bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4140259: Bioresponsive Liposomal Nanoparticle-based Co-Delivery of tPA and DNase I Lyses tPA-Resistant Neutrophil Extracellular-Rich Clots
Authors: Raghunathan Shruti , Disharoon Dante , Hu Keren , Wang Hanyang , Hernandez Selvin , Sen Gupta Anirban 
Published: November 2024

The nonsurgical standard of care for thrombosis is the administration of tPA. However, 40% of occlusive thrombi resist lysis by tPA. These resistant thrombi include both arterial and venous types, particularly those linked to ischemic stroke and deep vein thrombosis. Clot recalcitrance to tPA therapy is largely due to neutrophil extracellular traps (NETs), protein-rich extrusions of DNA that generate in blood clots following neutrophil recruitment and activation. However, the mechanism by which NETs contribute to tPA resistance remains unexplored.
To investigate NET-dependent tPA recalcitrance, we developed several microfluidic models for NET-rich blood clots. In these models, NET-rich blood clots were characterized by a core-shell structure, with NETs most tightly intercalated in the shell, and thicker fibrin colocalized with NETs. Correspondingly, only the shell exhibited significant resistance to tPA therapy in fibrinolysis assays. We observed that neutrophil elastase (NE), the primary enzymatic component of NETs, reduced the efficacy of tPA while DNase I increased its efficacy in the absence of NETs.

Therapeutic concentrations of tPA took 12.3±2.7 min to breach the tPA-resistant shell, which is significantly longer than the
in vivo
half life of tPA (5 minutes). DNase I, an enzyme that degrades NETs, restored tPA efficacy, allowing breach of the shell within 2.5 ± 1.2 min. Building on these findings, we hypothesized that localized co-delivery of tPA and DNase using nanoparticles could remediate clot recalcitrance while minimizing iatrogenic effects and protecting the drugs from degrading in circulation.

We engineered tPA-loaded nanoparticles (tPA-NPs) decorated with a fibrin-targeting peptide, and DNase-loaded nanoparticles (DNase-NPs) decorated with a NE-targeting peptide. A thrombin-cleavable substrate was incorporated into tPA-NPs such that they degraded upon exposure to thrombin, and an NE-cleavable substrate was incorporated into DNase-NPs such that they degraded upon exposure to NE. Upon triggered release, the nanoparticles achieved a concentration of 2 µg/mL tPA and NET-lytic activity equivalent to 50 IU/mL DNase I respectively.
In functional assays, the combination of DNase-NPs and tPA-NPs triggered complete clot dissolution within 12 min (n=4, p<0.05). In conclusion, the functionalized drug delivery system achieved localized co-delivery of tPA and DNase, resulting in complete lysis of clots that are recalcitrant to traditional therapies.
Abstract 4140751: “A silent death: Right heart clot in transit” Acute sub-massive pulmonary embolism
Authors: Udoh Kubiat , POTTABATHINI RAHUL 
Published: November 2024

An 84-year-old male with a history of prostate cancer not on chemotherapy presented to the ED with complaints of shortness of breath worse on exertion ongoing for 1 week accompanied by generalized malaise. On arrival, his troponins were elevated 373, elevated BNP 934. He was requiring supplemental oxygen and an initial bedside cardiac ultrasound was unremarkable. On day 3 of hospitalization, he experienced a syncopal episode and had acute worsening of hypoxemia that prompted a CT angiography of the chest which revealed bilateral, large clot burden pulmonary emboli with proximal thrombus in both the right and left main pulmonary arteries. He was administered a therapeutic dose of low-molecular weight heparin and transferred to the ICU. Despite his large clot burden, there was absence of obstructive shock.
Transthoracic Echocardiogram and bilateral duplex venous ultrasound were obtained to evaluate for right heart strain and clot burden. TTE showed a clot in transit between the right atrium and ventricle, a severely dilated RV with reduced RV systolic function. Extensive clot burden in bilateral lower extremities was visualized on ultrasound. Cardiology was consulted. The risk and benefits of catheter-based aspiration thrombectomy versus thrombolytics (peripheral versus catheter directed) versus surgical thrombectomy versus anticoagulation alone were discussed. Given his high risk of in-hospital mortality, age and frailty, shared-decision making to proceed with anticoagulation alone was decided. Unfortunately, on day 8 of hospitalization, he became bradycardic with no recordable blood pressures, and went into pulseless electrical activity soon after with an eventual demise.
In this clinical case, we discussed sub-massive pulmonary embolism (PE) complicated by a right heart clot-in-transit presenting insidiously. Acute sub-massive pulmonary embolism is defined as intermediate risk PE associated with right ventricular dysfunction without hemodynamic instability. Right heart clot in transit is a rare complication of PE and is associated with a high mortality rate of 20-30%. Anticoagulation is the 1st line treatment for sub-massive PE but definite therapy regarding the management of right heart clot in transit is still debated: CATHETER-BASED INTERVENTION versus SURGICAL THROMBECTOMY as none is thought to be superior. Indication for either therapy centers on hemodynamic compromise which is assessed on a case-by-case basis based on the clinician’s judgement.
Abstract 4141822: Factor VIII replacement therapy in patients with hemophilia undergoing pulsed-field or radiofrequency catheter ablation for atrial fibrillation
Authors: Mohanty Sanghamitra , Compagnucci Paolo , Torlapati PremGeeta , Della Rocca Domenico , La Fazia Vincenzo Mirco , Gianni Carola , MacDonald Bryan , QUINTERO MAYEDO ANGEL , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Di biase Luigi , Casella Michela , Dello Russo Antonio , Natale Andrea 
Published: November 2024

Background:
Typically, hemophilia patients receive up to 6 weeks of intravenous Factor VIII replacement therapy while undergoing radiofrequency ablation (RFA) for atrial fibrillation (AF).

Objective:
We report the management of Factor-VIII replacement therapy in a series of hemophilia patients receiving either pulsed-field (PFA) or RFA.

Methods:
Consecutive hemophilia patients undergoing AF ablation were included in this series. All patients received pulmonary vein isolation (PVI) plus isolation of left atrial posterior wall using either RFA or PFA.

Results:
This series included 8 male patients of which 3 (37.5%) received PFA and 5 underwent RFA for drug-refractory AF. Mean CHA
2
DS
2
-VASc score were 2.67±1.15 and 2.80 ±1.48 (p=0.899) and the HAS-BLED score were 3.33± 1.53 and 2.80±1.10 (p=0.582) in the PFA and the RFA cohorts respectively. Details of pre- and post-procedural Factor VIII replacement therapy is provided in Table 1.

After the procedure, patients undergoing PFA received significantly less Factor VII replacement therapy compared to those receiving RFA (PFA: 78,866.67 ± 1,761.63 vs. RF: 152,260.00 ± 29,704.51 IU, P-value: <0.001). The duration of the replacement therapy was also significantly lower in the PFA patients compared to the RFA cohort (6.65±0.229 vs 31±3.316 days, p<0.001).
No peri-procedural bleeding or thromboembolic events were reported at 1-year follow-up.

Conclusion:
In hemophilia patients undergoing PFA for AF, factor-VIII replacement therapy and oral anticoagulants could be discontinued after one week of the procedure with no bleeding or thromboembolic complications at follow-up, whereas the duration of therapy was significantly longer following RFA.
Abstract 4141921: Hydration to prevent acute kidney injury after pulsed field ablation: importance of timing and fluids amount
Authors: La Fazia Vincenzo Mirco , Mohanty Sanghamitra , Torlapati Prem Geeta , gianni carola , Della Rocca Domenico , Bode Weeranun , Gallinghouse Joseph , Al-Ahmad Amin , Di biase Luigi , Natale Andrea 
Published: November 2024

Previous studies have highlighted the risk of acute kidney injury (AKI) development, underlining the need for strategies to mitigate this complication.
We analyzed 208 consecutive patients who underwent pulsed field ablation (PFA) for post-FDA approval. All patients received pulmonary vein isolation. Ablation of extra-PV sites was performed per the operator’s choice, with no contrast agents . Serum creatinine was measured in all patients at baseline and 24 after ablation.
The aim of our study was to evaluate the impact of hydration timing and the amount of fluids on incidence of AKI in patients undergoing PFA.
Group means for continuous variables were compared using the Student t-test. Categorical variables were compared using the Chi-square test. A ROC analysis was done to evaluate the predictive model of PFA applications to evaluate AKI. All tests were two-tailed and conducted at an α level of 0.05.

We divided patients into two groups:
Group 1
(n=102) received either one liter of saline pre-procedure or one liter pre-procedure followed by a liter post-procedure;
Group 2
(n=106) was preemptively hydrated with two liters of saline before the procedure, followed by additional 500cc if the patient had received more than 100 PF applications. Baseline Characteristics of population are described in
Fig.1a
.

In the comparative analysis of the two groups, there was no significant difference regarding the number of PFA applications administered.
None of the patients in Group 2 experienced AKI, while Group 1 AKI occurred in 9 patients. (0/106 vs 9/102, p-value=0.0034).

The ROC analysis yielded an area under the curve of 0.709 ± 0.107 with a 95% confidence interval ranging from 0.498 to 0.919 (p-value=0.035). An optimal PF application cutoff point of 105.50 was determined, associating a higher probability of AKI with PFA applications exceeding this threshold (sensitivity:0.667, specificity:0.735, Youden's index:0.402) (
Fig.1b
).

Among the 9 patients who developed AKI, we observed that 7 received more than 100PF applications; the remaining 2 patients, each with baseline stage 3 chronic kidney disease and prior episodes of AKI following surgeries, received 54 and 50PF applications, respectively.
In this series of patients, pre-procedural hydration with two liters of fluids eliminated the risk of AKI even in patients who received a high number of PFA applications.
Abstract 4141922: Development of prediction models in heart failure lacks quality: a systematic review
Authors: Bergstedt Seth , Cravero Ellen , Feldewerd Katianna , Walser-Kuntz Evan , Willett Andrew , Stanberry Larissa 
Published: November 2024

Advances in modeling methodology and increased democratization of software led to rapid increase in novel prediction models. In clinical research, these models proclaim novel predictors, promise superior accuracy and meaningful improvements in patient outcomes. Developing an accurate prediction model requires rigorous methodology with great attention to study design and conduct. Failure to adhere leads to prediction bias and may result in harmful decisions.
We conducted a systematic review of research articles in heart failure listed in PubMed 2018 – 2023 and presented by their authors as developing prediction models, either diagnostic or prognostic. The study variables were selected based on PROBAST and TRIPOD (Table 1). These were summarized and the study conducts were evaluated against the gold standard of prediction modeling per PROBAST and TRIPOD. For each study, we calculated the optimal sample size, i.e. the minimal size required for at least 5% prediction accuracy and 90% shrinkage in parameters. Sentiment analysis was performed to estimate the prevalence of promotional language in the abstract corpus.
From 6,429 studies, 212 studies were presented as developing prediction models. Of those, 83 (39%) were truly about developing prediction models (TPM) and the rest were impostors, i.e. inferential models misrepresented as predictive.
Mostly, TPMs were prognostic, modeled binary outcomes, and employed machine-learning methods (Table 1). Commonly, essential data volume summaries were lacking and handling of missing data was inadequate. The deficit in the number of samples in model training was 1499 (-316, 3866) samples with 52(71%) studies below the optimal size.
Model validation or testing was not performed in 30% of the studies. Discrimination statistics were reported often in testing but not in validation. The calibration was rarely assessed at either phase. Thirty (36%) studies had enough information to implement risk score calculations. The sentiment analysis showed increased use of hype words in both TPMs and impostors relative to 2020-rates in Millar et al (2022).
Most TPM studies exhibit poor design, insufficient sample size, mishandling of missing data, and inadequate model evaluation. These deficiencies result in biased risk estimates, degrade the performance in external data limiting generalizability and clinical utility of the developed models. Excessive use of hype can be misleading and may impede objective evaluation by the readers.
Abstract 4142012: Ectasias of Multiple Coronary Arteries and a Coronary Cameral Fistula Between Right Coronary Artery and Coronary Sinus
Authors: Sung Shijun , Gray Hannah 
Published: November 2024

Case Description:
A 59-year-old male with history of hypertension, diabetes, Hashimoto’s thyroiditis presented with new, progressive shortness of breath. No murmur or extra heart sound were heard, and the lung sounds were normal. Exam was notable for significant lower extremity edema.

Echocardiography showed reduced LVEF of 30%, and cardiac catheterization found hemodynamically significant shunt with Qp:Qs of 1.47:1. Coronary angiography revealed a tortuous and extremely aneurysmal RCA, as well as multivessel coronary artery disease (mvCAD) involving LAD, D1, LCx, OM1. Notably, the LAD had multiple aneurysmal segments and areas of eccentric stenosis upto 90%.
Multislice CT angiography further characterized the RCA, which extends to the coronary sinus (CS) distally forming a coronary cameral fistula (CCF). Cardiac MRI did not show significant ischemic findings.
The patient received medical therapy consisting of antiplatelet agents, high dose statin, beta blocker and ACE inhibitor, as well as diuretics. Patient underwent surgical closure of fistula and a 2-vessel coronary artery bypass graft surgery, with a LIMA pedicle graft to the LAD, and SV graft to the LCx.
Postoperatively, patient was continued on medical therapy with improvement of symptoms. At the time of discharge, LV systolic function improved to 39% and there were no findings concerning for coronary artery thrombosis or fistula repair failure. Patient was planned to gradually start cardiac rehab.

Discussion:
CCF is a rare anomalous connection between coronary arteries and a cardiac chamber or other major blood vessels of the heart. CCF can be congenital or acquired and has many variations. It is often clinically silent. However some patients can develop heart failure, angina, and arrhythmia due to significant intracardiac shunt or coronary steal phenomenon. In this case presentation, it is likely that his heart failure was caused by the significant left to right shunt due to the fistula. He had concomitant ischemic cardiomyopathy in the setting of severe mvCAD, however the notable ectasia of LAD suggests there is a underlying disease that also affected RCA, leading to formation of the CCF.

In addition to diagnostic coronary angiogram, advances in noninvasive cardiac imaging allow further identification and characterization of these fistulae. Surgical approach was appropriate in this patient given the findings complex mvCAD and the CCF with significant hemodynamic shunt.
Abstract 4142070: Single Ventricle Palliation Pathways: Patient Characteristics and Outcomes
Authors: Kuntz Michael , Staffa Steven , Valencia Eleonore , Nasr Viviane 
Published: November 2024

Introduction:
The choice between conventional surgical (SP) and hybrid (HP) stage 1 palliation for single ventricle heart disease remains debated. Pulmonary artery banding and prostaglandins followed by delayed surgical stage 1 (DSP) remains another option. HP is proposed for high-risk patients. We aimed to describe index hospitalization outcomes for patients undergoing these 3 pathways. We hypothesized that patients undergoing HP and DSP have more comorbid conditions, higher morbidity, and longer length of stay (LOS).

Methods:
Using the Pediatric Health Information System data, January 2016 – August 2023, we analyzed the characteristics and index hospitalization outcomes for patients with single ventricle disease undergoing SP, HP, and DSP.

Results:
Our final cohort included 1,872 patients (1,573 SP; 176 HP; 123 DSP). Prematurity was most common (45.5%) in the DSP compared to the HP (27.8%) and SP (9.5%) groups (P<0.001); the rate of small for gestational age birth (SGA, <2.5 kg) was similarly distributed. Non-cardiac comorbidities were most prevalent in DSP (neurologic, gastrointestinal, need home technology) and HP (respiratory). LOS (days) was highest for DSP (median 130, IQR:69–195) compared to HP (median 61, IQR:37–139) and SP (median 45, IQR:29–80)(P<0.001). Disposition varied (P<0.001), with in-hospital mortality highest among HP (25.6%) compared to DSP (13.8%) and SP (11.3%); the rate of index hospitalization heart transplant was 8.5% for HP, DSP 0.8%, and SP 0.9%.

Among patients born prematurely or SGA, LOS was longest for DSP (median 143, IQR:88–216) followed by HP (median 72, IQR:52–139) and SP (median 59, IQR:36–124)(P<0.001). Disposition also varied (P=0.004), with higher in-hospital mortality among HP (35.9%) compared to DSP (16.9%) and SP (19.9%); transplant was highest among HP (4.7%) compared to DSP (0%) and SP (0.8%).
Adjusted total costs per hospital day did not vary significantly.

Conclusions:
Patients undergoing DSP and HP are more often premature or SGA. Patients undergoing HP are most likely to have index hospitalization mortality or transplant. While recognizing the limitations of administrative databases, our data does describe the current utilization trend and outcomes for SP, HP, and DSP.
Abstract 4142090: Venous Access Alone
vs.
Arterial and Venous Access for Patent Arterial Duct Device Closure in Childhood
Authors: Hassan Ahmed , Chaturvedi Rajiv , Benson Lee 
Published: November 2024

Background:
The persistently patent arterial duct accounts for ~12% of congenital heart lesions. Untreated, it may result in heart failure due to volume loading of the left heart, pulmonary hypertension, and infective endarteritis. Percutaneous device closure is the preferred occlusion technique, with the standard approach consisting of femoral artery access for angiography and venous access for device delivery (AA). A venous-only strategy (VA) for angiography and device delivery can also be employed.

Hypothesis:
We hypothesized that VA would eliminate arterial complications, and reduce procedure times and radiation exposure compared to standard AA.

Methods:
This retrospective cohort study reviewed isolated arterial duct device closures at the Hospital for Sick Children from January 1, 2011 through December 31, 2022. Exclusions included premature neonates, children requiring arterial access for monitoring and those who underwent other procedures. Children were categorized based upon initial access determined by operator preference, into VA or AA groups.

Results:
The cohort consisted of 405 children, 252 (62.2%) females, with a median age of 3.1 years (IQR1.30–5.84), median weight 13.2kg (IQR 9.0–19.5), and duct diameter of 2.9mm (IQR 2.0–3.5) with no significant differences between the groups. Type A ducts were more frequent in the AA group (90% vs. 72%). The VA group included 106 children, of which 14 (13.2%) required AA conversion for angiography due to complex anatomy, to assess device positon prior to release, but remained in the VA group for analysis.

Children in the VA group had lower dose area product (DAP) (p<0.001), fluoroscopy times (p=0.025), contrast volumes (p<0.001), procedure times (p<0.001), and recovery room lengths of stay (LOS) (p<0.001). Six (5.7%) VA children required admission compared to 44 (14.7%) in the AA group (p=0.015) with no difference in reintervention rates.
Weighted regression analysis showed VA was associated with reduced admission likelihood (OR: 0.354 [0.131,0.822], p=0.024), DAP (coef -126.4 [-213.3,-39.4], p=0.004) and contrast volumes (coef 31.2 [-36.6,-25.9], p<0.001) compared to AA.

Conclusions:
Venous only access was associated with lower DAP and recovery room LOS. Additionally, VA was associated with a lower likelihood of admission with no difference in reintervention rates, suggesting procedural safety. These findings support the consideration of VA as a preferred approach for appropriate cases.
Abstract 4142098: Clinical Link of Neutrophilia to Neovascularization and Fibrinolysis
Authors: Eton MD FACS DFSVS Darwin 
Published: November 2024

The anti-angiogenic impact of neutrophil elastase clouded the understanding of the role of neutrophils in promoting neovascularization (NV) and fibrinolysis in patients with chronic limb-threatening ischemia (CLTI). The impact of significant neutrophilia was not studied during clinical trials using Granulocyte Colony Stimulating Factor (G-CSF) to boost the deficient circulating endothelial progenitor cell count. Only recently have activated human neutrophils been documented to release pro-angiogenic factors such as VEGFA, Hepatocyte Growth Factor (HGF), MMP-9, angiopoietin (Ang1). They also stimulate and modulate fibrinolysis through release of proteases, and by promoting endothelial cell release of plasmin.
The purpose of this abstract is to link clinical evidence* to these observations. Proteomic and cytometry data were obtained in 14 CLTI patients treated with Filgrastim 7-10 mcg/kg SQ every 72 h for up to a month. The absolute neutrophil count (ANC) increased a mean of 6-fold a day after each injection, returning to baseline within 72 hours. Significant (p < 0.05) increases in the concentration of VEGFA, HGF, MMP-9, Ang1 was measured by ELISA a day after both the 5th and the 10th Filgrastim doses as compared to baseline. The ANC peak was measured at the same time, as well as was the significant (p < 0.01) increases in the plasma concentration of plasmin (>10-fold) and Fibrin Degradation Products (FDP) (>5-fold). Since these patients also wore an infra-geniculate programmed compression pump (PCP) for 3 hours daily, these data were compared to 19 CLTI patients treated with PCP alone. PCP was used to improve the ischemic micro-environment and to provide endothelial shear stress as a strategy to induce arteriogenesis. PCP use did not influence the concentration of any of these proteins and did not induce neutrophilia. Resolution of ischemic rest pain and healing of ischemic ulcers contributed to limb salvage. Arterial hemodynamic improvement was supported by angiographic evidence of NV (enlarged corkscrew collaterals, improved contrast transit through the ischemic tissue). Segmental arterial recanalization indicated fibrinolysis. No hemorrhage occurred over the 30 day course. A prospective investigation of the uncovered link between neutrophilia, NV, and fibrinolysis is justified. * J Tissue Eng Regen Med. 2022 May;16(5):496-510. doi: 10.1002/term.3284