little is known about the factors that predict who will choose to learn their results. Upcoming clinical trials in f‐FTD may require disclosure prior to enrollment, even before symptom onset, and thus characterizing this sample is important. Furthermore, understanding the mood impacts of genetic disclosure may guide genetic counseling practice.MethodF‐FTD participants (n=568) from families with a known pathogenic mutation (MAPT, C9orf72, GRN) were enrolled through the ARTFL/LEFFTDS Longitudinal FTD Study (ALLFTD) and provided the opportunity for disclosure. Independent‐sample t‐tests compared demographic and psychosocial factors between participants who did and did not receive their results. In participants who were asymptomatic at baseline and follow up (n=199,177 with follow‐up), linear mixed effects modeling was used to investigate pre‐ to post‐disclosure changes in the 15‐item Geriatric Depression Scale (GDS).ResultOf participants from families with a known pathogenic genetic mutation, 47% received genetic disclosure. Of the asymptomatic subset (n=386), 36% know their mutation status. Of these asymptomatic learners, 46% received disclosure through the study, and the remainder learned their genetic status prior to study enrollment. None of the analyzed demographic or psychosocial factors (i.e., sex, age, education, having children) differed between learners and non‐learners (p’s > 0.05). In the longitudinal analysis of asymptomatic participants, learners showed a pre‐ to post‐increase of 0.31 GDS points/year (95%CI: ‐0.08, 0.69, p = 0.12), whereas non‐learners showed a slight decline (‐0.15 points/year, 95%CI: ‐0.36, 0.06, p = 0.16). This difference between slopes was statistically significant (0.46, 95%CI: 0.02, 0.89, p=0.04) but represents a small clinical effect. In asymptomatic learners, slopes did not differ based on mutation status (0.28, 95%CI: ‐0.66, 1.20, p=0.55). Conclusions were based on the estimates and full range of confidence intervals.ConclusionThe majority of asymptomatic research participants do not know their genetic status, which will be a consideration for clinical trials that require disclosure. No considered demographic factors were strongly associated with the decision to receive disclosure. The findings suggest that disclosure in asymptomatic participants has minimal impact on depressive symptoms regardless of genetic results.

Abstract The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.