Manifold analysis of the P-wave changes induced by pulmonary vein isolation during cryoballoon procedure.

BACKGROUND/AIM: In atrial fibrillation (AF) ablation procedures, it is desirable to know whether a proper disconnection of the pulmonary veins (PVs) was achieved. We hypothesize that information about their isolation could be provided by analyzing changes in P-wave after ablation. Thus, we present a method to detect PV disconnection using P-wave signal analysis. METHODS: Conventional P-wave feature extraction was compared to an automatic feature extraction procedure based on creating low-dimensional latent spaces for cardiac signals with the Uniform Manifold Approximation and Projection (UMAP) method. A database of patients (19 controls and 16 AF individuals who underwent a PV ablation procedure) was collected. Standard 12-lead ECG was recorded, and P-waves were segmented and averaged to extract conventional features (duration, amplitude, and area) and their manifold representations provided by UMAP on a 3-dimensional latent space. A virtual patient was used to validate these results further and study the spatial distribution of the extracted characteristics over the whole torso surface. RESULTS: Both methods showed differences between P-wave before and after ablation. Conventional methods were more prone to noise, P-wave delineation errors, and inter-patient variability. P-wave differences were observed in the standard leads recordings. However, higher differences appeared in the torso region over the precordial leads. Recordings near the left scapula also yielded noticeable differences. CONCLUSIONS: P-wave analysis based on UMAP parameters detects PV disconnection after ablation in AF patients and is more robust than heuristic parameterization. Moreover, additional leads different from the standard 12-lead ECG should be used to detect PV isolation and possible future reconnections better.

Macrophage-Dependent Interleukin-6-Production and Inhibition of IK Contributes to Acquired QT Prolongation in Lipotoxic Guinea Pig Heart.

In the heart, the delayed rectifier K current, IK, composed of the rapid (IKr) and slow (IKs) components contributes prominently to normal cardiac repolarization. In lipotoxicity, chronic elevation of pro-inflammatory cytokines may remodel IK, elevating the risk for ventricular arrythmias and sudden cardiac death. We investigated whether and how the pro-inflammatory interleukin-6 altered IK in the heart, using electrophysiology to evaluate changes in IK in adult guinea pig ventricular myocytes. We found that palmitic acid (a potent inducer of lipotoxicity), induced a rapid (~24 h) and significant increase in IL-6 in RAW264.7 cells. PA-diet fed guinea pigs displayed a severely prolonged QT interval when compared to low-fat diet fed controls. Exposure to isoproterenol induced torsade de pointes, and ventricular fibrillation in lipotoxic guinea pigs. Pre-exposure to IL-6 with the soluble IL-6 receptor produced a profound depression of IKr and IKs densities, prolonged action potential duration, and impaired mitochondrial ATP production. Only with the inhibition of IKr did a proarrhythmic phenotype of IKs depression emerge, manifested as a further prolongation of action potential duration and QT interval. Our data offer unique mechanistic insights with implications for pathological QT interval in patients and vulnerability to fatal arrhythmias.

Urine Gene Expression Profiles in Bladder Pain Syndrome Patients Treated with Triamcinolone.

BACKGROUND: The pathogenesis of bladder pain syndrome (BPS) remains incompletely defined, and there is no standard treatment for BPS as yet. OBJECTIVE: To gain detailed insight into the disease pathobiology of BPS through comparative gene expression analysis of urine from BPS patients versus control individuals and, furthermore, to determine the efficacy of triamcinolone treatment in BPS patients in terms of the gene expression profiles in urine. DESIGN, SETTING, AND PARTICIPANTS: A prospective pilot study including 21 urine samples from patients with Hunner's lesions (n=6) and controls (n=9) between January and August 2017. INTERVENTION: Triamcinolone treatment of BPS patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Urine samples from BPS patients were collected before (pretreatment group) and 2 wk after triamcinolone treatment (post-treatment group). Gene expression of urine sediment was analyzed using RNA sequencing. Pathways and biological processes in which differentially expressed genes are involved were analyzed. RESULTS AND LIMITATIONS: A total of 3745 genes were found to be differentially expressed between the three groups tested. Gene expression differences between controls and BPS samples (630 differentially expressed genes) were more pronounced than the differences between pre- and post-treatment BPS samples (197 differentially expressed genes). Gen Set Enrichment Analysis showed that differentially expressed genes in BPS patients (pretreatment), compared with controls, were enriched for some functional gene networks associated with several metabolic processes and ribosome biogenesis. The limited number of patients included may not accurately represent the BPS population. CONCLUSIONS: Gene expression profiles of urine sediment are able to discriminate between BPS and control patients. Moreover, we show that triamcinolone induces changes in urine gene expression profiles. PATIENT SUMMARY: In this report, we looked at gene expression profiles of urine sediment from patients with Hunner's lesions, before and after triamcinolone treatment, and control individuals. We found that urine gene expression profiles are able to discriminate Hunner's lesions patients from controls. Furthermore, we report, for the first time, that triamcinolone treatment of patients with Hunner's lesions induces changes in bladder gene expression profiles that can be observed in urine samples.

Pain relief after triamcinolone infiltration in patients with bladder pain syndrome with Hunner's ulcers.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is a chronic condition with severe implications in the patient's quality of life with no definitive treatment. Our objective was to assess pain relief after triamcinolone injection in patients with BPS with Hunner's ulcers (HU). METHODS: Retrospective study of 20 consecutive patients with BPS treated at the Hospital Clinic of Barcelona with triamcinolone injection with flexible cystoscope between 2015 and 2016. Pain was assessed according to the visual analog scale (VAS) (0-10) before and after treatment. Outcomes were compared using Student's t test for paired samples. RESULTS: Twenty-seven procedures were performed in 20 patients, who were followed up for a median of 7 months (range 1-15). Median age was 75 years (52-86), and median time from diagnosis to treatment was 4.5 years (1-7). Fifteen (75 %) patients had received treatment with corticoid injection for BPS before entering the study. Pre- and postreatment VAS was 8 and 2.5 (p < 0.001), respectively. Pre -and postreatment VAS in those with muscular pain was 8 and 5 (p = 0.012), respectively and in those without muscular pain was 8 and 2 (p < 0.001), respectively. Three (15 %) patients required retreatment due to nonresponse and 5 (25 %) patients for pain recurrence after 4 months (3.5-8). Four of them (50 %) were performed with triamcinolone injection again. Seven of ten patients (70 %) followed for ≥8 months required at least one retreatment. CONCLUSION: Triamcinolone injection for HU in patients with BPS is associated with significant pain reduction. However, most patients will require retreatment.

Intraoperative prognostic factors and atypical patterns of recurrence in patients with upper urinary tract urothelial carcinoma treated with laparoscopic radical nephroureterectomy.

Objective The aims of this study were to identify clinical, intraoperative and pathological prognostic factors for predicting extraurothelial recurrence and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone laparoscopic radical nephroureterectomy (LRNU), and to investigate the site-specific patterns of recurrence and the associated outcomes. Materials and methods A retrospective revision was undertaken of 117 consecutive patients who had undergone transperitoneal LRNU for UTUC between 2007 and 2012. Univariate and multivariate Cox regression analyses were used to identify prognostic factors and Kaplan-Meier was used to estimate CSS. Results With a median follow-up of 20 months, 36 patients (30%) developed extraurothelial recurrence (local and/or distant). In the multivariate analysis, entering the urinary tract during LRNU was related to local recurrence (p = 0.04), management of the distal ureter to CSS (p = 0.003), pathological stage and positive margins to local (p = 0.001, p = 0.013), distant (p = 0.028, p = 0.009) and global recurrence (p = 0.05, p = 0.012) and CSS (p = 0.011, p = 0.042), and multifocality to distant recurrence (p = 0.024). Median time to recurrence was 11.4 months after LRNU. Of 36 patients with progression, 23 (64%) had simultaneous local and distant recurrence and eight had atypical metastases: two port-site metastases, five peritoneal, two subcutaneous and two abdominal wall implants. The 5 year CSS was 61% for all patients with UTUC and 9% for those with recurrence. Conclusions Intraoperative events could have a negative impact on the oncological outcomes of patients with UTUC treated with LRNU. The use of laparoscopy for advanced UTUC may be related to atypical ways of spreading.