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Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA). Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab 4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit). The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female) were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS) pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP), numbers of swollen or tender joints, or Disease Activity Score (DAS) 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

BACKGROUND: Multidisciplinary heart team (HT) evaluation is recommended for patients with severe primary mitral regurgitation to optimize treatment decisions. However, its impact on patient outcomes remains unknown. We evaluated the impact of implementing mitral HT on patient survival. METHODS AND RESULTS: We conducted a retrospective cohort study of patients with new diagnoses of severe primary mitral regurgitation in a large healthcare network echocardiogram database between 2016 and 2020. We compared the incidence of multidisciplinary evaluation by structural cardiology and cardiac surgery services and 2-year survival before and after mitral HT implementation. The 1:1 propensity-score matching between pre- and post-mitral HT used Society of Thoracic Surgeons Predicted Risk of Mortality for mitral repair, age, sex, race, heart failure symptoms, inpatient setting, history of MI, and dementia as covariates. Logistic regression identified variables associated with the likelihood of undergoing multidisciplinary evaluation. Among 70 510 echocardiograms performed, 391 patients had severe primary mitral regurgitation (median age, 77 years; 46% women). Multidisciplinary evaluation increased from 29% to 89% (P

Abstract An advance has been made towards a method for forecasting earthquakes several months before they occur. The method relies on changes of groundwater chemistry as earthquake precursors. In a study published in 2014, we showed that changes of groundwater chemistry occurred prior to and were associated with two earthquakes of magnitude 5 and higher, which affected northern Iceland in 2012 and 2013. Here we test the hypothesis that similar or larger earthquakes could have been forecast in the following decade (i.e. 2014–2023) based on our published findings. We found that we could have forecast one of the three greater than magnitude 5 earthquakes that occurred. Noting that changes of groundwater chemistry were oscillatory, we infer expansion and contraction of the groundwater source region caused by coupled crustal dilation and fracture mineralisation associated with the stress build-up before earthquakes. We conclude by proposing how our approach could be implemented elsewhere.

Abstract Volcanoes in extensional environments may show gradual subsidence over decades during quiescent periods, due to various processes such as magma withdrawal, cooling, contraction, plate spreading and viscoelastic response. If significant rheological anomalies reside in volcano roots, due to the presence of magma and hot rock, they can influence the style of deformation. We use Finite Element Method (FEM) models to explore how strain localization due to extension can lead to volcano deflation. We apply rheological models comprising an elastic layer overlying a viscoelastic domain and include local up‐doming regions of low viscosity material beneath volcanic centers. The models reveal a localized subsidence above the rheological anomaly, influenced by the tectonic extension, and by the up‐doming volume and its viscosity. The models suggest that plate divergence may account for 4–5 mm/yr of observed subsidence at Krafla and Askja volcanic systems (KVS and AVS, respectively) in North Iceland.

Objective: Ischemic mitral regurgitation is prevalent and associated with high surgical risk. With the less-invasive option of transcatheter edge-to-edge repair, the optimal patient selection for mitral valve operation for ischemic mitral regurgitation remains unclear. We sought to identify high-risk features in this group to guide patient selection. Methods: Using the Cardiothoracic Surgery Trial Network's severe ischemic mitral regurgitation trial data, we identified patient and echocardiographic characteristics associated with an increased risk of 2-year mortality using the support vector classifier and Cox proportional hazards model. We identified 6 high-risk features associated with 2-year survival. Patients were categorized into 3 groups, each having 1 or less, 2, or 3 or more of the 6 identified high-risk features. Results: Among the 251 patients, the median age was 69 (Q1 62, Q3 75) years, and 96 (38%) were female. Two-year mortality was 21% (n = 53). We identified 6 high-risk preoperative features: age 75 years or more (n = 69, 28%), prior sternotomy (n = 49, 20%), renal insufficiency (n = 69, 28%), gastrointestinal bleeding (n = 15, 6%), left ventricular ejection fraction less than 40% (n = 131, 52%), and ventricular end-systolic volume index less than 50 mL/m2 (n = 93, 37%). In patients who had 1 or less, 2, and 3 or more high-risk features, 90-day mortality was 4.2% (n = 5), 9.9% (n = 4), and 20.0% (n = 10), respectively (P = .006), and 2-year mortality was 10% (n = 12), 22% (n = 18), and 46% (n = 23) (P

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Abstract Grabens, or valleys formed during extensional tectonic events, are common but rarely observed during formation. In November 2023, inelastic surface deformation formed abruptly along Iceland's plate boundary in Grindavík. We documented graben formation in real‐time through satellite mapping (InSAR), seismicity, GNSS data, repeated lidar surveys, and field mapping. Five normal faults and ∼12 fissures ruptured the surface delineating two grabens separated by a horst, a context not present in other contemporary case studies. The graben normal faults slipped rapidly (over hours) and maximum surface motions coincided with the occurrence of turbulent seismic swarms in both space and time. Although 3 eruptions took place ∼15 km northeast of Grindavík from 2021 to 2023, attributed to magma intrusions (i.e., dikes), none of these also formed grabens. Thus, the Grindavík grabens shows evidence for tectonic origins. Real‐time monitoring of these phenomena provide insight into graben formation on Earth and potentially on other planets.

Background Gender‐ and sex‐based disparities in mitral valve disease exist; however the factors associated with these differences are unknown. Identifying these differences is essential in devising mitigating strategies. We evaluated gender and sex differences among patients with severe primary mitral regurgitation (MR) across treatment phases. Methods and Results We conducted a retrospective cohort study of patients with new diagnoses of severe primary MR between 2016 and 2020. We compared multidisciplinary evaluation incidence and 2‐year survival between men and women. We analyzed a subgroup meeting class 1 indications for intervention, which includes severe symptomatic MR or severe asymptomatic MR with ejection fraction 40 mm. Logistic regression models identified predictors associated with the likelihood of multidisciplinary evaluation. Among 330 patients meeting class 1 indications, women were older (79 versus 76 years, P=0.01) and had higher Society of Thoracic Surgeons risk scores for mitral valve repair than men (2.5% versus 1.4%, P=0.003). Women were less likely to undergo multidisciplinary evaluation (57% versus 84%, P

Abstract To investigate the association between area deprivation index (ADI) and aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Patients aged 40–95 years with severe AS confirmed by echocardiography were included. The 9-digit zip code of patient residence address was used to identify the ADI ranking, based on which patients were divided into 5 groups (with Group E being most deprived). The rates of AV intervention were compared among 5 groups using competing risks analysis, with death as a competing event. We included 1751 patients with severe AS from 2013 to 2018 followed for a median 2.8 (interquartile range, 1.5–4.8) years. The more distressed ADI groups tended to be younger (P = 0.002), female (P

Background Multidisciplinary heart team (HT) evaluation is recommended for patients with severe primary mitral regurgitation to optimize treatment decisions. However, its impact on patient outcomes remains unknown. We evaluated the impact of implementing mitral HT on patient survival. Methods and Results We conducted a retrospective cohort study of patients with new diagnoses of severe primary mitral regurgitation in a large healthcare network echocardiogram database between 2016 and 2020. We compared the incidence of multidisciplinary evaluation by structural cardiology and cardiac surgery services and 2‐year survival before and after mitral HT implementation. The 1:1 propensity‐score matching between pre‐ and post‐mitral HT used Society of Thoracic Surgeons Predicted Risk of Mortality for mitral repair, age, sex, race, heart failure symptoms, inpatient setting, history of MI, and dementia as covariates. Logistic regression identified variables associated with the likelihood of undergoing multidisciplinary evaluation. Among 70 510 echocardiograms performed, 391 patients had severe primary mitral regurgitation (median age, 77 years; 46% women). Multidisciplinary evaluation increased from 29% to 89% (P

Objective: Liver disease (LD) is considered a risk factor for inferior outcomes in general and cardiac surgery, yet current cardiac surgery risk estimators exclude LD, and literature on the topic remains scant. We sought to evaluate whether the presence of advanced LD is associated with inferior outcomes following cardiac surgery. Methods: This single-center, retrospective, observational study included 285 patients diagnosed with LD who underwent cardiac surgery in 2010 to 2020. The cohort contained 3 groups, Child-Turcotte-Pugh (CTP) class A (n = 219), CTP early-class B (n = 34), and CTP advanced-class B (n = 32). A model for end-stage liver disease score of 12.7 points (determined using a receiver-operating characteristic curve analysis on 30-day mortality) dichotomized class B into early- and advanced-groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of 30-day mortality. Results: Patients in CTP advanced-class B had the longest length of stay (14 days), highest incidence of prolonged ventilation (46.9%), renal failure (21.9%), 30-day mortality (18.8%), and in-hospital mortality (18.8%). Incidence of ≥1 postoperative complication was higher in CTP advanced-class B (59.4%), compared with CTP class A (37.9%) and CTP early-class B (38.2%). Multivariate logistic regression analysis demonstrated that female sex (odds ratio, 3.01; 95% CI, 1.07-8.77; P = .037) and peripheral vascular disease (odds ratio, 4.01; 95% CI, 1.33-12.2; P = .013) were independent predictors of 30-day mortality in patients with advanced LD. Conclusions: Severity of LD influences perioperative outcomes following cardiac surgery. Our data suggest that patients in CTP class A and selected patients in CTP class B (model for end-stage liver disease score

Objective: Tricuspid annuloplasty is associated with increased risk of atrioventricular block and subsequent implantation of a permanent pacemaker. However, the exact incidence of permanent pacemaker, associated risk factors, and outcomes in this frame remain debated. The aim of the study was to report permanent pacemaker incidence, risk factors, and outcomes after tricuspid annuloplasty from nationwide databases. Methods: By using data from multiple Swedish mandatory national registries, all patients (n = 1502) who underwent tricuspid annuloplasty in Sweden from 2006 to 2020 were identified. Patients who needed permanent pacemaker within 30 days from surgery were compared with those who did not. The cumulative incidence of permanent pacemaker implantation was estimated. A multivariable logistic regression model was fit to identify risk factors of 30-day permanent pacemaker implantation. The association between permanent pacemaker implantation and long-term survival was evaluated with multivariable Cox regression. Results: The 30-day permanent pacemaker rate was 14.2% (214/1502). Patients with permanent pacemakers were older (69.8 ± 10.3 years vs 67.5 ± 12.4 years, P = .012). Independent risk factors of permanent pacemaker implantation were concomitant mitral valve surgery (odds ratio, 2.07; 95% CI, 1.34-3.27), ablation surgery (odds ratio, 1.59; 95% CI, 1.12-2.23), and surgery performed in a low-volume center (odds ratio, 1.85; 95% CI, 1.17-2.83). Permanent pacemaker implantation was not associated with increased long-term mortality risk (adjusted hazard ratio, 0.74; 95% CI, 0.53-1.03). Conclusions: This nationwide study demonstrated a high risk of permanent pacemaker implantation within 30 days of tricuspid annuloplasty. However, patients who needed a permanent pacemaker did not have worse long-term survival, and the cumulative incidence of heart failure and major adverse cardiovascular events was similar to patients who did not receive a permanent pacemaker.

BACKGROUND: Guidelines provide class I recommendations for aortic valve intervention for patients with symptomatic severe aortic stenosis (AS) or reduced ejection fraction, but the cornerstone of management for asymptomatic patients has been watchful waiting. This is based on historical nonrandomized data, but randomized controlled trials (RCTs) have now been performed of early surgical aortic valve replacement (SAVR) for asymptomatic severe AS. We performed a meta-analysis of RCTs comparing early SAVR to watchful waiting for asymptomatic severe AS, focusing on individual end points of death and heart failure (HF) hospitalization. METHODS: We systematically identified all RCTs comparing early SAVR to watchful waiting in patients with asymptomatic severe AS and synthesized the data in a random-effects meta-analysis. The prespecified primary end point was all-cause mortality. RESULTS: Two trials randomizing 302 patients were included. Early SAVR lead to a 55% reduction in all-cause mortality (hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P = .014). There was no heterogeneity (I2 = 0.0%). Early SAVR also lead to a 79% reduction in HF hospitalization (hazard ratio, 0.21; 95% confidence interval, 0.05-0.96; P = .044). CONCLUSIONS: In patients with severe asymptomatic AS and normal ejection fraction, early SAVR reduces death and HF hospitalization compared to initial conservative management. This challenges current treatment standards and has implications for the clinical care of these patients and for guidelines.

Abstract Unrest began in July 2021 at Askja volcano in the Northern Volcanic Zone (NVZ) of Iceland. Its most recent eruption, in 1961, was predominantly effusive and produced ∼0.1 km3 lava field. The last plinian eruption at Askja occurred in 1875. Geodetic measurements between 1983 and 2021 detail subsidence of Askja, decaying in an exponential manner. At the end of July 2021, inflation was detected at Askja volcano, from GNSS observations and Sentinel‐1 interferograms. The inflationary episode can be divided into two periods from the onset of inflation until September 2023. An initial period until 20 September 2021 when geodetic models suggest transfer of magma (or magmatic fluids) from within the shallowest part of the magmatic system (comprising an inflating and deflating source), potentially involving silicic magma. A following period when one source of pressure increase at shallow depth can explain the observations.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Abstract Internalization of complement membrane attack complexes (MACs) assembles NLRP3 inflammasomes in endothelial cells (EC) and promotes IL-β-mediated tissue inflammation. Informed by proteomics analyses of FACS-sorted inflammasomes, we identify a protein complex modulating inflammasome activity on endosomes. ZFVYE21, a Rab5 effector, partners with Rubicon and RNF34, forming a “ZRR” complex that is stabilized in a Rab5- and ZFYVE21-dependent manner on early endosomes. There, Rubicon competitively disrupts inhibitory associations between caspase-1 and its pseudosubstrate, Flightless I (FliI), while RNF34 ubiquitinylates and degradatively removes FliI from the signaling endosome. The concerted actions of the ZRR complex increase pools of endosome-associated caspase-1 available for activation. The ZRR complex is assembled in human tissues, its associated signaling responses occur in three mouse models in vivo, and the ZRR complex promotes inflammation in a skin model of chronic rejection. The ZRR signaling complex reflects a potential therapeutic target for attenuating inflammasome-mediated tissue injury.

Objective Evidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi.Methods Data from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were pooled. We investigated the association of sex with treatment response using logistic regression. The primary outcome was clinically important improvement (CII) at 6 months according to Ankylosing Spondylitis Disease Activity Score with C-reactive protein (CRP) (≥1.1 decrease). We adjusted for age, country and TNFi start year. A secondary outcome was retention rates over 24 months of follow-up assessed by Kaplan-Meier estimator.Results In total, 6451 axSpA patients with data on CII were assessed for treatment response; 2538 (39%) were women and 3913 (61%) were men. Women presented at baseline with lower CRP levels but had higher scores on patient-reported outcome measures. At 6 months, 53% of the women and 66% of the men had CII. Women had a lower relative risk of CII compared with men (0.81; 95% CI 0.77 to 0.84). This sex difference was similar in adjusted analysis (0.85; 95% CI 0.82 to 0.88). Retention rates were evaluated in 27 702 patients. The TNFi 6/12/24 months retention rates were significantly lower among women (79%/66%/53%) than men (88%/79%/69%).Conclusion Treatment response and retention rates are lower among women with axSpA initiating their first TNFi. Sex differences in treatment effectiveness were present regardless of the outcome measure used for treatment response, and differences in retention rates transpired early and increased as time progressed.