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2.
Heart Rhythm ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38752909

ABSTRACT

BACKGROUND: Because of differences in chest wall anatomy, female patients may have higher rates of subcutaneous implantable cardioverter-defibrillator (S-ICD) pocket-related complications. OBJECTIVE: We sought to evaluate sex-based outcomes after S-ICD implantation. METHODS: Patients implanted with an S-ICD at Emory Healthcare between 2010 and 2023 were included in the analysis. Patients' clinical characteristics and post-S-ICD implantation complications were collected. RESULTS: There were 429 male patients (68%) and 199 female patients (32%) observed for a median duration of 2.3 years (0.6-4.4 years). Male and female patients had comparable rates of diabetes (28%), end-stage renal disease (29.5%), ejection fraction (30.2% ± 13.4%), and body mass index (29.1 ± 6.6 kg/m2). There was no statistical difference in the incidence of shocks between men and women (26.3% vs 20.1%; P = .09), including appropriate shocks (14.7% vs 12%; P = .98) and inappropriate shocks (11.7% vs 9.5%; P = .98). Pocket-related complications occurred in 21 patients; these included pocket infection (n = 12), wound dehiscence (n = 7), and hematoma requiring drainage (n = 2). Female patients had a significantly higher pocket-related complication rate compared with male patients (7.2% vs 2.5%; P = .016). In controlling for age, body mass index, diabetes, and end-stage renal disease, female patients had higher odds of pocket-related complications compared with male patients (odds ratio, 3.15; 95% confidence interval, 1.27-7.75). Pocket-related complications decreased after 2018 compared with before 2018 (6% vs 2.6%, P = .052), mainly driven by reduction in complications in women (12.3% vs 3.2%; P = .034) but not in men (2.8% vs 2.4%; P = 1). CONCLUSION: In this cohort of S-ICD patients, women had a higher rate of post-S-ICD pocket-related complications that could be explained by sex-based differences in anatomy.

3.
Res Sq ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38562878

ABSTRACT

The germinal center (GC) dark zone (DZ) and light zone (LZ) regions spatially separate expansion and diversification from selection of antigen-specific B-cells to ensure antibody affinity maturation and B cell memory. The DZ and LZ differ significantly in their immune composition despite the lack of a physical barrier, yet the determinants of this polarization are poorly understood. This study provides novel insights into signals controlling asymmetric T-cell distribution between DZ and LZ regions. We identify spatially-resolved DNA damage response and chromatin compaction molecular features that underlie DZ T-cell exclusion. The DZ spatial transcriptional signature linked to T-cell immune evasion clustered aggressive Diffuse Large B-cell Lymphomas (DLBCL) for differential T cell infiltration. We reveal the dependence of the DZ transcriptional core signature on the ATR kinase and dissect its role in restraining inflammatory responses contributing to establishing an immune-repulsive imprint in DLBCL. These insights may guide ATR-focused treatment strategies bolstering immunotherapy in tumors marked by DZ transcriptional and chromatin-associated features.

4.
J Cardiovasc Electrophysiol ; 35(5): 929-938, 2024 May.
Article in English | MEDLINE | ID: mdl-38450808

ABSTRACT

INTRODUCTION: Transvenous leads have been implicated in tricuspid valve (TV) dysfunction, but limited data are available regarding the effect of extracting leads across the TV on valve regurgitation. The aim of this study is to quantify tricuspid regurgitation (TR) before and after lead extraction and identify predictors of worsening TR. METHODS: We studied 321 patients who had echocardiographic data before and after lead extraction. TR was graded on a scale (0 = none/trivial, 1 = mild, 2 = moderate, 3 = severe). A change of >1 grade following extraction was considered significant. RESULTS: A total of 321 patients underwent extraction of a total of 338 leads across the TV (1.05 ± 0.31 leads across the TV per patient). There was no significant difference on average TR grade pre- and postextraction (1.18 ± 0.91 vs. 1.15 ± 0.87; p = 0.79). TR severity increased after extraction in 84 patients, but was classified as significantly worse (i.e., >1 grade change in severity) in only 8 patients (2.5%). Use of laser lead extraction was associated with a higher rate of worsening TR postextraction (44.0% vs. 31.6%, p = 0.04). CONCLUSION: In our single-center analysis, extraction of leads across the TV did not significantly affect the extent of TR in most patients. Laser lead extraction was associated with a higher rate of worsening TR after extraction.


Subject(s)
Device Removal , Tricuspid Valve Insufficiency , Humans , Tricuspid Valve Insufficiency/physiopathology , Tricuspid Valve Insufficiency/surgery , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/etiology , Tricuspid Valve Insufficiency/diagnosis , Male , Female , Device Removal/adverse effects , Aged , Treatment Outcome , Middle Aged , Retrospective Studies , Risk Factors , Severity of Illness Index , Tricuspid Valve/physiopathology , Tricuspid Valve/surgery , Tricuspid Valve/diagnostic imaging , Defibrillators, Implantable , Time Factors , Pacemaker, Artificial , Aged, 80 and over , Cardiac Resynchronization Therapy Devices
5.
Nat Commun ; 15(1): 2113, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459052

ABSTRACT

Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Humans , Prognosis , Lymphoma, Large B-Cell, Diffuse/pathology , Gene Expression Profiling , Transcriptome , Germinal Center/pathology , Tumor Microenvironment/genetics
6.
Front Oncol ; 14: 1307839, 2024.
Article in English | MEDLINE | ID: mdl-38347838

ABSTRACT

Deregulation of the DNA damage response (DDR) plays a critical role in the pathogenesis and progression of many cancers. The dependency of certain cancers on DDR pathways has enabled exploitation of such through synthetically lethal relationships e.g., Poly ADP-Ribose Polymerase (PARP) inhibitors for BRCA deficient ovarian cancers. Though lagging behind that of solid cancers, DDR inhibitors (DDRi) are being clinically developed for haematological cancers. Furthermore, a high proliferative index characterize many such cancers, suggesting a rationale for combinatorial strategies targeting DDR and replicative stress. In this review, we summarize pre-clinical and clinical data on DDR inhibition in haematological malignancies and highlight distinct haematological cancer subtypes with activity of DDR agents as single agents or in combination with chemotherapeutics and targeted agents. We aim to provide a framework to guide the design of future clinical trials involving haematological cancers for this important class of drugs.

7.
Europace ; 25(12)2023 12 06.
Article in English | MEDLINE | ID: mdl-38000900

ABSTRACT

AIMS: Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports. METHODS AND RESULTS: We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction. CONCLUSION: DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.


Subject(s)
Defibrillators, Implantable , Humans , Defibrillators, Implantable/adverse effects , Equipment Failure , Retrospective Studies
8.
Europace ; 25(12)2023 12 06.
Article in English | MEDLINE | ID: mdl-38006390

ABSTRACT

AIMS: The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. METHODS AND RESULTS: We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.


Subject(s)
Heart Ventricles , Heart , Humans , Arrhythmias, Cardiac , Ventricular Fibrillation/surgery , Action Potentials/physiology
9.
Cureus ; 15(9): e46158, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37905249

ABSTRACT

Introduction Research on the healthcare available to young adults in India is negligible. There is little to no data available to describe the Indian young adults' knowledge and attitude toward a doctor-patient interaction and their perceptions on what might be a barrier to confidentiality. Young adults in India, often face the unique dilemma of being old enough to make their own medical decisions and yet often finding themselves without the freedom or knowledge to do so. Understanding factors that young adults perceive to be affecting confidentiality and a barrier in their healthcare checkups can greatly improve the quality of healthcare provided to them. Objective The objective of the study was to assess knowledge and attitudes among young adults in Bangalore City regarding the maintenance of confidentiality by a doctor while seeking healthcare and to identify perceived factors the young adults believed to be affecting confidentiality and information disclosure when seeking healthcare.  Method A cross-sectional, descriptive study was carried out using multi-stage random sampling. Four colleges were randomly selected from four geographic zones in Bangalore City (North, East, South, and West). The investigators developed a 30-question questionnaire, comprising sections on patient details, perceptions regarding confidentiality, factors influencing history disclosure, etc., which was validated by a panel of four faculty members from one para-clinical and two clinical departments each, belonging to the investigators' medical college. Subsequently, a pilot study with 33 participants was conducted and a sample size of 60 was arrived at assuming an 83.87% favorable knowledge regarding the right to refuse to disclose information to a doctor, with a 95% confidence interval and a 10% absolute allowable error. Further validation was done following the pilot study. Student lists from the chosen colleges were obtained, and the required sample size was distributed based on probability proportional to size (PPS): 19, 19, 12, and 10 participants from the respective colleges. Random number tables were utilized to select the required number of participants from the student population. The participants of the pilot study were not included in the study. The questionnaire was administered digitally by the investigators, and in cases where a student declined to participate, an alternative participant was chosen using random number tables.  Results Results demonstrate that 21.7% (13) of respondents were unaware that a doctor is legally bound to keep details of the visit confidential. A total of 93.3% (56) of the respondents report that a parent/guardian plays an active role in their doctor's visit. Only 16.7% (10) of respondents strongly agreed that they felt comfortable enough to have an honest conversation with their doctor. Respondents report that they were most likely to withhold history regarding sexual practices (55%), alcohol use (35%), and smoking (31.7%). Conclusion  Healthcare providers should take all possible measures to ensure confidential and quality care to the vulnerable young adult population. Breach of confidentiality, often in the form of a parent or guardian being present during the history-taking process. can be a barrier to building good rapport and negatively impact the doctor-patient relationship.

10.
medRxiv ; 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37662394

ABSTRACT

Background: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., periods 4, 6, 8,...) are expected but have minimal experimental evidence. Methods: We studied explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Optical mapping of the transmembrane potential was performed after staining the hearts with voltage-sensitive fluorescent dyes. Hearts were stimulated at an increasing rate until VF was induced. Signals recorded from the right ventricle endocardial surface prior to induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results were correlated to the underlying electrophysiological characteristics as quantified by restitution curves and conduction velocity. Results: A prominent and statistically significant global 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. Discussion: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts. We infer from the independence of the period to the underlying restitution properties that the oscillation of the excitation-contraction coupling and calcium cycling mechanisms is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation and may provide targets for substrate-based ablation of VF.

11.
Blood Cancer J ; 13(1): 140, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37679351

ABSTRACT

Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.


Subject(s)
Waldenstrom Macroglobulinemia , Humans , Waldenstrom Macroglobulinemia/drug therapy , Rituximab/adverse effects , Bortezomib , Clinical Protocols , Cyclophosphamide
12.
J Cardiovasc Electrophysiol ; 34(11): 2225-2232, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37702135

ABSTRACT

INTRODUCTION: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre-existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score. METHODS: We prospectively evaluated all patients without pre-existing pacemakers, ICD, or pre-existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision-making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis. RESULTS: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05-3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74-0.88], p < 0.001). CONCLUSIONS: The ERS prospectively predicted the need for PPM in a serial, real-world cohort of patients undergoing TAVR with a balloon-expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Pacemaker, Artificial , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Retrospective Studies , Cardiac Pacing, Artificial/adverse effects , Cardiac Pacing, Artificial/methods , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Treatment Outcome , Risk Factors , Aortic Valve/diagnostic imaging , Aortic Valve/surgery
13.
South Med J ; 116(9): 745-749, 2023 09.
Article in English | MEDLINE | ID: mdl-37657781

ABSTRACT

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic disrupted how educational conferences were delivered, leaving programs to choose between in-person and virtual morning report formats. The objective of our study was to describe morning reports during the COVID-19 pandemic, including the use of virtual formats, attendance, leadership, and content. METHODS: A prospective observational study of morning reports was conducted at 13 Internal Medicine residency programs between September 1, 2020 and March 30, 2021, including a follow-up survey of current morning report format in January 2023. RESULTS: In total, 257 reports were observed; 74% used virtual formats, including single hospital, multiple hospital, and a hybrid format with both in-person and virtual participants. Compared with in-person reports, virtual reports had more participants, with increased numbers of learners (median 21 vs 7; P < 0.001) and attendings (median 4 vs 2; P < 0.001), and they were more likely to involve medical students (83% vs 40%; P < 0.001), interns (99% vs 53%; P < 0.001), and program directors (68% vs 32%; P < 0.001). Attendings were less likely to lead virtual reports (3% vs 28%, P < 0.001). Virtual reports also were more likely to be case based (88% vs 69%; P < 0.001) and to use digital presentation slides (91% vs 36%; P < 0.001). There was a marked increase in the number of slides (median 20 vs 0; P < 0.001). As of January 2023, all 13 programs had returned to in-person reports, with only 1 program offering an option to participate virtually. CONCLUSIONS: During the COVID-19 pandemic, virtual morning report formats predominated. Compared with traditional in-person reports, virtual report increased attendance, favored resident leadership, and approached a similar range of patient diagnoses with a greater number of case-based presentations and slides. In spite of these characteristics, all programs returned to an in-person format for morning report as pandemic restrictions waned.


Subject(s)
COVID-19 , Teaching Rounds , Humans , COVID-19/epidemiology , Pandemics , Educational Status , Hospitals
14.
Heart Rhythm ; 20(12): 1669-1673, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37591366

ABSTRACT

BACKGROUND: Same-day discharge (SDD) after cardiovascular procedures is rapidly gaining ground. OBJECTIVE: We sought to evaluate the safety of SDD after transvenous lead extraction (TLE). METHODS: We performed a retrospective chart review of patients who underwent elective TLE between January 2020 and October 2021 at our institution. The primary outcome was SDD, and major procedural complications and readmissions within 30 days of the procedure were secondary outcomes. RESULTS: In this analysis of 111 patients who underwent elective TLE, 80 patients (72%) were discharged on the same day (SDD group) while 31 patients (28%) stayed overnight (overnight group). Lead malfunction was the most common indication for TLE in both groups. Patients in the overnight group were more likely to have a lead dwell time of ≤10 years than those in the SDD group (38.7% vs 20% of all leads in each group; P = .042), have laser sheaths used for extraction and a higher number of leads extracted. No major complications were reported in both groups. In a multivariate analysis, lower body mass index and the use of laser sheath during TLE were predictors of overnight stay. Patients who underwent a procedure using advanced extraction techniques were 3.5 times more likely to stay overnight (95% confidence interval 1.27-9.78; P = .016). CONCLUSION: In appropriately selected patients undergoing elective lead extraction, SDD is feasible and safe. Higher body mass index, fewer extracted leads, shorter lead dwell times (<10 years), and less frequent use of laser-powered extraction sheaths were associated with an increased likelihood of SDD.


Subject(s)
Defibrillators, Implantable , Patient Discharge , Humans , Retrospective Studies , Treatment Outcome , Device Removal/adverse effects , Device Removal/methods , Defibrillators, Implantable/adverse effects
15.
Front Neuroinform ; 17: 1207721, 2023.
Article in English | MEDLINE | ID: mdl-37404336

ABSTRACT

Collaborative neuroimaging research is often hindered by technological, policy, administrative, and methodological barriers, despite the abundance of available data. COINSTAC (The Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation) is a platform that successfully tackles these challenges through federated analysis, allowing researchers to analyze datasets without publicly sharing their data. This paper presents a significant enhancement to the COINSTAC platform: COINSTAC Vaults (CVs). CVs are designed to further reduce barriers by hosting standardized, persistent, and highly-available datasets, while seamlessly integrating with COINSTAC's federated analysis capabilities. CVs offer a user-friendly interface for self-service analysis, streamlining collaboration, and eliminating the need for manual coordination with data owners. Importantly, CVs can also be used in conjunction with open data as well, by simply creating a CV hosting the open data one would like to include in the analysis, thus filling an important gap in the data sharing ecosystem. We demonstrate the impact of CVs through several functional and structural neuroimaging studies utilizing federated analysis showcasing their potential to improve the reproducibility of research and increase sample sizes in neuroimaging studies.

16.
Ann Noninvasive Electrocardiol ; 28(5): e13073, 2023 09.
Article in English | MEDLINE | ID: mdl-37515396

ABSTRACT

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.


Subject(s)
Defibrillators, Implantable , Heart Failure , Heart-Assist Devices , Tachycardia, Ventricular , Humans , Heart-Assist Devices/adverse effects , Prospective Studies , Quality of Life , Risk Factors , Electrocardiography , Arrhythmias, Cardiac , Tachycardia, Ventricular/etiology , Treatment Outcome
17.
Methods Mol Biol ; 2671: 307-318, 2023.
Article in English | MEDLINE | ID: mdl-37308652

ABSTRACT

Recent experiments have shown that the molecular complex of vault has large conformational changes at its shoulder and cap regions in solution. From the comparison of two configuration structures, it has been found that the shoulder region can twist and move outward, while the cap region will rotate and push upward correspondingly. To further understand these experimental results, in this paper, we study the vault dynamics for the first time. Since vault has an extremely large-sized structure with around 63,336 Cα atoms, traditional normal mode method with the Cα coarse-grained representation will fall short. We employ a newly invented multiscale virtual particle-based anisotropic network model (MVP-ANM). To reduce the complexity, the 39-folder vault structure is coarse-grained to about 6000 virtual particles, which significantly reduces the computational cost while still maintaining the basic structure information. Among the 14 low frequency eigenmodes from Mode 7 to Mode 20, two eigenmodes, i.e., Mode 9 and Mode 20, are found to be directly associated with the experimental observations. In Mode 9, shoulder region undergoes a significant expansion while the cap part is lifted upward. In Mode 20, a clear rotation of both shoulder and cap regions is well observed. Our results are consistent with the experimental observations. More importantly, these low frequency eigenmodes indicate that the vault waist, shoulder and lower cap regions are the most likely regions for the opening of the vault particle. And the opening mechanism is highly likely to be rotation and expansion at these regions. As far as we know, this is the first work to provide the normal mode analysis for the vault complex.


Subject(s)
Anisotropy , Rotation
19.
Signal Image Video Process ; : 1-8, 2023 Mar 25.
Article in English | MEDLINE | ID: mdl-37362229

ABSTRACT

The Covid-19 pandemic is one of the most significant global health concerns that have emerged in this decade. Intelligent healthcare technology and techniques based on speech signal and artificial intelligence make it feasible to provide a faster and more efficient timely detection of Covid-19. The main objective of our study is to design speech signal-based noninvasive, low-cost, remote diagnosis of Covid-19. In this study, we have developed system to detect Covid-19 from speech signal using Mel frequency magnitude coefficients (MFMC) and machine learning techniques. In order to capture higher-order spectral features, the spectrum is divided into a larger number of subbands with narrower bandwidths as MFMC, which leads to better frequency resolution and less overall noise. As a consequence of an improvement in frequency resolution as well as a decrease in the quantity of noise that is included with the extraction of MFMC, the higher-order MFMCs are able to identify Covid-19 from speech signals with an increased level of accuracy. The procedures for machine learning are often less complicated than those for deep learning, and they may commonly be carried out on regular computers. However, deep learning systems need extensive computing power and data storage. Twelve, twenty-four, thirty, and forty spectral coefficients are obtained using MFMC in our study, and from these coefficients, performance is accessed using machine learning classifiers, such as random forests and K-nearest neighbor (KNN); however, KNN has performed better than the other model with having AUC score of 0.80.

20.
Opt Express ; 31(7): 11431-11446, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37155778

ABSTRACT

We investigate the coexistence of clock synchronization protocols with quantum signals in a common single-mode optical fiber. By measuring optical noise between 1500 nm to 1620 nm we demonstrate a potential for up to 100 quantum, 100 GHz wide channels coexisting with the classical synchronization signals. Both "White Rabbit" and pulsed laser-based synchronization protocols were characterized and compared. We establish a theoretical limit of the fiber link length for coexisting quantum and classical channels. The maximal fiber length is below approximately 100 km for off-the-shelf optical transceivers and can be significantly improved by taking advantage of quantum receivers.

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