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1.
Resusc Plus ; 19: 100712, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39113756

ABSTRACT

Aims: To describe and explore predictors of bystander defibrillation in Ireland during the period 2012 to 2020. To examine the relationship between bystander defibrillation and health system developments. Methods: National level Out of Hospital Cardiac Arrest (OHCA) registry data were interrogated, focusing on patients who had defibrillation performed. Bystander defibrillation (as compared to EMS initiated defibrillation) was the key outcome of concern. Logistic regression models were built and refined by fitting predictors, performing stepwise variable selection and by adding pairwise interactions that improved fit. Results: The data included 5,751 cases of OHCA where defibrillation was performed. Increasing year over time (OR 1.17, 95% CI 1.13, 1.21) was associated with increased adjusted odds of bystander defibrillation. Non-cardiac aetiology was associated with reduced adjusted odds of bystander defibrillation (OR 0.30, 95% CI 0.21, 0.42), as were increasing age in years (OR 0.99, 95% CI 0.987, 0.996) and night-time occurrence of OHCA (OR 0.67, 95% CI 0.53, 0.83). Six further variables in the final model (sex, call response interval, incident location (home or other), who witnessed collapse (bystander or not witnessed), urban or rural location, and the COVID period) were involved in significant interactions. Bystander defibrillation was in general less likely in urban settings and at home locations. Whilst women were less likely to receive bystander defibrillation overall, in witnessed OHCAs, occurring outside the home, in urban areas and outside of the COVID-19 period women were more likely, to receive bystander defibrillation. Conclusions: Defibrillation by bystanders has increased incrementally over time in Ireland. Interventions to address sex and age-based disparities, alongside interventions to increase bystander defibrillation at night, in urban settings and at home locations are required.

2.
Article in English | MEDLINE | ID: mdl-39099302

ABSTRACT

BACKGROUND: Guidelines recommend defibrillation testing (DFT) during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. Implant position, patient characteristics and device factors, such as shock impedance, influence defibrillation success. To evaluate the shock impedance, a manual synchronous 10J shock (low energy synchronous shock [LESS]) can be delivered, without the need to induce ventricular fibrillation (VF). OBJECTIVE: To compare LESS and DFT impedance values and to evaluate the diagnostic accuracy of LESS impedance for predicting a successful DFT during S-ICD implantation. METHODS: Consecutive S-ICD implantations were included. Shock impedances were compared by paired t-tests. Univariate analysis was performed to investigate factors associated with successful DFT. A prediction model of successful DFT based on LESS impedance was assessed by logistic regression. Receiver operating characteristic (ROC) curve, area under the ROC curve and the Hosmer-Lemeshow tests were used to evaluate the accuracy of LESS impedance. RESULTS: Sixty patients were included (52 ± 14 years; 69% male). LESS and DFT impedance values were highly correlated (r2 = 0.97, p < .01). Patients with a failed first shock had higher body mass index (BMI) (30 ± 3 vs. 25.7 ± 4.3, p = .014), higher mean LESS (120 ± 35Ω vs. 86. ± 23Ω, p = .0013) and DFT impedance (122 ± 33Ω vs. 87 ± 24Ω, p = .0013). ROC analysis showed that LESS impedance had a good diagnostic performance in predicting a successful conversion test (AUC 84% [95% CI: 0.72-0.92]) with a cutoff value of <94Ω to identify a successful DFT (sensitivity 71%, specificity 73%). CONCLUSION: LESS impedance values without the need to induce VF can intraoperatively predict a successful DFT.

3.
Heart Rhythm ; 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39103135

ABSTRACT

BACKGROUND: The PRAETORIAN score is developed as an alternative for defibrillation testing (DFT) post subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, and assess three aspects of implant position on a bidirectional chest X-ray. The score is validated on a standard standing chest X-ray with arms elevated in the lateral view. OBJECTIVE: We aim to evaluate the effect of different anatomical positions on the PRAETORIAN score. METHODS: Thirty S-ICD patients underwent standard posterior-anterior (PA) and lateral chest X-rays, including additional lateral views in two positions: standing with arms down and supine with arms alongside the body. PRAETORIAN score and weighted kappa coefficient were calculated for each position. RESULTS: In 8 out of 30 patients the PRAETORIAN score was ≥90 in standard position. The agreement in PRAETORIAN score was substantial (κ=0.677) for the position with the arms down and fair (κ =0.399) for the supine position. In 10 patients (33%) with the arms down the PRAETORIAN score decreased, of whom 4 changed to a lower risk category. In 16 patients (53%) the PRAETORIAN score decreased in supine position, of whom 7 changed to a lower risk category of which one patient changed from high to low risk. CONCLUSION: A supine or arms-down position during chest X-rays can result in lower PRAETORIAN scores and underestimation of associated risk on DFT failure. This emphasizes the importance of correct anatomical positioning ('arms up') during chest X-rays when using the PRAETORIAN score.

4.
Am J Emerg Med ; 84: 149-157, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39127020

ABSTRACT

AIM: The aim of this study was to summarize the existing evidence about the effectiveness of double defibrillation (DD) in comparison to standard defibrillation for patients with refractory ventricular fibrillation (RVF). DD encompasses double "sequential" external defibrillation (DSeq-D) and double "simultaneous" defibrillation (DSim-D), with the study also shedding light on the respective effects of DSeq-D and DSim-D. METHODS: Investigators systematically searched PubMed, EMBASE and Cochrane Central databases for randomized controlled trials (RCTs) and cohort studies from their inception until June 06, 2024. The rate of survival to hospital discharge was the primary outcome, while the incidence of return of spontaneous circulation (ROSC), termination of ventricular fibrillation (VF), survival to hospital admission and good neurologic outcome were secondary outcomes. Relative ratios (RR) and 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity was assessed using I square value. RESULTS: A total of 6 trials, comprising 1360 patients, were included. One was an RCT, and five were observational cohort studies. The RCT showed that, compared to standard defibrillation, DSeq-D was associated with higher incidences of survival to hospital discharge, termination of VF, ROSC and good neurologic outcome. However, the pooled results of cohort studies found no benefit of DD over standard defibrillation in survival to hospital discharge (RR, 0.91; 95% CI, 0.46-1.78), nor in secondary outcomes. Furthermore, subgroup analysis suggested DSim-D was linked with lower ROSC rate compared to standard defibrillation (RR, 0.65; 95% CI, 0.49-0.86), while there was no significance between DSeq-D and standard defibrillation (RR, 1.00; 95% CI, 0.70-1.42). CONCLUSIONS: The benefit of DSeq-D in survival to hospital discharge for RVF patients was found in the RCT, but not in cohort studies. Additionally, DSim-D should be applied with greater caution for RVF patients. Further validation is needed through larger-scale and higher-quality trials. TRIAL REGISTRY: INPLASY; Registration number: INPLASY202340015; URL: https://inplasy.com/.

7.
JACC Adv ; 3(7): 101033, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39130039

ABSTRACT

Background: Defibrillation in the critical first minutes of out-of-hospital cardiac arrest (OHCA) can significantly improve survival. However, timely access to automated external defibrillators (AEDs) remains a barrier. Objectives: The authors estimated the impact of a statewide program for drone-delivered AEDs in North Carolina integrated into emergency medical service and first responder (FR) response for OHCA. Methods: Using Cardiac Arrest Registry to Enhance Survival registry data, we included 28,292 OHCA patients ≥18 years of age between 1 January 2013 and 31 December 2019 in 48 North Carolina counties. We estimated the improvement in response times (time from 9-1-1 call to AED arrival) achieved by 2 sequential interventions: 1) AEDs for all FRs; and 2) optimized placement of drones to maximize 5-minute AED arrival within each county. Interventions were evaluated with logistic regression models to estimate changes in initial shockable rhythm and survival. Results: Historical county-level median response times were 8.0 minutes (IQR: 7.0-9.0 minutes) with 16.5% of OHCAs having AED arrival times of <5 minutes (IQR: 11.2%-24.3%). Providing all FRs with AEDs improved median response to 7.0 minutes (IQR: 6.2-7.8 minutes) and increased OHCAs with <5-minute AED arrival to 22.3% (IQR: 16.4%-30.9%). Further incorporating optimized drone networks (326 drones across all 48 counties) improved median response to 4.8 minutes (IQR: 4.3-5.2 minutes) and OHCAs with <5-minute AED arrival to 56.3% (IQR: 46.9%-64.2%). Survival rates were estimated to increase by 34% for witnessed OHCAs with estimated drone arrival <5 minutes and ahead of FR and emergency medical service. Conclusions: Deployment of AEDs by FRs and optimized drone delivery can improve AED arrival times which may lead to improved clinical outcomes. Implementation studies are needed.

10.
Prehosp Emerg Care ; : 1-13, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39140885

ABSTRACT

OBJECTIVES: Early defibrillation with an automated external defibrillator (AED) can effectively improve the survival rate of patients with out-of-hospital cardiac arrest (OHCA). Placing AEDs in public locations can reduce the defibrillation response interval from collapse to defibrillation. Most public AEDs are currently placed in a stationary way (S-AED) with limited coverage area. Bus mounted AED (B-AED) can be delivered directly to the demand point. Although B-AEDs are only available during bus operating hours, they provide greater coverage area. When the number of available AEDs is insufficient, better coverage may be achieved by placing a portion of AEDs as B-AEDs. Our purpose is developing a model to determine the optimal locations of B-AEDs and S-AEDs with a predetermined number of available AEDs. The goal is to maximize the total coverage level of all demand points. METHODS: We proposed a joint location model to place B-AEDs and S-AEDs based on the p-median problem (JPMP). Using data from Chang'an District, Xi'an City, China, we determined the optimal AED deployment. The performance of JPMP was compared with several other models. The coverage results of JPMP are analyzed in details, including the quantity assignment, coverage level, and geographical location of B-AEDs and S-AEDs. The impact of the bus departure intervals on coverage was also discussed. RESULTS: The use of B-AEDs results in an average 98.43% increase in the number of covered demand points, and an average 74.05% increase in total coverage level. In optimal AED deployment, B-AEDs coverage follows an inverted U-shaped curve with increasing number of available AEDs. It begins to decrease when all demand points during the operating hours are covered. With a constant number of available AEDs, the total coverage level increases and then decreases as the bus departure interval increases. The larger the number of available AEDs, the smaller the optimal departure interval. CONCLUSIONS: With a given number of available AEDs, combinational deployment of B-AEDs and S-AEDs significantly improves the coverage level. B-AEDs are recommended when AEDs are insufficient. If more AEDs are available, better coverage can be obtained with reasonable location of S-AEDs and B-AEDs.

11.
Am Heart J ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39084483

ABSTRACT

Out-of-hospital cardiac arrest (OHCA) occurs in nearly 350,000 people each year in the United States (US). Despite advances in pre- and in-hospital care, OHCA survival remains low and is highly variable across systems and regions. The critical barrier to improving cardiac arrest outcomes is not a lack of knowledge about effective interventions, but rather the widespread lack of systems of care to deliver interventions known to be successful. The RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial is a 7-year pragmatic, cluster-randomized trial of 60 counties (57 clusters) in North Carolina using an established registry and is testing whether implementation of a customized set of strategically targeted community-based interventions improves survival to hospital discharge with good neurologic function in OHCA relative to control/standard care. The multi-faceted intervention comprises rapid cardiac arrest recognition and systematic bystander CPR instructions by 9-1-1 telecommunicators, comprehensive community CPR training and enhanced early automated external defibrillator (AED) use prior to emergency medical systems (EMS) arrival. Approximately 20,000 patients are expected to be enrolled in the RACE CARS Trial over 4 years of the assessment period. The primary endpoint is survival to hospital discharge with good neurologic outcome defined as a cerebral performance category (CPC) of 1 or 2. Secondary outcomes include the rate of bystander CPR, defibrillation prior to arrival of EMS, and quality of life. We aim to identify successful community- and systems-based strategies to improve outcomes of OHCA using a cluster randomized-controlled trial design that aims to provide a high level of evidence for future application.

12.
Front Netw Physiol ; 4: 1401661, 2024.
Article in English | MEDLINE | ID: mdl-39022296

ABSTRACT

Current treatments of cardiac arrhythmias like ventricular fibrillation involve the application of a high-energy electric shock, that induces significant electrical currents in the myocardium and therefore involves severe side effects like possible tissue damage and post-traumatic stress. Using numerical simulations on four different models of 2D excitable media, this study demonstrates that low energy pulses applied shortly after local minima in the mean value of the transmembrane potential provide high success rates. We evaluate the performance of this approach for ten initial conditions of each model, ten spatially different stimuli, and different shock amplitudes. The investigated models of 2D excitable media cover a broad range of dominant frequencies and number of phase singularities, which demonstrates, that our findings are not limited to a specific kind of model or parameterization of it. Thus, we propose a method that incorporates the dynamics of the underlying system, even during pacing, and solely relies on a scalar observable, which is easily measurable in numerical simulations.

14.
Comput Methods Programs Biomed ; 253: 108239, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823116

ABSTRACT

BACKGROUND: The excitable gap (EG), defined as the excitable tissue between two subsequent wavefronts of depolarization, is critical for maintaining reentry that underlies deadly ventricular arrhythmias. EG in the His-Purkinje Network (HPN) plays an important role in the maintenance of electrical wave reentry that underlies these arrhythmias. OBJECTIVE: To determine if rapid His bundle pacing (HBP) during reentry reduces the amount of EG in the HPN and ventricular myocardium to suppress reentry maintenance and/or improve defibrillation efficacy. METHODS: In a virtual human biventricular model, reentry was initiated with rapid line pacing followed by HBP delivered for 3, 6, or 9 s at pacing cycle lengths (PCLs) ranging from 10 to 300 ms (n=30). EG was calculated independently for the HPN and myocardium over each PCL. Defibrillation efficacy was assessed for each PCL by stimulating myocardial surface EG with delays ranging from 0.25 to 9 s (increments of 0.25 s, n=36) after the start of HBP. Defibrillation was successful if reentry terminated within 1 s after EG stimulation. This defibrillation protocol was repeated without HBP. To test the approach under different pathological conditions, all protocols were repeated in the model with right (RBBB) or left (LBBB) bundle branch block. RESULTS: Compared to without pacing, HBP for >3 seconds reduced average EG in the HPN and myocardium across a broad range of PCLs for the default, RBBB, and LBBB models. HBP >6 seconds terminated reentrant arrhythmia by converting HPN activation to a sinus rhythm behavior in the default (6/30 PCLs) and RBBB (7/30 PCLs) models. Myocardial EG stimulation during HBP increased the number of successful defibrillation attempts by 3%-19% for 30/30 PCLs in the default model, 3%-6% for 14/30 PCLs in the RBBB model, and 3%-11% for 27/30 PCLs in the LBBB model. CONCLUSION: HBP can reduce the amount of excitable gap and suppress reentry maintenance in the HPN and myocardium. HBP can also improve the efficacy of low-energy defibrillation approaches targeting excitable myocardium. HBP during reentrant arrhythmias is a promising anti-arrhythmic and defibrillation strategy.


Subject(s)
Bundle of His , Humans , Bundle of His/physiopathology , Arrhythmias, Cardiac/therapy , Cardiac Pacing, Artificial/methods , Electric Countershock/methods , Heart Ventricles/physiopathology , Models, Cardiovascular
15.
Resuscitation ; 201: 110286, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38901663

ABSTRACT

OBJECTIVE: Optimal timing for subsequent defibrillation attempts for Out-of-hospital cardiac arrest (OHCA) patients with recurrent VF/pVT is uncertain. We investigated the relationship between VF/pVT duration and return of spontaneous circulation (ROSC) in OHCA patients with recurrent shockable rhythms. METHODS: We analyzed data from the Salt Lake City Fire Department (SLCFD) spanning from 2012 to 2023. The implementation of rhythm-filtering technology since 2011 enabled real-time rhythm interpretation during CPR, with local protocols allowing early defibrillation for recurrent/refractory VF/pVT cases. We included patients experiencing four or five episodes of VF and pVT rhythms and employed generalized estimating equation (GEE) regression analysis to examine the association between VF/pVT durations preceding recurrent defibrillation and return of spontaneous circulation (ROSC). RESULTS: Analysis of 622 appropriate shocks showed that patients achieving ROSC had significantly shorter median VF/pVT duration than those who did not achieve ROSC (0.83 minutes vs. 1.2 minutes, p = 0.004). Adjusted analysis of those with 4 VF/pVT episodes (N = 142) revealed that longer VF/pVT durations were associated with lower odds of achieving ROSC (odds ratio: 0.81, 95% CI: 0.72-0.93, p = 0.005). Every one-minute delay in intra-arrest defibrillation is predicted to decrease the likelihood of achieving ROSC by 19%. CONCLUSION: Every one-minute increase in intra-arrest VF/pVT duration was associated with a statistically significant 19% decrease in the chance of achieving ROSC. This highlights the importance of reducing time to shock in managing recurrent VF/pVT. The findings suggest reevaluating the current recommendations of two minutes intervals for rhythm check and shock delivery.


Subject(s)
Cardiopulmonary Resuscitation , Electric Countershock , Out-of-Hospital Cardiac Arrest , Return of Spontaneous Circulation , Time-to-Treatment , Humans , Out-of-Hospital Cardiac Arrest/therapy , Electric Countershock/methods , Electric Countershock/statistics & numerical data , Male , Female , Middle Aged , Aged , Cardiopulmonary Resuscitation/methods , Ventricular Fibrillation/therapy , Ventricular Fibrillation/complications , Ventricular Fibrillation/physiopathology , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/physiopathology , Time Factors , Retrospective Studies , Recurrence
16.
Heart Rhythm ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38762820

ABSTRACT

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

17.
Resusc Plus ; 18: 100651, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38711911

ABSTRACT

Aim: The optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. Methods: Between 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. Results: At 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5-12) vs 11 (7-16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4-6 min. Conclusion: A longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

19.
Resuscitation ; 198: 110200, 2024 May.
Article in English | MEDLINE | ID: mdl-38582444

ABSTRACT

BACKGROUND: Annually 15,200 children suffer an in-hospital cardiac arrest (IHCA) in the US. Ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) is the initial rhythm in 10-15% of these arrests. We sought to evaluate the association of number of shocks and early dose escalation with survival for initial VF/pVT in pediatric IHCA. METHODS: Using 2000-2020 data from the American Heart Association's (AHA) Get with the Guidelines®-Resuscitation (GWTG-R) registry, we identified children >48 hours of life and ≤18 years who had an IHCA from initial VF/pVT and received defibrillation. RESULTS: There were 251 subjects (37.7%) who received a single shock and 415 subjects (62.3%) who received multiple shocks. Baseline and cardiac arrest characteristics did not differ between those who received a single shock versus multiple shocks except for duration of arrest and calendar year. The median first shock dose was consistent with AHA dosing recommendations and not different between those who received a single shock versus multiple shocks. Survival was improved for those who received a single shock compared to multiple shocks. However, no difference in survival was noted between those who received 2, 3, or ≥4 shocks. Of those receiving multiple shocks, no difference was observed with early dose escalation. CONCLUSIONS: In pediatric IHCA, most patients with initial VF/pVT require more than one shock. No distinctions in patient or pre-arrest characteristics were identified between those who received a single shock versus multiple shocks. Subjects who received a single shock were more likely to survive to hospital discharge even after adjusting for duration of resuscitation.


Subject(s)
Cardiopulmonary Resuscitation , Electric Countershock , Heart Arrest , Registries , Tachycardia, Ventricular , Ventricular Fibrillation , Humans , Male , Female , Child , Electric Countershock/methods , Electric Countershock/statistics & numerical data , Heart Arrest/therapy , Heart Arrest/mortality , Heart Arrest/complications , Child, Preschool , Tachycardia, Ventricular/therapy , Tachycardia, Ventricular/mortality , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/epidemiology , Adolescent , Ventricular Fibrillation/complications , Ventricular Fibrillation/therapy , Ventricular Fibrillation/mortality , Cardiopulmonary Resuscitation/methods , Cardiopulmonary Resuscitation/statistics & numerical data , Infant , United States/epidemiology
20.
Biotechnol Biofuels Bioprod ; 17(1): 56, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654330

ABSTRACT

BACKGROUND: Microbial expansins (EXLXs) are non-lytic proteins homologous to plant expansins involved in plant cell wall formation. Due to their non-lytic cell wall loosening properties and potential to disaggregate cellulosic structures, there is considerable interest in exploring the ability of microbial expansins (EXLX) to assist the processing of cellulosic biomass for broader biotechnological applications. Herein, EXLXs with different modular structure and from diverse phylogenetic origin were compared in terms of ability to bind cellulosic, xylosic, and chitinous substrates, to structurally modify cellulosic fibrils, and to boost enzymatic deconstruction of hardwood pulp. RESULTS: Five heterogeneously produced EXLXs (Clavibacter michiganensis; CmiEXLX2, Dickeya aquatica; DaqEXLX1, Xanthomonas sacchari; XsaEXLX1, Nothophytophthora sp.; NspEXLX1 and Phytophthora cactorum; PcaEXLX1) were shown to bind xylan and hardwood pulp at pH 5.5 and CmiEXLX2 (harboring a family-2 carbohydrate-binding module) also bound well to crystalline cellulose. Small-angle X-ray scattering revealed a 20-25% increase in interfibrillar distance between neighboring cellulose microfibrils following treatment with CmiEXLX2, DaqEXLX1, or NspEXLX1. Correspondingly, combining xylanase with CmiEXLX2 and DaqEXLX1 increased product yield from hardwood pulp by ~ 25%, while supplementing the TrAA9A LPMO from Trichoderma reesei with CmiEXLX2, DaqEXLX1, and NspEXLX1 increased total product yield by over 35%. CONCLUSION: This direct comparison of diverse EXLXs revealed consistent impacts on interfibrillar spacing of cellulose microfibers and performance of carbohydrate-active enzymes predicted to act on fiber surfaces. These findings uncover new possibilities to employ EXLXs in the creation of value-added materials from cellulosic biomass.

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