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INTRODUCTION: Much clinical evidence has shown that right ventricular (RV) apical pacing is detrimental to left ventricular function. Preservation of the use of the His-Purkinje (H-P) system may be ideal in heart block that is restricted to the AV node, but may be of no benefit when H-P disease exists. AIM: To investigate the feasibility of direct His-bundle pacing (DHBP) using a new system consisting of a steerable catheter and a new 4.1 F screw-in lead. METHOD: Between May and December 2004, 26 patients (19 male, mean age: 77 +/- 5 years) with a standard pacemaker (PM) indication and preserved His-bundle conduction were enrolled and DHBP was attempted. RESULTS: DHBP was achieved in 24 patients (92%); two patients were paced in the His area, but the paced QRS morphology and duration were different from the native QRS. The mean time for lead positioning was 19 +/- 17 minutes, the mean fluoroscopy time was 11 +/- 8 minutes, and the total procedure time (skin-to-skin including positioning of a quadripolar diagnostic catheter for His recording) was 75 +/- 18 minutes. In DHBP pacing, the acute pacing threshold was 2.3 +/- 1.0 V at a pulse duration of 0.5 msec, and the sensed potentials were 2.9 +/- 2.0 mV. At a 3-month follow-up examination, the same QRS duration and morphology recorded on implantation were observed in all patients. The pacing threshold was 2.8 +/- 1.4 V, and sensed potentials were 2.5 +/- 1.8 mV; the sensing configuration was changed from bipolar to unipolar in 6 patients to resolve undersensing issues. No major complications were observed. CONCLUSIONS: This feasibility study shows that DHBP can be accomplished with a new system consisting of a steerable catheter and an active fixation lead in 92% of the patients in whom it was attempted. [ABSTRACT FROM AUTHOR]

Purpose: To compare the aberrometric profile of the Artisan Aphakia lens (Opthec BV) and transscleral plug FIL-SSF lens (Soleko) and to assess the impact of tilt and decentration on their optical performance., Methods: This retrospective observational study was conducted at Azienda Ospedaliera Universitaria Careggi, Florence, Italy, with a consecutive cohort of aphakic eyes undergoing secondary lens implantation with an Artisan or FIL-SSF lens. Wavefront analysis was performed using a pyramidal wavefront-based aberrometer (Osiris-T; CSO). Tilt and decentration were calculated using anterior segment optical coherence tomography (MS-39; CSO)., Results: The study included 47 eyes from 45 patients: 24 eyes in the FIL-SSF group and 23 eyes in the Artisan group. Decentration was 0.39 ± 0.14 mm in the FIL-SSF group and 0.51 ± 0.16 mm in the Artisan group ( P = .02). The mean tilt value was 6.6 ± 2.35 degrees in the FIL-SSF group and 5.9 ± 1.86 degrees in the Artisan group ( P = .13). Internal higher order aberrations (HOAs) were 0.23 ± 0.07 μm in the FIL-SSF group and 0.29 ± 0.13 μm in the Artisan group ( P = .02). The point spread function (PSF) Strehl ratio was 0.12 ± 0.05 in the FIL-SSF group and 0.10 ± 0.04 ( P = .11) in the Artisan group. The PSF Strehl ratio without lower order aberration (PSFw2) was 0.28 ± 0.12 in the FIL-SSF group and 0.23 ± 0.09 in the Artisan group ( P = .01)., Conclusions: The Artisan and FIL-SSF lenses provide comparable optical performance in terms of the PSF Strehl ratio. However, the Artisan lens appears to be more susceptible to decentration, which may result in increased higher order aberrations and a consequently lower PSFw2 Strehl ratio. [ J Refract Surg . 2024;40(12):e926-e933.] ., Competing Interests: Disclosure: The authors have disclosed no potential conflicts of interest, financial or otherwise.

Chronic lymphocytic leukemia (CLL) is characterized by an extremely variable clinical course. Although several parameters have been shown to be associated with clinical outcomes in patients with CLL, there remains substantial intragroup clinical heterogeneity in otherwise molecularly and staging homogeneous CLL subgroups. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course and that higher CAT expression is associated with the presence of the rs1001179 single nucleotide polymorphism (SNP) T allele in the CAT promoter. Herein, we genotyped CLL patients for CAT rs1001179 SNP in an exploratory study (n = 235) and in a sequential independent validation study (n = 531). Time-to-event modeling analyses for time-to-first-treatment (TTFT) from the two patients' cohorts showed that TT genotype was associated with a shorter TTFT, independently of other currently used prognostic parameters in CLL. Moreover, the TT genotype identifies CLL patients with a faster clinical progression even within subgroups of patients with low-risk biological and clinical hallmarks. In conclusion, our data show that the TT genotype identifies CLL patients with a shorter TTFT, pointing to this SNP as a possible prognostic factor, which can improve patients' risk stratification leading to better patient management and personalized therapeutic choices., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

The growing awareness of tricuspid regurgitation (TR) and the fast-expanding array of devices aiming to percutaneously repair or replace the tricuspid valve have underscored the central role of multi-modality imaging in comprehensively assessing the anatomical and functional characteristics of TR. Accurate phenotyping of TR, the right heart, and pulmonary vasculature via echocardiography, computed tomography, and, occasionally, cardiovascular magnetic resonance and right heart catheterization is deemed crucial in choosing the most suitable treatment strategy for each patient and achieving procedural success. In the first part of the present review, key imaging factors for patient selection will be discussed. In the ensuing sections, an overview of the most commonly used, commercially available systems for transcatheter repair/replacement will be presented, along with their respective selection criteria and information on intraprocedural imaging guidance; these are edge-to-edge repair, orthotopic and heterotopic replacement, and valve-in-valve procedures.

Background: Few certainties exist regarding optimal management of Blood Pressure (BP) in the very first hours after an ischemic stroke and many questions remain still unanswered. Our work aimed to evaluate the role of BP and its trend as possible determinants of in-hospital mortality (primary outcome), discharge disabilities and hospitalization length (secondary outcomes) in ischemic stroke patients presented with Hypertensive Emergencies (HE)., Methods: We retrospectively evaluated patients presented to Niguarda Hospital, Emergency Department (ED), from 2015 to 2017 with a neurological ischemic HE. BP at ED presentation (T0), its management in ED (T1) and its values at the stroke unit admission (T2) were evaluated., Results: 267 patients were included (0.13 % of all ED accesses and 17.9 % of all ischemic strokes). In the whole population, BP values were not associated with in-hospital mortality while T0 and T2 SBP result were associated to discharge disability and hospitalization length. In pre-specified subgroup analysis these associations were confirmed only in untreated subjects (not anti-hypertensive nor thrombolysis). In fact, no significant relationship can be found between BP values and any secondary outcome in thrombolysis and anti-hypertensive treated patients., Conclusions: BP values and its management can not be related to in-hospital mortality in stroke patients, presented with HE, while they are associated to discharge disability and hospitalization length. In subgroup analysis, results were confirmed only in untreated (not anti-hypertensive therapies nor thrombolytic)., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL., (© 2024. The Author(s).)

Myocardial contusion is a rare and potentially fatal complication of chest trauma. There is no unique definition for this entity: some authors define myocardial contusion as a mild increase in cardiac biomarkers in the context of chest trauma, while for others the diagnosis requires evidence of pathologic findings at cardiac imaging. Consequently, the real incidence of myocardial contusion remains unknown, varying in reports between 8% and 71%. We describe a case of cardiac contusion secondary to a low-energy blunt chest trauma, manifesting as persistent ST-elevation associated with elevation of myocardial necrosis markers, with consequent myocardial stunning of the right ventricular free wall. As there is no consensus regarding the diagnostic pathway, it is essential to integrate first-level exams (ECG and laboratory findings) with cardiac magnetic resonance imaging, to define the presence of cardiac contusion and its extent, particularly if the echocardiographic data are unconclusive.

Aims: The mortality risk of patients with moderate aortic stenosis is not well known, but recent studies suggested that it might negatively affect prognosis. We aimed to assess the natural history and clinical burden of moderate aortic stenosis and to investigate the interaction of patients' baseline characteristics with prognosis., Methods: Systematic research was conducted on PubMed. The inclusion criteria were inclusion of patients with moderate aortic stenosis; and report of the survival at 1-year follow-up (minimum). Incidence ratios related to all-cause mortality in patients and controls of each study were estimated and then pooled using a fixed effects model. All patients with mild aortic stenosis or without aortic stenosis were considered controls. Meta-regression analysis was performed to assess the impact of left ventricular ejection fraction and age on the prognosis of patients with moderate aortic stenosis., Results: Fifteen studies and 11 596 patients with moderate aortic stenosis were included. All-cause mortality was significantly higher among patients with moderate aortic stenosis than in controls in all timeframes analysed (all P  < 0.0001). Left ventricular ejection fraction and sex did not significantly impact on the prognosis of patients with moderate aortic stenosis ( P  = 0.4584 and P  = 0.5792), while increasing age showed a significant interaction with mortality (estimate = 0.0067; 95% confidence interval: 0.0007-0.0127; P  = 0.0323)., Conclusion: Moderate aortic stenosis is associated with reduced survival. Further studies are necessary to confirm the prognostic impact of this valvulopathy and the possible benefit of aortic valve replacement., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Intraprocedural stroke is a well-documented and feared potential risk of cardiovascular transcatheter procedures (TPs). Moreover, subclinical neurological events or covert central nervous system infarctions are concerns related to the development of dementia, future stroke, cognitive decline, and increased risk of mortality. Cerebral protection devices (CPDs) were developed to mitigate the risk of cardioembolic embolism during TPs. They are mechanical barriers designed to cover the ostium of the supra-aortic branches in the aortic arch, but newer devices are able to protect the descending aorta. CPDs have been mainly designed and tested to provide cerebral protection during transcatheter aortic valve replacement (TAVR), but their use in both Catheterization and Electrophysiology laboratories is rapidly increasing. CPDs have allowed us to perform procedures that were previously contraindicated due to high thromboembolic risk, such as in cases of intracardiac thrombosis identified at preprocedural assessment. However, several concerns related to their employment have to be defined. The selection of patients at high risk of thromboembolism is still a subjective choice of each center. The aim of this review is to update the evidence on the use of CPDs in either Cath labs or EP labs, providing an overview of their structural characteristics. Future perspectives focusing on their possible future employment are also discussed.

Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)-Lp(a)-lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.

Background Malnutrition is associated with poor prognosis in several cardiovascular diseases. However, its prognostic impact in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER) is not well known. This study sought to assess the prevalence, clinical associations, and prognostic consequences of malnutrition in patients undergoing TEER. Methods and Results A total of 892 patients undergoing TEER from the international MIVNUT (Mitral Valve Repair and Nutritional Status) registry were studied. Malnutrition status was assessed with the Controlling Nutritional Status score. The association of nutritional status with mortality was analyzed with multivariable Cox regression models, whereas the association with heart failure admission was assessed by Fine-Gray models, with death as a competing risk. According to the Controlling Nutritional Status score, 74.4% of patients with TEER had any degree of malnutrition at the time of TEER (75.1% in patients with body mass index <25 kg/m 2 , 72.1% in those with body mass index ≥25 kg/m 2 ). However, only 20% had moderate-severe malnutrition. TEER was successful in most of patients (94.2%). During a median follow-up of 1.6 years (interquartile range, 0.6-3.0), 267 (29.9%) patients died and 256 patients (28.7%) were admitted for heart failure after TEER. Compared with normal nutritional status moderate-severe malnutrition resulted a strong predictor of mortality (adjusted hazard ratio [HR], 2.1 [95% CI, 1.1-2.4]; P <0.001) and heart failure admission (adjusted subdistribution HR, 1.6 [95% CI, 1.1-2.4]; P =0.015). Conclusions Malnutrition is common among patients submitted to TEER, and moderate-severe malnutrition is strongly associated with increased mortality and heart failure readmission. Assessment of nutritional status in these patients may help to improve risk stratification.

Polyhydrides are a novel class of superconducting materials with extremely high critical parameters, which is very promising for sensor applications. On the other hand, a complete experimental study of the best so far known superconductor, lanthanum superhydride LaH 10 , encounters a serious complication because of the large upper critical magnetic field H C2 (0), exceeding 120-160 T. It is found that partial replacement of La atoms by magnetic Nd atoms results in significant suppression of superconductivity in LaH 10 : each at% of Nd causes a decrease in T C by 10-11 K, helping to control the critical parameters of this compound. Strong pulsed magnetic fields up to 68 T are used to study the Hall effect, magnetoresistance, and the magnetic phase diagram of ternary metal polyhydrides for the first time. Surprisingly, (La,Nd)H 10 demonstrates completely linear H C2 (T) ∝ |T - T C |, which calls into question the applicability of the Werthamer-Helfand-Hohenberg model for polyhydrides. The suppression of superconductivity in LaH 10 by magnetic Nd atoms and the robustness of T C with respect to nonmagnetic impurities (e.g., Y, Al, C) under Anderson's theorem gives new experimental evidence of the isotropic (s-wave) character of conventional electron-phonon pairing in lanthanum decahydride., (© 2022 Wiley-VCH GmbH.)

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an extremely variable clinical course. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course. Elucidating mechanisms regulating CAT expression in CLL is preeminent to understand disease mechanisms and develop strategies for improving its clinical management. In this study, we investigated the role of the CAT promoter rs1001179 single nucleotide polymorphism (SNP) and of the CpG Island II methylation encompassing this SNP in the regulation of CAT expression in CLL. Leukemic cells harboring the rs1001179 SNP T allele exhibited a significantly higher CAT expression compared with cells bearing the CC genotype. CAT promoter harboring the T -but not C- allele was accessible to ETS-1 and GR-β transcription factors. Moreover, CLL cells exhibited lower methylation levels than normal B cells, in line with the higher CAT mRNA and protein expressed by CLL in comparison with normal B cells. Methylation levels at specific CpG sites negatively correlated with CAT levels in CLL cells. Inhibition of methyltransferase activity induced a significant increase in CAT levels, thus functionally validating the role of CpG methylation in regulating CAT expression in CLL. Finally, the CT/TT genotypes were associated with lower methylation and higher CAT levels, suggesting that the rs1001179 T allele and CpG methylation may interact in regulating CAT expression in CLL. This study identifies genetic and epigenetic mechanisms underlying differential expression of CAT, which could be of crucial relevance for the development of therapies targeting redox regulatory pathways in CLL., (© 2022. The Author(s).)

Recently, several research groups announced reaching the point of metallization of hydrogen above 400 GPa. Despite notable progress, detecting superconductivity in compressed hydrogen remains an unsolved problem. Following the mainstream of extensive investigations of compressed metal polyhydrides, here small doping of molecular hydrogen by strontium is demonstrated to lead to a dramatic reduction in the metallization pressure to ≈200 GPa. Studying the high-pressure chemistry of the Sr-H system, the formation of several new phases is observed: C2/m-Sr 3 H 13 , pseudocubic SrH 6 , SrH 9 with cubic F 4 ¯ 3 m $F\bar{4}3m$ -Sr sublattice, and pseudo tetragonal superionic P1-SrH 22 , the metal hydride with the highest hydrogen content (96 at%) discovered so far. High diffusion coefficients of hydrogen in the latter phase D H  = 0.2-2.1 × 10 -9 m 2 s -1 indicate an amorphous state of the H-sublattice, whereas the strontium sublattice remains solid. Unlike Ca and Y, strontium forms molecular semiconducting polyhydrides, whereas calcium and yttrium polyhydrides are high-T C superconductors with an atomic H sublattice. The discovered SrH 22 , a kind of hydrogen sponge, opens a new class of materials with ultrahigh content of hydrogen., (© 2022 Wiley-VCH GmbH.)

Several signaling pathways are aberrantly activated in T-ALL due to genetic alterations of their components and in response to external microenvironmental cues. To functionally characterize elements of the signaling network in T-ALL, here we analyzed ten signaling proteins that are frequently altered in T-ALL -namely Akt, Erk1/2, JNK, Lck, NF-κB p65, p38, STAT3, STAT5, ZAP70, Rb- in Jurkat, CEM and MOLT4 cell lines, using phospho-specific flow cytometry. Phosphorylation statuses of signaling proteins were measured in the basal condition or under modulation with H 2 O 2 , PMA, CXCL12 or IL7. Signaling profiles are characterized by a high variability across the analyzed T-ALL cell lines. Hierarchical clustering analysis documents that higher intrinsic phosphorylation of Erk1/2, Lck, ZAP70, and Akt, together with ZAP70 phosphorylation induced by H 2 O 2 , identifies Jurkat cells. In contrast, CEM are characterized by higher intrinsic phosphorylation of JNK and Rb and higher responsiveness of Akt to external stimuli. MOLT4 cells are characterized by higher basal STAT3 phosphorylation. These data document that phospho-specific flow cytometry reveals a high variability in intrinsic as well as modulated signaling networks across different T-ALL cell lines. Characterizing signaling network profiles across individual leukemia could provide the basis to identify molecular targets for personalized T-ALL therapy.