Background:Ventricular tachycardias (VTs) associated with scar tissue involve reentry mechanisms influenced by both conduction abnormalities and repolarization heterogeneity. However, existing mapping techniques have predominantly focused on conduction delay. Methods:This retrospective study analyzed 33 consecutive cases of catheter ablation for sustained VT. The EnSite system was employed to measure repolarization time (RT) with a high-pass filter setting of 0.05 Hz. We compared the characteristics and concordance rates of short RT areas, defined as white or red-colored regions, with those identified through conventional mappings in relation to ablation targets. These short RT areas were defined based on the longest interval from the QRS onset to the maximal dV/dt point of unipolar potentials, which was divided into eight equal segments. Results:Out of 31 VTs across 26 cases, we found that 18 (58%) of the identified ablation targets corresponded to deceleration zones (DZs). Of them, 16 (89%) also overlapped with areas of short RTs. Notably, among the remaining 13 VTs without ablation targets corresponding to DZs, 9 (69%) had ablation targets located in areas with short RTs. The distribution analysis revealed that 84% of short RT regions were located near the exit site, whereas 75% of DZs were situated near the entrance site. The distance between the two was 16 mm (interquartile range: 6.5-27.5 mm). Conclusion:This study underscored the potential of RT mapping in identifying ablation targets in scar-related VTs. Incorporating both repolarization heterogeneity and conduction delay could significantly enhance the understanding of the intricate circuits involved in these arrhythmias.

BACKGROUND:Cardiomyopathies and idiopathic ventricular fibrillation have traditionally been studied as distinct entities; however, emerging evidence suggests that arrhythmias may represent an early manifestation of cardiomyopathy. The clinical utility of genetic testing in these conditions requires comprehensive evaluation. METHODS:We retrospectively analyzed 51 consecutive patients with idiopathic cardiomyopathies and/or idiopathic ventricular fibrillation who were admitted between 2020 and 2024. Genetic testing was performed using either whole-exome sequencing or targeted gene panels. Clinical characteristics, myocardial biopsy findings, and outcomes-including arrhythmia recurrence following catheter ablation-were assessed in relation to the presence of pathogenic or likely pathogenic (P/LP) genetic variants. RESULTS:P/LP variants were identified in 24 % of patients. Those harboring P/LP variants had a higher prevalence of family history (58 % vs. 21 %, p = 0.012). No significant difference in myocardial interstitial fibrosis was observed between P/LP carriers and non-carriers. Patients with P/LP variants exhibited significantly earlier clinical manifestations, including diagnosis, heart failure onset, and arrhythmic events (all p < 0.05). However, P/LP variant status did not significantly affect recurrence rates after catheter ablation for atrial or ventricular tachyarrhythmias. All P/LP variant carriers were diagnosed before age 60 years. CONCLUSIONS:P/LP genetic variants are associated with earlier disease onset; however, they do not appear to influence the severity of myocardial fibrosis or the recurrence of arrhythmias following catheter ablation. Genetic testing is recommended for younger patients presenting with cardiomyopathy, although further investigation is warranted to clarify its impact on therapeutic responses.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, is characterized by the formation of non-caseating granulomas affecting multiple organs. Accumulating evidence implicates Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes) as a potential microbial trigger. The consistent detection of C. acnes within sarcoid granulomas, along with associated Th1-polarized immune responses, indicates that latent intracellular persistence and reactivation of this commensal bacterium may drive granulomatous inflammation. This bacterium can persist intracellularly within macrophages and dendritic cells and, upon reactivation, may induce Th1/Th17-dominant immune responses in genetically and immunologically susceptible individuals. Immune dysregulation, including deficient C. acnes-specific regulatory T cell (Treg) responses, may underlie the unchecked effector activity that sustains inflammation. Enhanced C. acnes-specific T-cell reactivity, including elevated interferon-γ and interleukin-2 production, is observed in some patients, supporting this hypothesis. Although direct evidence for C. acnes-specific Tregs and antigen-specific T-cell responses is limited, immune dysregulation involving impaired tolerance is thought to contribute to the heterogeneity of sarcoidosis, which ranges from spontaneous remission to chronic fibrotic progression. Recent advances in diagnostic tools, including P. acnes-specific monoclonal antibody immunostaining and T-cell assays specific to C. acnes, offer promising approaches for detecting microbial involvement. These developments highlight the importance of etiology-driven treatment strategies. As sarcoidosis likely comprises a spectrum of underlying causes, etiology-specific interventions are particularly warranted upon the identification of a defined trigger, such as C. acnes. This review explores the potential pathogenesis of sarcoidosis, focusing on latent microbial reactivation, immune dysregulation, and their diagnostic and therapeutic implications, and highlights opportunities for precision medicine.

BACKGROUND:Gastric cancer survival rates vary across countries due to differences in access to early diagnostic testing and healthcare quality. Endoscopy, though accurate, is not feasible for mass screening. The ABC method, which combines serum Helicobacter pylori (Hp) antibody and pepsinogen tests, has shown promise for gastric cancer risk stratification in Japan. However, its applicability in populations with diverse CagA status and subtypes remains uncertain. MATERIALS AND METHODS:This prospective study in Brazil evaluated the performance of the ABC method in an endoscopy-referred cohort with a heterogeneous distribution of Hp CagA status and subtypes. A recently validated immunohistochemical method was applied to formalin-fixed paraffin-embedded gastric biopsy samples to assess Hp infection, CagA expression, and CagA subtypes. Gastric pathology was evaluated using the updated Sydney System and OLGA/OLGIM staging and correlated with serum Hp antibody and pepsinogen levels in 586 patients, including 122 Japanese Brazilians. RESULTS:Immunohistochemistry achieved a 98% success rate (577/586). The prevalence of Hp infection was 48%, with Western-type CagA(+) (26%) and CagA(-) (18%) strains predominating. East Asian-type CagA(+) strains (4%) were observed primarily among Japanese Brazilians, particularly in second-generation individuals. Gastric pathology and serum markers differed significantly across CagA status and subtypes. Despite these differences, the ABC method's negative predictive values (NPVs) across all groups other than Group A (negative for both tests) remained high (97%/97% or 98%/100% for detecting OLGA/OLGIM stages ≥ II or ≥ III, and 94%/98% or 99%/100% for detecting antrum/corpus inflammation scores ≥ 2 or 3, respectively). CONCLUSIONS:These findings demonstrate the clinical relevance of CagA diversity for gastric cancer risk assessment. Although limited to an endoscopy-referred cohort, the ABC method reliably identified low-risk individuals (Group A) and may help reduce unnecessary endoscopies in screening programs, regardless of CagA status and subtypes. Broader, population-based studies are needed to validate its generalizability and optimize its implementation.

Ventricular fibrillation (VF) with no obvious heart disease, as determined by echocardiography, catheterization, or magnetic resonance imaging, termed idiopathic VF, accounts for approximately 10% of cases of aborted sudden cardiac death.1 Among them, Brugada syndrome or J-wave syndrome is recognized as subepicardial cardiomyopathy with distinctive electrocardiographic characteristics.2

Background: The safety and efficacy of atrial fibrillation (AF) ablation in individuals with heart failure (HF) with preserved ejection fraction (EF), particularly concerning the occurrence of post-procedural adverse events necessitating hospitalization, including anticoagulant-associated major bleeding, still lack conclusive determination. Methods: Data from patients with HF and AF who underwent catheter ablation for AF between 2019 and 2022 at our institution were retrospectively reviewed. All participants were divided into an EF < 50% group or an EF ≥ 50% group according to their baseline left ventricular EF. The composite incidence of the clinical events following catheter ablation was compared between the two groups: (1) all-cause death, (2) HF hospitalization, (3) stroke or systemic embolism, and (4) major bleeding. Results: A total of 122 patients (75 years old, 68 male) were included. Of them, 62 (50.8%) patients had an EF ≥ 50%. EF ≥ 50% was an independent predictor of the composite endpoint (adjusted odds ratio 6.07, 95% confidence interval 1.37–26.99, p = 0.018). The incidences of each adverse event were not significantly different between the two groups, except for a higher incidence of major bleeding in the EF ≥ 50% group (12.7% vs. 0%, p = 0.026). Conclusions: Among patients with HF coupled with AF, the incidence of adverse events following AF ablation proved notably elevated in patients with EF ≥ 50% in contrast to their counterparts with EF < 50%. This disparity primarily stems from a heightened occurrence of major bleeding within the EF ≥ 50% cohort. The strategy to reduce adverse events, especially in patients with EF ≥ 50%, remains the next concern.

Abstract Background Oxidative stress is associated with atrial fibrillation recurrence following catheter ablation. Urinary isoxanthopterin (U‐IXP) is one of the noninvasive markers which reflect the reactive oxygen species; however, its ability to predict atrial tachyarrhythmias (ATAs) occurrence following catheter ablation remains uncertain. Methods Among the patients who received scheduled catheter ablation for atrial fibrillation, baseline U‐IXP levels were measured just before the procedure. The prognostic impact of baseline U‐IXP upon postprocedural ATAs occurrence was investigated. Results Among 107 patients (71 years old, 68% men), baseline U‐IXP level was 0.33 nmol/gCr on the median. During a mean of 603 days of follow‐up, 32 patients had ATAs. Baseline higher U‐IXP was independently associated with the occurrence of ATAs following catheter ablation with a hazard ratio of 4.69 (95% confidence interval: 1.82–12.37, p = .001) adjusted for the left atrial diameter, a persistent type, and hypertension which were potential confounders, with a cutoff of 0.46 nmol/gCr, which stratified cumulative incidence of ATAs occurrence ( p < .001). Conclusion U‐IXP can be used as the noninvasive predictive biomarker for ATAs following catheter ablation for atrial fibrillation.

The therapeutic strategy for sustained ventricular tachycardia (VT) during left ventricular assist device usage remains unclear. We encountered a patient with durable left ventricular assist device who presented sustained VT. Electrophysiological mapping was able to be established appropriately owing to the robust mechanical hemodynamics support despite inter-device interference. The three-dimensional activation map of clinically documented VT demonstrated that the propagation exited from the right ventricular apex through the critical isthmus located at the epicardium or interventricular septum, which was successfully treated by catheter ablation at the exit site. Further experiences like ours should be accumulated to establish a therapeutic strategy.

Background: Therapeutic strategy using catheter ablation for ventricular tachyarrhythmias (VTAs) electrical storms in patients dependent on percutaneous mechanical circulatory support (MCS) has not yet been established.Methods: We reviewed the patients with or without requiring MCS who received urgent VTAs ablation in our in-stitute between January 2020 and May 2022. Electrophysiological and clinical outcomes were compared between those with and without requiring MCS.Results: Twenty procedures (16 patients, median 76 years, 13 males) were included. Six procedures using MCS underwent ablations and the other 14 procedures were performed without MCS. Although VTAs cycle lengths were not significantly different between the two groups, the incidence of hemodynamic stability was signifi-cantly higher in MCS group than in those without (83 % vs. 29 %, p = 0.024). Temporary MCS were explanted in all patients following the successful ablation, whereas the complication rates were higher in patients requiring MCS (67 % vs. 0 %, p = 0.001). Cumulative incidences of cardiovascular death and appropriate therapy of implant-able cardioverter defibrillator within 90 days following the procedures were not significantly different between the two groups (p = 0.071 and p = 0.063, respectively).Conclusion: Urgent ablation might be a feasible bail out option for those dependent on MCS suffering from VTAs, although physicians should be on high alert for device-related bleeding.(c) 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

There are currently no studies that have examined the clinicopathological factors in detail, including the histological images of the invasive front, and the risk of lymph node metastasis (LNM) in superficial oesophageal squamous cell carcinoma (SESCC). This study aimed to develop an algorithm that contributes to a better assessment of the risk of LNM and recurrence in SESCC. Clinicopathological factors, such as submucosal (SM) invasion distance, were examined in 88 surgically resected cases of SESCC. An SM invasion distance of 600 μm was the statistically best customer value for LNM ( p = 0.0043). To obtain a histological image of the invasive front, we evaluated modified tumour budding (MBD) by modifying the number of tumour foci constituent cells and foci in tumour budding. We also evaluated the smallest number of tumour foci. Using these factors, we developed an algorithm to predict the risk of LNM. The best algorithm was created using an SM invasion distance of 600 μm and an index of 5 or more foci consisting of five or fewer tumour cells in the MBD (MBD5 high-grade ≥ 5), which was also significantly associated with recurrence-free survival (p = 0.0305). Further study of the algorithm presented in this study is expected to improve the quality of life of patients by selecting appropriate additional treatments after endoscopic resection and appropriate initial treatment for SESCC.

Background Cag A-positive Helicobacter pylori isolated from human gastric mucosa is categorized as a Western or East Asian allele-type based on whether the cagA gene encodes an EPIYA-C or EPIYA-D motif. We aimed to differentiate between the 2 types of H. pylori by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) gastric biopsy samples. Materials and Methods We developed 2 monoclonal antibodies (mAbs) that detect either the EPIYA-C or EPIYA-D motif of the H. pylori CagA protein by IHC using FFPE tissues. FFPE tissue sections from 30 Japanese and 39 Brazilian gastric biopsy samples with H. pylori infection confirmed by Giemsa staining (moderate/severe in the Sydney classification system) were examined by IHC with the novel mAbs followed by polymerase chain reaction (PCR) for EPIYA-C or EPIYA-D using DNA extracted from adjacent tissue sections. Results Differentiation among Western and East Asian types and CagA-negative H. pylori was successful in most (97%) samples by IHC with the novel mAbs and commercially available mAbs that react with a species-specific lipopolysaccharide or a common CagA motif of H. pylori. The detection status of EPIYA-C/D motifs by IHC with the novel mAbs was consistent with the PCR results in 61 (88%) of 69 samples: EPIYA-C(+)/D(−) in zero Japanese and 26 Brazilian samples, EPIYA-C(−)/D(+) in 26 Japanese and 1 Brazilian sample, and EPIYA-C(−)/D(−) in 1 Japanese and 7 Brazilian samples. The detection sensitivity and specificity of IHC with each novel mAb compared with the PCR results were, respectively, 84% and 97% for EPIYA-C, and 97% and 95% for EPIYA-D. Conclusions The novel mAbs specific to each EPIYA-C or EPIYA-D motif differentiated between Western and East Asian types of CagA-positive H. pylori by IHC using FFPE tissues. Applying these novel mAbs to large numbers of archived pathology samples will contribute to elucidating the association of these allele types with gastric cancer.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are non-epithelial neuroendocrine neoplasms originating from the adrenal medulla and paraganglion of the sympathetic and parasympathetic nervous system, respectively. PCCs and PGLs show histological similarities with other epithelial neuroendocrine neoplasms and olfactory neuroblastomas (ONBs), and the differential diagnosis of PGLs is particularly difficult. Therefore, we compared the sensitivity of PHOX2A, PHOX2B, and tyrosine hydroxylase (TH) in the histopathological diagnosis of PCCs and PGLs immunohistochemically using the tissue microarrays of 297 neoplasms including PCCs, PGLs, neuroblastomas, ganglioneuromas, epithelial neuroendocrine neoplasms, and ONBs. Using cutoff values of 25%, 5%, and 5% of tumor cells expressing PHOX2A, PHOX2B, and TH, respectively, as positive, 40 of 51 PCCs, 32 of 33 parasympathetic/head and neck PGLs (HNPGLs), 17 of 19 sympathetic/thoracoabdominal PGLs (TAPGLs), and 12 of 152 epithelial neuroendocrine neoplasms, including 123 well-differentiated and 29 poorly differentiated neuroendocrine neoplasms, were PHOX2A-positive. All 51 PCCs, 33 HNPGLs, and 19 TAPGLs were PHOX2B-positive, while all 152 epithelial neuroendocrine neoplasms were PHOX2B-negative. Moreover, 50 of 51 PCCs, 13 of 33 HNPGLs, all TAPGLs, and 12 of 152 epithelial neuroendocrine neoplasms were TH-positive. All ONBs were negative for PHOX2A, PHOX2B, and TH. PHOX2B was the most sensitive and specific diagnostic marker for PCCs and PGLs among PHOX2A, PHOX2B, and TH. PHOX2B can facilitate identification of PCCs and PGLs from epithelial neuroendocrine neoplasms and ONBs, especially in the case of HNPGLs, in which TH is often negative.

Cichlids include hundreds of species with a high economic value for aquaculture. These fish are subjected to intensive trade and farming that expose them to the risk of infectious diseases. This work focuses on ornamental cichlids held in an aquarium commercial facility presenting emaciation, in order to evaluate the presence of lesions in fish skin and organs. The fish were sampled during routine management activities and subjected to pathological and molecular investigations. The presence of lymphocystis disease virus, typically associated with cutaneous nodular disease, was ruled out. Histologically, they presented granulomas in the spleen, sometimes extending to the other visceral organs. Bacterial heat-shock protein 65 PCR products were detected in tissues associated, in the majority of cases, with granulomas; molecular investigation identified Mycobacterium spp. in two cases and Cutibacterium acnes in seven cases. Immunoreactivity to anti-Mycobacterium and anti-C. acnes antibodies was detected within granulomas. The presence of C. acnes within granuloma is elucidated for the first time in fish; however, similarly to what is found in humans, this bacterium could be harmless in normal conditions, whereas other contributing factors would be required to trigger a granulomatogenous response. Further confirmation by bacterial culture, as well as using large-scale studies in more controlled situations, is needed.

We report two cases of eyebrow granulomas in patients who underwent a permanent eye makeup procedure. A rash was observed 16 months after the procedure in Case 1, and 10 years after the procedure in Case 2. Histopathologically, both patients exhibited noncaseating epithelioid cell granulomas. In Case 1, most of the black-brown granules of the permanent makeup were not present in the granulomas but were localized in the upper dermis. In contrast, in Case 2, some of the black-brown granules were phagocytized in the granulomas, preferentially within the giant cells. Based on systemic examinations, the patients from Cases 1 and 2 were diagnosed with sarcoidosis and sarcoidal foreign body reaction, respectively. To clarify the pathogenesis of our cases, we performed immunohistochemistry using commercially available monoclonal antibodies specific to Cutibacterium acnes, previously Propionibacterium acnes (PAB), and Mycobacteria (LAM antibody). PAB antibody results were positive in granulomas only in Case 1, and the LAM antibody results were negative in both cases. Immunohistochemical detection of C. acnes in granulomas could provide useful information for differentiating between cutaneous sarcoidosis and sarcoidal foreign body reactions.

A 46-year-old woman with uveitis was referred to our respiratory diseases department in July 2018. Her medical history included transient bilateral hilar mediastinal lymphadenopathy (BHL) and multiple pulmonary nodules in May 2013 during pegylated interferon-alpha and ribavirin treatment for chronic hepatitis C infection. Five years post-treatment, chest X-ray revealed BHL and nodular recurrence. A biopsy of the subcutaneous buttock nodules revealed scattered non-caseating epithelioid granulomas with positive PAB immunohistochemical staining. This seem to be the first report of Propionibacterium acnes-associated sarcoidosis possibly initially triggered by interferon-alpha therapy. Understanding the mechanisms underlying interferon-triggered P. acnes-associated sarcoidosis may clarify the sarcoidosis immunopathogenesis.

Background and objectives: Current guidelines criteria do not satisfactorily discriminate responders to cardiac resynchronization therapy (CRT). QRS amplitude is an established index to recognize the severity of myocardial disturbance and might be a key to optimal patient selection for CRT. Materials and Methods: (1) Initial R-wave amplitude, (2) S-wave amplitude, and (3) a summation of maximal R- or R′-wave amplitude and S-wave amplitude were measured at baseline. These parameters were averaged according to right (V1 to V3) or left (V4 to V6) precordial leads. The impact of these parameters on response to CRT, which was defined as a decrease in left ventricular end-systolic volume ≥15% at six-month follow-up, was investigated. Results: Among 47 patients (71 years old, 28 men) who received guideline-indicated CRT implantation, 25 (53%) achieved the definition of CRT responder. Among baseline electrocardiogram parameters, only the higher S-wave amplitude in right precordial leads was an independent predictor of CRT responders (odds ratio: 2.181, 95% confidence interval: 1.078–4.414, p = 0.030) at a cutoff of 1.44 mV. The cutoff was independently associated with cumulative incidence of heart failure readmission and appropriate electrical defibrillation following CRT implantation (p < 0.05, respectively). Conclusions: Prominent S-wave in right precordial leads might be a promising index to predict left ventricular reverse remodeling and greater clinical outcomes following CRT implantation.

We report a case of a pulmonary necrotizing sarcoid granulomatosis (NSG)-like lesion possibly associated with coinfection of Mycobacterium avium and Propionibacterium acnes. A solitary nodule in the right middle lobe of the lung was notable for coagulative necrosis with aggregates of sarcoid-like epithelioid granulomas. Small arteries were damaged by granulomas. Both M. avium and P. acnes were detected in the lesion. Furthermore, more P. acnes genomes were detected in the granulomas than in the non-lesion lung. These findings blur the pathophysiologic boundaries among NSG, sarcoidosis, and mycobacteriosis, and suggest that NSG needs to be recognized as continuous spectra of sarcoidosis/mycobcteriosis.