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Implantable loop recorders (ILRs) are increasingly used to evaluate patients with unexplained syncope. Identification of all predictors of bradycardic syncope and consequent permanent pacemaker (PPM) insertion is of substantial clinical interest as patients in the highest risk category may benefit from upfront pacemaker insertion. We performed a systematic review and meta-analysis to identify risk predictors for PPM insertion in ILR recipients with unexplained syncope. An electronic database search (MEDLINE, Embase, Scopus, Cochrane) was performed in June 2023. Studies evaluating ILR recipients with unexplained syncope and recording risk factors for eventual PPM insertion were included. A random effects model was used to calculate the pooled odds ratio (OR) for clinical and electrocardiographic characteristics with respect to future PPM requirement. Eight studies evaluating 1007 ILR recipients were included; 268 patients (26.6%) underwent PPM insertion during study follow-up. PPM recipients were older (mean age, 70.2 ± 15.4 years vs 61.6 ± 19.7 years; P <.001). PR prolongation on baseline electrocardiography was a significant predictor of PPM requirement (pooled OR, 2.91; 95% confidence interval, 1.63–5.20). The presence of distal conduction system disease, encompassing any bundle branch or fascicular block, yielded a pooled OR of 2.88 for PPM insertion (95% confidence interval, 1.53–5.41). Injurious syncope and lack of syncopal prodrome were not significant predictors of PPM insertion. Sinus node dysfunction accounted for 62% of PPM insertions, whereas atrioventricular block accounted for 26%. Approximately one-quarter of ILR recipients for unexplained syncope require eventual PPM insertion. Advancing age, PR prolongation, and distal conduction disease are the strongest predictors for PPM requirement. [Display omitted] [ABSTRACT FROM AUTHOR]

Differentiation between ventricular tachycardia (VT) and supraventricular tachycardia (SVT) with aberrancy based on the 12‑lead ECG alone can be imprecise. Implantable cardiac defibrillators (ICD) may be inserted for presumed VT, particularly in patients with syncopal presentation or atypical aberrancy patterns. Accurate diagnosis of these patients facilitated by an electrophysiology study (EPS) may alter diagnosis and management. We present a prospective collection of cases across 3 cardiac centers of consecutive patients with WCT presumed to be VT who were referred for consideration of an ICD, and in whom further evaluation including an EPS ultimately demonstrated SVT with aberrancy as the culprit arrhythmia. 22 patients were identified (17 male, mean age 50±13 years. Available rhythm data at the time of referral was presumptively diagnosed as monomorphic VT in 16 patients and polymorphic VT in 6 patients. Underlying structural heart disease was present in 20 (91%). EPS resulted in a diagnosis of SVT with aberrancy in all cases: comprising AV nodal re-entry tachycardia (n=10), orthodromic reciprocating tachycardia (n=3), focal atrial tachycardia (n=3), AF/AFL (n=3) and 'double fire' tachycardia (n=2). 21 (95%) patients underwent successful ablation. All patients remained free of arrhythmia recurrence at a median of 3.4 years of follow-up. ICD insertion was obviated in 18 (82%) patients, with 1 patient proceeding to ICD extraction. SVT with atypical aberrancy may mimic monomorphic or polymorphic VT. Careful examination of all available rhythm data and consideration of an EPS can confirm SVT and obviate the need for ICD therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Sex-specific outcomes after catheter ablation (CA) for atrial fibrillation (AF) have reported conflicting findings. We examined the impact of female sex on outcomes in patients with persistent AF (PsAF) from the Catheter Ablation for Persistent Atrial Fibrillation: A Multicentre Randomized Trial of Pulmonary Vein Isolation vs PVI with Posterior Left Atrial Wall Isolation (CAPLA) randomized trial. A total of 338 patients with PsAF were randomized to pulmonary vein isolation (PVI) or PVI with posterior wall isolation (PWI). The primary outcome was arrhythmia recurrence at 12 months. Clinical and electroanatomical characteristics, arrhythmia recurrence, and quality of life were compared between women and men. Seventy-nine women (23.4%; PVI 37; PVI + PWI 42) and 259 men (76.6%; PVI 131; PVI + PWI 128) underwent AF ablation. Women were older {median age 70.4 (interquartile range [IQR] 64.8–74.6) years vs 64.0 (IQR 56.7–69.7) years; P <.001} and had more advanced left atrial electroanatomical remodeling. At 12 months, arrhythmia-free survival was lower in women (44.3% vs 56.8% in men; hazard ratio 1.44; 95% confidence interval 1.02–2.04; log-rank, P =.036). PWI did not improve arrhythmia-free survival at 12 months (hazard ratio 1.02; 95% confidence interval 0.74–1.40; log-rank, P =.711). The median AF burden was 0% in both groups (women: IQR 0.0%–2.2% vs men: IQR 0.0%–2.8%; P =.804). Health care utilization was comparable between women (36.7%) and men (30.1%) (P =.241); however, women were more likely to undergo a repeat procedure (17.7% vs 6.9%; P =.007). Women reported more severe baseline anxiety (average Hospital Anxiety and Depression Scale [HADS] anxiety score 7.5 ± 4.9 vs 6.3 ± 4.3 in men; P =.035) and AF-related symptoms (baseline Atrial Fibrillation Effect on Quality-of-Life Questionnaire [AFEQT] score 46.7 ± 20.7 vs 55.9 ± 23.0 in men; P =.002), with comparable improvements in psychological symptoms (change in HADS anxiety score −3.8 ± 4.6 vs −3.0 ± 4.5; P =.152 (change in HADS depression score −2.9 ± 5.0 vs −2.6 ± 4.0; P =.542) and greater improvement in AFEQT score compared with men at 12 months (change in AFEQT score +45.9 ± 23.1 vs +39.2 ± 24.8; P =.048). Women undergoing CA for PsAF report more significant symptoms and poorer quality of life at baseline than men. Despite higher arrhythmia recurrence and repeat procedures in women, the AF burden was comparably low, resulting in significant improvements in quality of life and psychological well-being after CA in both sexes. [ABSTRACT FROM AUTHOR]

Single-cell profiling technologies provide an unprecedented resolution in investigating the coordinated compositional and state alterations of immune and stromal components in response to cancer therapies on the tumor microenvironment, enabling a holistic and more nuanced understanding of treatment response and resistance. Multimodal characterization of the heterogeneity of baseline and perturbed adaptive immune populations, especially T cells, offers a foundation for the discovery of the most actionable therapeutic targets. Key players in the tumor microenvironment (TME) outside of the adaptive immune populations, including cancer-associated fibroblasts and macrophages, have emerged as effective mediators of cancer therapeutic response or resistance, frequently dependent on the crosstalk with T and B lymphocytes. Tumor-targeting treatments demonstrate widespread TME-modulating effects, often indirectly through consequent immunostimulating signaling elicited by remodeled tumor cells, justifying a combinatorial administration with immunotherapies. Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments are endowed with comprehensive mechanistic insights when decoded at the single-cell level, aiming to drive forward future research directions on personalized treatments. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy has become the standard treatment for locally advanced gastric cancer. The tumor regression grade system is an effective and widely used tool for the evaluation of treatment response to neoadjuvant chemotherapy. However, whether tumor regression grade could be predicted using clinical characteristics is uncertain. A total of 287 locally advanced gastric cancer patients from 2014 to 2021 were retrospectively included. According to the College of American Pathologists' tumor regression grade system, patients were classified into response group (tumor regression grade 0–1) and non-response group (tumor regression grade 2–3). Associations between clinical characteristics and neoadjuvant chemotherapy response were performed by the logistic regression model. The Kaplan–Meier method was used to estimate the survival. A prediction scoring system was constructed based on the β coefficients of multivariate analysis. The receiver operating characteristic curve and decision curve analysis were used to evaluate the performance of the predictive scoring system. Survival analysis showed that patients with tumor regression grades 0 to 1 had significantly better disease-free survival and overall survival than the tumor regression grades 2 to 3. Tumor differentiation, ycT stage, immunotherapy, and lymph node regression were independent predictors of pathological response to neoadjuvant chemotherapy. We further developed a scoring system to predict the tumor regression grade. The receiver operating characteristic and decision curve analysis showed good predictive performance of the scoring system. Lymph node regression could be used as a predictor for pathological response. We developed a scoring system to predict the treatment response of patients with gastric cancer receiving neoadjuvant chemotherapy. The scoring system based on the predictors could provide guidance for making clinical decisions. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes. We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (1) immune-targeted single-cell RNA sequencing (n = 20 patients) and (2) protein expression profiling by a targeted antibody panel for mass cytometry (n = 12 patients). We also generated matched V(D)J (variable, diversity, and joining gene segments) sequencing of T and B cells along CD45+ immunocytes. We found that compared to non-GSRCC, the GSRCC TIME appears to be quiescent, where both CD4+ and CD8+ T cells are difficult to be mobilized, which further impairs the proper functions of B cells. CXCL13, mainly produced by follicular helper T cells, T helper type 17, and exhausted CD8+ T cells, is a central coordinator of this transformation. We show that CXCL13 expression can predict the response to immune checkpoint blockade in GC patients, which may be related to its effects on tertiary lymphoid structures. Our study provides a comprehensive molecular portrait of immune cell compositions and cell states in advanced GC patients, highlighting adaptive immune irresponsiveness in GSRCC and a mediator role of CXCL13 in TIME. Our targeted single-cell transcriptomic and proteomic profiling represents a powerful approach for TIME-oriented translational research. [Display omitted] Gastric signet-ring cell adenocarcinoma is a rare gastric cancer subtype associated with poor patient survival. We provide the first molecular portrayal of immune components in this disease through integrative single-cell transcriptomic and proteomic profiling. [ABSTRACT FROM AUTHOR]