Primary Ablation Research Articles

An international physician survey of current ablation practices in atrial fibrillation: An AIM-AF substudy

BackgroundPractice guidelines recommend ablation (ABL) in atrial fibrillation (AF) for rhythm control. Guidance for antiarrhythmic drugs (AADs) post-ABL is limited. ObjectiveThe purpose of this study was to determine AAD and ABL practices in the United States and Europe. MethodsAn online survey of experienced cardiologists (CDs) (n = 360) and interventional electrophysiologists (EPs) (n = 269) was conducted. AAD- and ABL-related survey questions and responses were analyzed. ResultsABL was preferred more often as first-line AF therapy (Rx) by US CDs/EPs (P ≤.001). ABL was selected to avoid AAD Rx by 46% (50% CDs, 40% EPs); to prevent AF progression by 41% (36% CDs, 47% EPs); and for superior efficacy by 28% (27% CDs, 30% EPs). ABL was used by 9% in asymptomatic AF (9% CDs, 10% EPs), by 14% in subclinical AF (13% CDs, 14% EPs), and by 17% for first AF event (15% CDs, 18% EPs). Primary ABL was preferred in heart failure by 38%. Comorbidities, age, and left atrial size were limitations for ABL by 48%, 40%, and 38%, respectively. AADs were used after ABL for AF/atrial tachycardia (AT) prophylaxis by 34% for 3–6 months and 29% for 1–2 months. AADs were given for a single AF recurrence by 34%, bridging to re-ABL by 32%, and long-term Rx by 34%. AF/AT post-ABL was most often managed with amiodarone (42%–48%). ConclusionABL was frequently preferred over AADs in symptomatic AF but notably also was used for asymptomatic and subclinical AF. Post-ABL AAD Rx for AF prophylaxis or recurrence was frequent, with empiric amiodarone being the most often selected AAD.

Investigation of High Frequency Irreversible Electroporation for Canine Spontaneous Primary Lung Tumor Ablation.

In this study, the feasibility of treating canine primary lung tumors with high-frequency irreversible electroporation (H-FIRE) was investigated as a novel lung cancer treatment option. H-FIRE is a minimally invasive tissue ablation modality that delivers bipolar pulsed electric fields to targeted cells, generating nanopores in cell membranes and rendering targeted cells nonviable. In the current study, canine patients (n = 5) with primary lung tumors underwent H-FIRE treatment with an applied voltage of 2250 V using a 2-5-2 µs H-FIRE waveform to achieve partial tumor ablation prior to the surgical resection of the primary tumor. Surgically resected tumor samples were evaluated histologically for tumor ablation, and with immunohistochemical (IHC) staining to identify cell death (activated caspase-3) and macrophages (IBA-1, CD206, and iNOS). Changes in immunity and inflammatory gene signatures were also evaluated in tumor samples. H-FIRE ablation was evident by the microscopic observation of discrete foci of acute hemorrhage and necrosis, and in a subset of tumors (n = 2), we observed a greater intensity of cleaved caspase-3 staining in tumor cells within treated tumor regions compared to adjacent untreated tumor tissue. At the study evaluation timepoint of 2 h post H-FIRE, we observed differential gene expression changes in the genes IDO1, IL6, TNF, CD209, and FOXP3 in treated tumor regions relative to paired untreated tumor regions. Additionally, we preliminarily evaluated the technical feasibility of delivering H-FIRE percutaneously under CT guidance to canine lung tumor patients (n = 2). Overall, H-FIRE treatment was well tolerated with no adverse clinical events, and our results suggest H-FIRE potentially altered the tumor immune microenvironment.

The soluble ST2 level predicts risk of atrial fibrillation recurrences in long-term period after radiofrequency ablation

Background and objectives:The hypothesis of the study was the assumption that the serum levels of soluble ST2 (sST2) and growth differentiation factor (GDF-15) can be predictors of atrial fibrillation (AF) recurrence in long-term period after primary radiofrequency catheter ablation (RFA).MethodsOf the 165 patients included in the prospective follow-up, the final analysis included 131 patients whose follow-up duration reached 18 months after the end of the blanking period (3 months after RFA). The median age of patients was 59.0 (50.0; 64.0) years, and 80 (61%) were men. Paroxysmal AF was present in 103 (79%) and persistent AF in 28 (21%) patients. All patients underwent transthoracic and transesophageal echocardiography, and electroanatomic mapping was used to assess the area of low-voltage zones (LVZ). sST2 and GDF-15 levels were determined by ELISA using GDF-15/MIC-1 analytical kits (BioVender, Czech Republic) and Presage ST2 (Critical Diagnostics, USA) before RFA. After RFA, patients had regular follow-up visits at 3-6-9-12-18 months with 12-lead ECG or Holter ECG monitoring and with clinical evaluation. The primary endpoint was the occurrence of the first symptomatic AF recurrence (AFr) lasting > 30 s, recorded on an ECG or during daily ECG monitoring, after a blanking period.ResultsAt the 18-month follow-up, 47 patients (35.9%) had AFr. The groups with and without AFr didn`t differ in the LVZ area. The medians of NT-proBNP, GDF-15 and sST2 also didn`t differ significantly between the groups, but in patients with AFr, the proportion of those with sST2 ≥ 36 ng/ml (the border of the lower and middle terziles) was higher (p = 0.03). According to the one-factor Cox regression analysis, AFr were associated with four factors: AF history ≥ 1 year, early AFr (during the blanking period), left atrial appendage flow velocity (LAAFV) < 54 cm/sec and sST2 ≥ 36 ng/ml. In the multivariate Cox analysis two independent predictors of AFr were obtained: sST2 ≥ 36 ng/ml (HR = 3.8; 95% CI 1.5–9.8, p = 0.006) and LAAFV < 54 сm/sec (HR = 1.96; 95% CI 1.01–3.82, p = 0.048).ConclusionsSerum sST2 level with a cut-off value of 36 ng/ml or more can be used as a predictor of AF recurrence in the long-term period after primary RFA.

Simultaneous primary posterior urethral valves ablation and bladder neck incision may decrease kidney and bladder failure in long-term follow-up in patients with bladder neck hypertrophy and poor bladder function at presentation: report of 301 cases

ObjectivesTo investigate the effects of bladder neck incision (BNI) and primary valves ablation on long-term kidney and bladder function in children with posterior urethral valves (PUV) and bladder neck hypertrophy (BNH).Patients and methodsFrom 1997 to 2016, a total of 1381 children with PUV were referred to our tertiary hospital. Of these patients, 301 PUV patients with bladder neck hypertrophy need concurrent BNI and valve ablation. All patients were followed up every 3–6 months on regular basis in first 2 post-surgical years and annually then after. The paired t-test and chi-square test were used to perform statistical analysis with p value < 0.05 defined as the level of significance.ResultsMean age at diagnosis was 7.22 ± 2.45 months (ranging from 7 days to 15 months) with a mean follow-up of 5.12 ± 2.80 years. The incidence of hydronephrosis was decreased from 266 (88.3%) at the baseline to 73 (24.3%) patients in long-term follow-up. At baseline, 188 (62.5%) patients were diagnosed with VUR, which decreased to 20 (6.6%) individuals at the end of follow-up. Bladder and renal function were improved in follow-ups following concomitant PUV ablation and BNI. No Myogenic failure was depicted in all patients with BNH. No ureteric reimplantation was needed during the two decades follow-up.ConclusionSimultaneous valve ablation with BNI may present further profits in children with PUV and BNH particularly cases of BNH with poor bladder function at the time of presentation. This method can improve the results of urodynamic and imaging studies after the surgery. We hypothesize every child with PUV presentation who has concurrent vesicoureteral reflux, CKD or persistent hydrourethronephrosis may suffer from secondary bladder neck obstruction. This secondary bladder outlet obstruction must be managed through BNI as the surgical relief.

The effect of use of alpha-blockers in posterior urethral valve pediatric patients postvalve ablation in the absence of further outlet obstruction.

The objectives of this study were to detect whether the use of alpha-blockers in posterior urethral valve (PUV) pediatric patients after valve ablation will improve the persistent obstructive symptoms despite the absence of obstruction and if there are associated side effects of its use. Methods: A prospective, single-blinded randomized study was conducted at the urology department of two hospitals on 50 male children between September 2019 and June 2021 with PUV. All children were treated by endoscopic ablation of PUV using the cold knife and were followed clinically for voiding symptoms and with ultrasonography and laboratory tests. All patients underwent second-look cystoscopy 1 month after primary valve ablation to see residual valves as a routine procedure confirming no remnant of the valve and still complaining of obstructive symptoms. They were divided into two equal groups 25 patients each. Group A was given alpha-blockers and Group B placebo for 1 month. Marked improvement of obstructive symptoms in Group A reaching about 90% (21 patients), whereas no mentioned improvement in Group B was noticed with no side effects of both medication the alpha-blocker and the placebo during its use. The use of alpha-blockers improves the obstructive symptoms in pediatric patients with PUV after valve ablation and in the absence of any further urethral obstruction with no side effects noticed during the period of its use.

Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation

Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional surgical procedures, re-transplantation or die in the absence of a suitable regraft. Here, we investigate the role of the primary cilium, a highly specialised sensory organelle, in biliary injury leading to post-transplant biliary complications. Human biopsies were used to study the structure and function of primary cilia in liver transplant recipients that develop biliary complications (n= 7) in comparison with recipients without biliary complications (n= 12). To study the biological effects of the primary cilia during transplantation, we generated murine models that recapitulate liver procurement and cold storage, and assessed the elimination of the primary cilia in biliary epithelial cells in the K19CreERTKif3afl/fl mouse model. To explore the molecular mechanisms responsible for the observed phenotypes we used invitro models of ischemia, cellular senescence and primary cilia ablation. Finally, we used pharmacological and genetic approaches to target cellular senescence and the primary cilia, both in mouse models and discarded human donor livers. Prolonged ischemic periods before transplantation result in ciliary shortening and cellular senescence, an irreversible cell cycle arrest that blocks regeneration. Our results indicate that primary cilia damage results in biliary injury and a loss of regenerative potential. Senescence negatively impacts primary cilia structure and triggers a negative feedback loop that further impairs regeneration. Finally, we explore how targeted interventions for cellular senescence and/or the stabilisation of the primary cilia improve biliary regeneration following ischemic injury. Primary cilia play an essential role in biliary regeneration and we demonstrate that senolytics and cilia-stabilising treatments provide a potential therapeutic opportunity to reduce the rate of biliary complications and improve clinical outcomes in liver transplantation. Up to 25% of liver transplants result in biliary complications, leading to additional surgery, retransplants, or death. We found that the incidence of biliary complications is increased by damage to the primary cilium, an antenna that protrudes from the cell and is key to regeneration. Here, we show that treatments that preserve the primary cilia during the transplant process provide a potential solution to reduce the rates of biliary complications.

The impact of cardiac rehabilitation on atrial fibrillation recurrence after pulmonary vein isolation: results of a retrospective study

Abstract Background Although pulmonary vein isolation (PVI) is an extensively utilized atrial fibrillation (AF) treatment, many patients still experience AF recurrences. Multimorbidity care, including physical activity, may reduce recurrences. In Belgium, patients undergoing an ablation are entitled to a cardiac rehabilitation (CR) program after PVI, but not all do participate. More evidence that such (standardized) CR programs for AF patients after ablation can positively impact rhythm control is desirable. Purpose This study retrospectively investigated the impact of CR on AF recurrence after PVI. Methods We analysed an extensive database of a large Belgian tertiary care center with patients who underwent a primary PVI between 2007 and 2020 and who had a follow-up of at least 1 year. General cardiology follow-up included a 24h Holter monitoring 3 and 12 months after PVI. Patients were retrospectively divided into an intervention and control group based on their choice to participate in a standardized CR program. The Kaplan-Meier method was used to estimate the time-to-recurrence and event-free survival curves after the primary ablation. Differences between curves were tested with the log-rank test. Mann-Whitney U test was used to analyze continuous variables and the Chi-square test for categorical variables. Results In total, 1767 patients were included, of which 589 participated to CR and 1178 served as controls (median 64 (56-70) y, 68.9% male, median BMI 27.5 (24.7-30.7) kg/m2). There was no significant difference between CR and controls in median age (64y vs. 63y respectively; p=0.203), the proportion of male (57.9% vs. 47.0% respectively; p=0.111) and the proportion of paroxysmal AF (66.4% vs. 70.6% respectively; p=0.210). The proportion with recurrent AF at the end of study follow-up (with a three-month initial blanking period) in the CR and control group was similar (32.6% vs. 35.1% respectively; p=0.288), and also survival analysis demonstrated no significant difference (p=0.827; Figure 1). We noted a cross-over of the recurrence curves after about 1500 days, but the rate of AF recurrence was not different among CR and controls within the first year post-ablation (p=0.136) nor when analysed from day 365 until the end of the study (p=0.341) (Figure 2). There was no significant difference in AF recurrences between CR and controls for either paroxysmal AF (p= 0.551) or persistent AF (p=0.181) based on the survival analysis. Conclusions This retrospective analysis could not demonstrate reduced AF recurrence in post-PVI patients following a structured CR program. The unexpected crossover of curves could point to earlier AF detection in CR patients, while there might be long-term benefit of physical activity. Multivariable analysis will have to evaluate whether impact of CR is related to certain clinical patient characteristics, which might also have contributed to inclusion bias.Figure 1Figure 2

Pulsed-field ablation of atrial fibrillation in elderly and frail patients: procedural efficacy and safety from a single-center experience

Abstract Introduction The demographic data shows a growing population, mostly elderly and with multiple comorbidities, therefore becoming increasingly frail. In this context Atrial fibrillation (AF) is the predominant sustained arrhythmia, and over the years trans-catheter isolation of pulmonary veins (PVI) has become a crucial approach in AF treatment. Among the technologies and energy resources employed through the years to perform atrial fibrillation transcatheter ablation, a novel technique has recently begun to gain ground, specifically pulsed-field ablation (PFA). PFA employs sequential brief and high amplitude electrical pulses to induce selective and irreversible electroporation of the myocardium, leading to cell death. The high selectivity of the lesion, ensured by the lower electroporation threshold of myocardial tissue compared to adjacent anatomic structures, allows for a decrease in potential complications associated with conventional thermal ablation. Purpose To assess the efficacy and safety in the use of pulsed field ablation in a selected population of elderly and frail patients undergoing atrial fibrillation ablation. Method We conducted a retrospective study focusing on elderly and frail patients admitted to our centre for paroxysmal or persistent AF ablation. The inclusion criteria were: age greater than 75 years and a Clinical Frailty Scale ≥ 5. The study population consisted of 26 patients [male gender 18, mean age 78 ± 3 years] including 8 who were affected by an oncological or haematological disease at the time of admission. The majority of patients were affected by paroxysmal AF while two of them presented persistent AF (9%). The primary ablation endpoint was the pulmonary vein isolation (PVI) that was achieved by delivering an energy of 2 kV over 8 applications, employing an alternating approach between the two configurations of the basket and flower catheter for each individual vein. Results The short-term success, represented by the complete and verified electrical isolation of the veins was achieved in all 26 patients without any periprocedural complications. First-pass pulmonary vein isolation (FPI) was universally achieved among the patient in study, with a mean skin-to-skin procedural time of 70 ± 30 minutes. From the procedural data perspective, ablation was achieved using an average fluoroscopy time of 22 ± 8.4 minutes and an average dose area product (DAP) of 1320 cGy×cm2. Conclusions In elderly and frail patients, we assessed the efficacy and safety of ablative procedures using the PFA technique. Successful electrical PVI was achieved without additional touch-ups, thanks to a high FPI rate. This results in lower procedural times and shorter intra-operative radiation exposure. These data confer an augmented value within the elderly-frail population, wherein shorter procedural times contribute to a better postoperative course, characterized by reduced bed rest and shorter intra-hospitalization periods.

Ablation for malignant liver tumor using high-intensity focused ultrasound and radio-frequency: A meta-analysis.

Primary liver cancer is a major health issue, so finding the most effective treatment is vital. The present meta-analysis compares high-intensity focused ultrasound (HIFU) to radiofrequency (RF) ablation for primary liver cancer treatment. PubMed, MEDLINE, CNKI, VIP, and Wanfang were used to search for English and Chinese papers. After carefully confirming data completeness and applying inclusion and exclusion criteria, RevMan 5.3 was used to evaluate the included literature. Data analysis utilized a fixed-effects model for heterogeneity between 0.1 and 0.5. The meta-analysis included 304 patients: 119 had HIFU and 185 RF ablation. For primary liver cancer, HIFU and RF ablation were equally efficacious (odds ratio 1.02, 95% confidence interval [0.54, 1.92]). Overall survival, disease-free survival, and complications at 1, 2, and 3 years were not significantly different (odds ratio 0.72, 95% confidence range [0.04, 12.79], P= 0.82). The meta-analysis shows no significant difference in efficacy, long-term survival rates, or complication rates between HIFU and RF ablation for primary liver cancer, but more large-scale, high-quality randomized clinical trials are needed to prove their equivalence. Both therapy strategies seem promising, but additional information is needed to determine their respective merits.

Pulmonary vein capture is a predictor for long-term success of stand-alone pulmonary vein isolation with cryoballoon ablation in patients with persistent atrial fibrillation.

The mechanisms of AF development and progression are still not completely understood. Despite the relative efficacy of ablation, the risk of AF recurrence is substantial, particularly in patients with persistent AF (perAF). At present we do not have any reliable intra-procedural electrophysiologic predictors of long-term success of AF ablation other than pulmonary vein isolation. We evaluated selected intraprocedural pulmonary vein characteristics that may be helpful in future guidance of persistent AF ablation. 390 consecutive procedures using cryoballoon for initial AF ablation were divided by clinical presentation (paroxysmal or persistent AF), and by pulmonary vein (PV) response to pacing after completion of ablation (discrete electrogram elicited with pacing-"PV capture" or not-"Control"). Patients were followed (median 20 months) for recurrent atrial arrhythmias as the primary end point of the study. PV capture was identified in 20.3% and 17.1% and patients with paroxysmal and persistent AF respectively (ns). In patients with persistent AF presence of PV capture was associated with significantly better outcomes compared to patients without PV capture (p < 0.001). In the group "persistent AF and PV capture", an initial strategy of PV isolation and reisolation of the PVs (without additional lesions) for patients with recurrent atrial arrhythmias resulted in 20/23 (87%) patients in sinus rhythm off antiarrhythmic medications at study completion. In patients with paroxysmal AF, PV capture was not associated with outcome benefits. Specific electrophysiologic characteristics of PV (PV capture cycle length: PVCCL) did not have an impact on AF recurrence, although 25% shortening of PVCCL was observed after 60 s periods of pacing at short cycle lengths. No background demographic patient characteristic differences were identified between patients with vs. without PV capture. The presence of PV capture was associated with better outcomes in patients with persistent AF. PV capture may identify those patients with persistent AF in whom cryoballoon PV isolation alone is sufficient as an initial ablation procedure and as the primary ablation strategy for recurrent AF.

Supramolecular prodrug-like nanotheranostics with dynamic and activatable nature for synergistic photothermal immunotherapy of metastatic cancer

Synergistic photothermal immunotherapy has attracted widespread attention due to the mutually reinforcing therapeutic effects on primary and metastatic tumors. However, the lack of clinical approval nanomedicines for spatial, temporal, and dosage control of drug co-administration underscores the challenges facing this field. Here, a photothermal agent (Cy7-TCF) and an immune checkpoint blocker (NLG919) are conjugated via disulfide bond to construct a tumor-specific small molecule prodrug (Cy7-TCF-SS-NLG), which self-assembles into prodrug-like nano-assemblies (PNAs) that are self-delivering and self-formulating. In tumor cells, over-produced GSH cleaves disulfide bonds to release Cy7-TCF-OH, which re-assembles into nanoparticles to enhance photothermal conversion while generate reactive oxygen species (ROSs) upon laser irradiation, and then binds to endogenous albumin to activate near-infrared fluorescence, enabling multimodal imaging-guided phototherapy for primary tumor ablation and subsequent release of tumor-associated antigens (TAAs). These TAAs, in combination with the co-released NLG919, effectively activated effector T cells and suppressed Tregs, thereby boosting antitumor immunity to prevent tumor metastasis. This work provides a simple yet effective strategy that integrates the supramolecular dynamics and reversibility with stimuli-responsive covalent bonding to design a simple small molecule with synergistic multimodal imaging-guided phototherapy and immunotherapy cascades for cancer treatment with high clinical value.

Percutaneous ablation for adrenal metastasis from non-small-cell lung cancer: comparison between cryoablation and microwave ablation.

While cryoablation (CA) and microwave ablation (MWA) have both been implemented as approaches to the treatment of adrenal metastasis (AM), the outcomes associated with these two therapeutic strategies remain unclear. To compare the safety and efficacy of CA and MWA as treatments for AM in patients with non-small-cell lung cancer (NSCLC). Consecutive patients with AM secondary to NSCLC from January 2015 to December 2020 underwent CA or MWA. Treatment-related outcomes and complications were retrospectively compared between these groups. In total, 68 NSCLC patients with isolated AM were enrolled in this study, of whom 35 and 33 underwent treatment with CA and MWA, respectively. Primary complete ablation rates in the CA and MWA groups were 91.4% (32/35) and 93.9% (31/33) respectively (p = 1.000), while a 100% secondary complete ablation rate was observed for both groups. Hypertensive crisis incidence affected 11.4% (4/35) and 9.1% (3/33) of patients in the CA and MWA groups (p = 1.000), respectively, while 8 (22.9%) and 8 (24.2%) patients in these corresponding groups experienced local progression after ablation that was detected during the follow-up period (p = 0.893). Patients in the CA and MWA groups exhibited a median progression-free survival of 18 and 22 months, respectively (p = 0.411), while the corresponding median overall survival of patients in these groups was 25 and 29 months (p = 0.786). CT-guided CA and MWA appear to exhibit similar safety and efficacy profiles when employed to treat isolated AM in NSCLC patients.

Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo

Human pluripotent stem cell-derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both invitro and invivo organoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single-cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA-approved drug, effectively attenuated cyst formation invivo. This invivo organoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation.

Long-term Outcomes and Patient Satisfaction Following Salvage Robot-assisted Radical Prostatectomy: A Modern Perspective

Background and objectiveApproximately two-thirds of men who undergo primary treatment for prostate cancer (PC) will experience biochemical recurrence (BCR). Salvage robot-assisted radical prostatectomy (sRARP) offers curative treatment in this disease setting and men who choose this option may avoid palliative androgen deprivation therapy (ADT). The purpose of this study was to describe long-term outcomes and patient feedback following sRARP. MethodsWe reviewed data for consecutive men with biopsy-proven localized BCR who underwent sRARP and pelvic lymph node dissection at a single tertiary referral center between 2004 and 2021. Perioperative data, Clavien-Dindo complications, and functional outcomes were recorded. The Kaplan-Meier method was used to estimate prostate-specific antigen–free (≥0.2 ng/ml) survival (PSAFS) and metastasis-free survival (MFS). Three Likert-type items (score 1-5) from the validated Surgical Satisfaction Questionnaire-8 were distributed to patients postoperatively. Key findings and limitationsWe included 78 men, of whom 72 (92%) had undergone primary radiotherapy and six (8%) had received primary prostate ablation. Median follow-up was 10.1 yr (interquartile range 5.8–12.4). Final pathology identified ≥pT3N0M0 in 35 patients (45%) and positive margins in 23 (29%). The overall complication rate was 50%. Of the 26 (33%) major (grade ≥III) complications, anastomotic stricture (32%) was most common. The estimated 3-, 5-, and 10-yr survival rates were 85.6% and 80.2%, 83.5% for PSAFS (n = 11), and 74.1%, 83.5%, and 70.5% for MFS (n = 23), respectively. At last follow-up, postoperative ADT had been administered to 17 patients (22%), and 39 men (50%) remained alive a decade after sRARP. Continence and potency were maintained in 33/62 (53%) and 1/16 (6%) patients, respectively. Thirty-five respondents (45%) reported median questionnaire scores (≥4) in favor of sRARP. Limitations include the small single-center series and a single query point for patient feedback. Conclusions and clinical implicationsLong-term outcomes of sRARP suggest that the technical challenges and morbidity of the procedure are qualified by patient feedback and the opportunity to evade the morbidity and mortality of biochemically recurrent PC. Patient summaryWe reviewed the cancer outcomes and side effects of robot-assisted surgical removal of the prostate after treatment failure with radiation or ablation for prostate cancer. We found that this type of treatment has substantial risks and long-term side effects, but the surgery provides an opportunity to cure prostate cancer and/or avoid the consequences of indefinite hormonal treatment. Overall, most men who underwent this surgery were not disappointed with their decision despite the higher risks and consequences.

Atrial Fibrillation Ablation: Current Practice and Future Perspectives.

Catheter ablation to perform pulmonary vein isolation (PVI) is established as a mainstay in rhythm control of atrial fibrillation (AF). The aim of this review is to provide an overview of current practice and future perspectives in AF ablation. The main clinical benefit of AF ablation is the reduction of arrhythmia-related symptoms and improvement of quality of life. Catheter ablation of AF is recommended, in general, as a second-line therapy for patients with symptomatic paroxysmal or persistent AF, who have failed or are intolerant to pharmacological therapy. In selected patients with heart failure and reduced left-ventricular fraction, catheter ablation was proven to reduce all-cause mortality. Also, optimal management of comorbidities can reduce AF recurrence after AF ablation; therefore, multimodal risk assessment and therapy are mandatory. To date, the primary ablation tool in widespread use is still single-tip catheter radiofrequency (RF) based ablation. Additionally, balloon-based pulmonary vein isolation (PVI) has gained prominence, especially due to its user-friendly nature and established safety and efficacy profile. So far, the cryoballoon (CB) is the most studied single-shot device. CB-based PVI is characterized by high efficiency, convincing success rates, and a beneficial safety profile. Recently, CB-PVI as a first-line therapy for AF was shown to be superior to pharmacological treatment in terms of efficacy and was shown to reduce progression from paroxysmal to persistent AF. In this context, CB-based PVI gains more and more importance as a first-line treatment choice. Non-thermal energy sources, namely pulsed-field ablation (PFA), have garnered attention due to their cardioselectivity. Although initially applied via a basket-like ablation tool, recent developments allow for point-by-point ablation, particularly with the advent of a novel lattice tip catheter.

External validation and reliability assessment of posterior urethral morphology on initial voiding cystourethrogram as a predictor for infants with posterior urethral valves

The morphology of the bladder and posterior urethra on initial voiding cystourethrogram (VCUG) in posterior urethral valve (PUV) has been proposed as a meaningful early metric for short- and long-term kidney outcomes. Here, we seek to externally validate the proposed association and assess the reliability of PUV morphology characteristics. We reviewed our institutional database for patients managed for PUV between 2000 and 2022 and included those treated with primary ablation with at least 1 year of follow-up for kidney function. Each VCUG was evaluated by three independent raters for the height-width ratio of the bladder (HW-B), height-width ratio of the posterior urethra (HW-PU), and posterior-anterior urethral ratio (PA-UR), and trabeculation (none, fine, or coarse). We assessed the reliability in these with intra-class coefficient and Fleiss kappa for continuous and categorical data, respectively. We performed univariate analysis with nadir creatinine and five-year follow-up glomerular filtration rate (GFR). In total, 98 patients met inclusion criteria. The median age at diagnosis and ablation was 10 and 21 days, respectively. Patients with nadir creatinine <0.8mg/dL had higher follow-up GFR (101 vs. 20ml/min/1.73m2, p=0.04), and lower risk of CKD (odds ratio 14.7, p=0.002). The median value for HW-B was 1.4, median HW-PU was 2.1, and median PA-U was 4.7, There was significant inter-class agreement between all three measures of 0.80, 0.51, and 0.70 (p<0.001). The inter-rater agreement for bladder trabeculation was fair (Fleiss K=0.40, p<0.001). There was no statistically significant correlation between HW-B, HW-PU, PU-A with nadir creatinine (p=0.07, 0.33, 0.91) or 5-year GFR (0.27, 0.45, 0.62), respectively. There is significant interest in determining prognostic factors and metrics in PUV. The morphological characteristics on VCUG are reliable and is available information for all boys diagnosed with PUV, resulting in an attractive metric. While we do not demonstrate correlation with kidney outcomes, VCUG features warrant further attention as prognostic factors in PUV. PUV morphology on initial VCUG is a reliable metric of lower urinary tract deformity but is not associated with 5-year kidney outcomes.

Distinct immunoreactions after a primary tumor microwave ablation using different heating parameters in a VX2 tumor model.

Thermal ablation of solid tumors in situ can activate the immune system and produce a specific immune response against the tumor. Microwave ablation (MWA) with different parameters can ablate tumors with similar sizes and cause different local inflammatory effects. Our aim was to determine the immunological effects induced by different energy modes of MWA for a primary tumor. Seventy rabbits with VX2 tumors that were implanted subcutaneously underneath the right second nipple were treated with high-power MWA (40 W for 1 min), low-power MWA (20 W for 2 min), or surgical resection or were left without treatment (control). Survival time was evaluated by log-rank test. On day 14 after ablation, immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses. In addition, the cytokine patterns were identified by enzyme-linked immunosorbent assay. Tumor eradication was achieved completely in the MWA groups, as proven by nicotinamide adenine dinucleotide diaphorase staining. Compared with the three treatment groups, the control group had a significantly higher number of pulmonary metastases and worse survival; however, no significant difference was observed among the three treatment groups. More intra-tumoral and systemic CD4+ and CD8+ T-cells were induced in the MWA groups than in the control group. Compared with operation, MWA induced more systemic CD4+ T-cells. More intra-tumoral CD4+ and CD8+ T-cells and systemic CD4+ T-cells were induced by high-power MWA than by low-power MWA. Moreover, MWA increased the interleukin 2 (IL2) and IL12 levels and decreased the IL4, IL6, and IL10 levels. Importantly, the serum IL12 level was significantly higher after high-power MWA than after low-power MWA. High-power MWA enhanced the type 1 T helper immune response and may be selected for the treatment of solid tumors. Future studies are needed to confirm our results.

CMR-based analysis of atrial epicardial adipose tissue aids identification of a low-risk group for the presence of LA fibrosis

Abstract Introduction There is growing evidence that occurrence of atrial fibrillation (AF) is influenced by epicardial adipose tissue, which triggers left atrial (LA) remodeling through an inflammatory reaction, leading to dilatation and fibrosis. Identification of patients with advanced stage LA remodeling and fibrosis resulting in low voltage zones (LVZ) can contribute to individualized decision making in pulmonary vein isolation (PVI) treatment. Objective To establish a prediction model utilizing cardiac magnetic resonance (CMR) derived atrial epicardial adipose tissue quantification for the presence of LVZ during electroanatomic mapping that corresponds to LA fibrosis. Methods 66 patients admitted for primary AF ablation routinely underwent a preprocedural CMR scan. Dedicated adipose tissue enhancing sequences (2D fat/water separation) using short axis slices covering the LA were employed to create a 3D epicardial adipose tissue (EAT) model reconstruction. In addition, an LA angiography using gadolinium contrast was performed to create a 3D LA model. Model segmentation and volume quantification were performed with dedicated software (Figure 1). In the subsequent PVI an electroanatomic map of the LA was created to assess the presence of LVZ, defined by point measurements ≤0,5mV on the LA wall. Results General patient characteristics were 55% male gender, mean age 68 ± 9.8 years, median BMI 28 (IQR 26-31), median LVEF 60% (IQR 56-64), paroxysmal AF present in 38% of patients. LVZ was present in 37.9% patients during mapping (n=25). Patients were divided into LVZ positive (LVZ+) and LVZ negative (LVZ-) groups. LA volume (LAV) and LAV/BSA (LAVi) were higher in LVZ+ [145.3±32.7 ml and 75.6±17.9 ml/m² (n=25)] compared to LVZ- patients [120.8±31.7 ml and 58.1±14.8 ml/m² (n=41)], each p&amp;lt;0.05. LA-EAT volume (LA-EATV) and LA-EATV/BSA (LA-ETAVi) were higher in LVZ+ [64.2±23.5 ml and 33.0±11.3 ml/m² (n=20)] compared to LVZ- patients [52.7±16.7 ml and 25.2±7.8 ml/m² (n=38)], each p&amp;lt;0.05 (Figure 2a/b). A moderate correlation with the presence of LVZ is present for LAVi (r=0.47, p&amp;lt;0.001, n=66) and LA-EATVi (r=0.31, p=0.003, n=58). Both parameters are independent (r=0.194, p=0.145). A correlation with LVZ size can be described for LAVi (r=0.552, p&amp;lt;0.01) and LA-EATVi (r=0.303, p=0.05). A binomial logistic regression model using a combination of the two independent CMR-derived parameters LAVi and LA-EATVi (log odds (LVZ) = -6.691 + 0.054*LAVi + 0.086*LA-EATVi) was able to predict the presence of LVZ with an area under the ROC curve of 0.82 (p&amp;lt;0.001) and Nagelkerke's R² of 0.36 (Figure 2c). Overall accuracy in classification was 75.9% with a sensitivity of 55% and a specificity of 87%. Odds ratio for LAVi were 1.06 [1.02-1.10] and for LA-EATVi 1.09 [1.02-1.18]. Summary: This CMR-based combined prediction model utilizing LA volume and LA adipose tissue volume allows identification of low-risk patients for the presence of LA fibrosis.Figure 1:3D visualisation of structures

Long-term serial changes in left atrial volume and function after catheter ablation for atrial fibrillation

Abstract Background Catheter ablation for atrial fibrillation (AF) is an effective method to restore and maintain sinus rhythm. The value of left atrial (LA) volume and reservoir function at short-term after ablation have been shown to associate with clinical outcomes. However, data regarding serial changes in LA size and function after the ablation remain scarce. Purpose The purpose of this study was to investigate the serial changes in LA volume and function, and their relationship to the AF recurrence in patients who underwent primary ablation for AF and had preserved left ventricular ejection fraction (LVEF). Methods We retrospectively reviewed 1,204 patients (age: 72±10 years, male: 72%, LVEF: 62±4%, paroxysmal AF: 66%) for whom both pre- and post-procedural serial echocardiographic data were available. Echocardiography was performed at pre-, 1-year, 2-year and 3-year after the ablation procedure. The association between AF recurrence and changes in echocardiographic parameters were evaluated by A repeated measures ANOVA with a Greenhouse-Geisser correction and Bonferroni tests. The AF recurrence was defined as any documented atrial arrhythmia of &amp;gt; 30 seconds after a single ablation procedure. Results During the mean follow-up of 1725±713 days, AF recurrence was observed in 418 patients (34.7%) and persistent AF at last follow-up was 41 patients (3.4%). Patients with AF recurrence had significantly larger LA volume index (LAVI) and lower LA emptying fraction (LAEF) at baseline than those without (50.0±15.5 vs 41.4±14.4 mL/m2, P&amp;lt;0.001, and 31.2±14.9 vs 37.7±14.0 %, P&amp;lt;0.001, respectively) and these differences were maintained thereafter during the follow-up. The trend of LAVI decreased until 6 months later and then remained unchanged regardless of the AF recurrence. These trends were maintained in patients divided into initial paroxysmal and persistent AF. The trend of LAEF increased until 6 months later and then gradually decreased regardless of the AF recurrence. These trends were maintained in patients with persistent AF, however, LAEF continued to decline in patients with paroxysmal AF. (Figure) Conclusions The catheter ablation was associated with significant reduction in LAVI and improvement of LAEF in patients with persistent AF regardless of recurrent AF. In contrast, LAEF decreased gradually in patients with paroxysmal AF. These findings may suggest LA function in patients with AF declines gradually, even when they are maintained in sinus rhythm. However, both LAVI and LAEF in paroxysmal AF were better than persistent AF, suggesting that catheter ablation may be more effective in the paroxysmal AF stage.