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An abstract of the study "TDI Is an Useful Tool to Detect the Severity of Left Ventricular Asynchrony and Its Prognostic Value in Patients with Left Bundle Branch Block and Dilated Cardiomyopath," by C. Volponi and F. Fedele, is presented.

Introduction: Lesion size index (LSI) was introduced with the use of Tacticath™ and as a surrogate of lesion quality. The metric used to achieve the predetermined values involves combined information of contact force (CF), power and radiofrequency time. Rapid atrial pacing (RAP) and high-frequency low-tidal volume ventilation (HFLTV) independently or in combination improve catheter stability and CF and quality of lesions. Data of the impact of body weight adjusted HFLTV ventilation strategy associated with RAP in the lesion metrics still lacking. The study aimed to compare the results of high-power short-duration (HPSD) atrial fibrillation ablation using simultaneous weight adjusted HFLTV and RAP and standard ventilation (SV) protocol., Methods: Prospective, nonrandomized study with 136 patients undergoing de novo ablation divided into two groups; 70 in RAP (100 ppm) + HFLTV with 4 mL/kg of tidal volume and 25 breaths/min (group A) and 66 patients with SV in intrinsic sinus rhythm (group B). Ablation using 50 W, CF of 5-10 g/10-20 g and 40 mL/minute flow rate on the posterior and anterior left atrial wall, respectively., Results: No procedure-related complications. Group A: Mean LSI points 70 ± 16.5, mean total lower LSI 3.4 ± 0.5, mean total higher LSI 8.2 ± 0.4 and mean total LSI 5.6 ± 0.6. Anterior and posterior wall mean total LSI was 6.0 ± 0.4 and 4.2 ± 0.3, respectively. Mean local impedance drop (LID) points were 118.8 ± 28.4, mean LID index (%) 12.9 ± 1.5, and mean LID < 12% points 55.9 ± 23.8. Anterior and posterior wall mean total LID index were 13.6 ± 2.0 and 11.9 ± 1.7, respectively. Recurrence in 11 (15.7%) patients. Group B: Mean LSI points 56 ± 2.7, mean total lower LSI 2.9 ± 0.7, mean total higher LSI 6.9 ± 0.9, and mean total LSI 4.8 ± 0.8. Anterior and posterior wall mean total LSI was 5.1 ± 0.3 and 3.5 ± 0.5, respectively. Mean LID points were 111.4 ± 21.5, mean LID index (%) 11.4 ± 1.2, and mean LID < 12% points 54.9 ± 25.2. Anterior and posterior wall mean total LID index were 11.8 ± 1.9 and 10.3 ± 1.7, respectively. Recurrence in 14 (21.2%) patients. Mean follow up was 15.2 ± 4.4 months., Conclusion: Weight adjusted HFLTV ventilation with RAP HPSD ablation produced lower recurrence rate and better LSI and LID parameters in comparison to SV and intrinsic sinus rhythm., (© 2024 Wiley Periodicals LLC.)

Cross-presentation by type 1 DCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels of bona-fide neoantigens (neoAgs) remain unclear. Here we develop a hypermutated model of non-small cell lung cancer in female mice, encoding genuine MHC-I neoepitopes to study neoAgs-specific CD8 T cell responses in spontaneous settings and upon Flt3L + αCD40 (DC-therapy). We find that cDC1 are required to generate broad CD8 responses against a range of diverse neoAgs. DC-therapy promotes immunogenicity of weaker neoAgs and strongly inhibits the growth of high tumor-mutational burden (TMB) tumors. In contrast, low TMB tumors respond poorly to DC-therapy, generating mild CD8 T cell responses that are not sufficient to block progression. scRNA transcriptional analysis, immune profiling and functional assays unveil the changes induced by DC-therapy in lung tissues, which comprise accumulation of cDC1 with increased immunostimulatory properties and less exhausted effector CD8 T cells. We conclude that boosting cDC1 activity is critical to broaden the diversity of anti-tumoral CD8 T cell responses and to leverage neoAgs content for therapeutic advantage., (© 2024. The Author(s).)

Liver cancer represents the fourth leading cause of cancer-associated death worldwide. The heterogeneity of its tumor microenvironment (TME) is a major contributing factor of metastasis, relapse, and drug resistance. Regrettably, late diagnosis makes most liver cancer patients ineligible for surgery, and the frequent failure of non-surgical therapeutic options orientates clinical research to the investigation of new drugs. In this context, cellular senescence has been recently shown to play a pivotal role in the progression of chronic inflammatory liver diseases, ultimately leading to cancer. Moreover, the stem-like state triggered by senescence has been associated with the emergence of drug-resistant, aggressive tumor clones. In recent years, an increasing number of studies have emerged to investigate senescence-associated hepatocarcinogenesis and its derived therapies, leading to promising results. In this review, we intend to provide an overview of the recent evidence that unveils the role of cellular senescence in the most frequent forms of primary and metastatic liver cancer, focusing on the involvement of this mechanism in therapy resistance.

Background: Better contact force (CF) and catheter stability (CS) during atrial fibrillation (AF) ablation are associated with higher success rate. Changes in CF and CS are observed during respiratory movements and cardiac contraction. Previous studies have suggested that rapid atrial pacing (RAP) and high-frequency, low-tidal-volume ventilation (HFLTV) independently or in combination improve CS and CF and quality of lesions. Data from a body weight-adjusted HFLTV strategy associated with RAP in AF high-power, short-duration (HPSD) ablation are still lacking., Objective: This study aimed to compare the results of HPSD AF ablation using simultaneous weight-adjusted HFLTV and RAP and standard ventilation (SV) protocol., Methods: This was a prospective, nonrandomized study with 136 patients undergoing de novo ablation were divided into 2 groups: 70 in RAP (100 ppm) + HFLTV with 4 mL/kg of tidal volume and 25 breaths/min (group A) and 66 patients with SV in intrinsic sinus rhythm (group B). The ablation used 50 W, CF of 5 to 10 g and 10 to 20 g, and 40 mL/min flow rate on the posterior and anterior left atrial walls, respectively., Results: There were no procedure-related complications. In group A, left atrial and total ablation times were 53.5 ± 8.3 minutes and 67.4 ± 10.1 minutes, respectively. Radiofrequency time was 19.7 ± 5.7 minutes, radioscopy time was 3.4 ± 1.8 minutes, 62 (88.6%) patients had first-pass isolation, 23 (33.3%) patients had elevation of luminal esophageal temperature, and 7 (10%) patients had recurrence. In group B, left atrial time was 56.7 ± 10.8 minutes, total ablation time was 72.4 ± 11.5 minutes, radiofrequency time was 22.4 ± 6.2 minutes, radioscopy time was 3.6 ± 3 minutes, 58 (87.9%) patients had first-pass isolation, and 20 (30.3%) patients had luminal esophageal temperature elevation., Conclusion: Weight-adjusted HFLTV with RAP in comparison with SV and intrinsic sinus rhythm in HPSD ablation is safe with no CO 2 retention. The approach produced significantly reduced radiofrequency, left atrial, and total ablation times and better CF and local impedance drop indexes., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

HCC, the most prevalent form of primary liver cancer, is prototypically an inflammation-driven cancer developing after years of inflammatory insults. Consequently, the hepatic microenvironment is a site of complex immunological activities. Moreover, the tolerogenic nature of the liver can act as a barrier to anti-tumor immunity, fostering cancer progression and resistance to immunotherapies based on immune checkpoint inhibitors (ICB). In addition to being a site of primary carcinogenesis, many cancer types have high tropism for the liver, and patients diagnosed with liver metastasis have a dismal prognosis. Therefore, understanding the immunological networks characterizing the tumor microenvironment (TME) of HCC will deepen our understanding of liver immunity, and it will underpin the dominant mechanisms controlling both spontaneous and therapy-induced anti-tumor immune responses. Herein, we discuss the contributions of the cellular and molecular components of the liver immune contexture during HCC onset and progression by underscoring how the balance between antagonistic immune responses can recast the properties of the TME and the response to ICB.

Lombroso and Fejerman, in 1977, described non-epileptic movements in normal infants and named them "benign myoclonus of early infancy", which were recently relabelled by Fernandez-Alvarez as "benign polymorphous movement disorder of infancy" (BPMDI). The focus of our study was to describe, categorize and point out the peculiar clinical representations of these heterogeneous phenomena through our video footage, particularly to those less experienced in paediatric neurology. We included all infants with a video-EEG performed at our unit or a home video recording of "Fejerman-Lombroso", "benign myoclonus of early infancy", "shuddering attacks" or "paroxysmal non-epileptic movements". Twenty-one children were selected. Age at onset ranged between two and 13 months, age at disappearance ranged between seven and 16 months, age at recording ranged between four and 16 months, and duration of the phenomena ranged between two weeks and 19 months. In total, 85% infants had normal neurodevelopment at onset and follow-up (mean follow-up: 31.47 months) and 15% presented with neuropsychological or neurosensory deficits. We distinguished four different patterns of movements: movement of the head in 50%, shuddering attacks in 30%, tonic brief contractions of the trunk and limbs in 10%, and elevation of the shoulders in 10%. These motor phenomena do not affect neurological status and are not associated with developmental delay. Considering that clinical interpretation may be challenging, especially relative to epileptic seizures, we present an explanatory video of these characteristic events. We also propose a new definition that is simple to remember: "transient infant movements" (TIM).

Many technical problems, related to both imaging instrumentation and contrast agents, have to be taken into account before attempting non-invasive evaluation of myocardial perfusion by intravenous contrast media injection. Potentials and pitfalls of first generation contrast agents (i.e. Levovist, Schering AG, Berlin, Germany) using intermittent harmonic angio imaging and of second generation contrast media (i.e. SonoVue, Bracco SpA, Milan, Italy) using real-time perfusion imaging in the non-invasive assessment of myocardial perfusion were described and discussed. We still need more solid data before introducing intravenous myocardial echocardiography into the clinical arena. However, convincing data from several research laboratories are paving the way for the widespread use of this new method in clinical practice.