Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Pulsed field ablation with the pentaspline catheter compared with cryoablation for the treatment of paroxysmal atrial fibrillation in the UK NHS: a cost-comparison analysis.

OBJECTIVES: Pulsed field ablation (PFA) is a promising new ablation modality for the treatment of atrial fibrillation (AF) that has recently become available in the UK National Health Service (NHS). We provide the first known economic evaluation of the technology. METHODS: A cost-comparison model was developed to compare the expected 12-month costs of treating AF using the pentaspline PFA catheter compared with cryoablation for a single hypothetical patient. Model parameters were based on a recent cost-effectiveness analysis by the National Institute for Health and Care Excellence where possible or published literature otherwise. Deterministic sensitivity, scenario and threshold analyses were conducted. RESULTS: Costs for a single patient treated with PFA were -3% (-£343) less over 12 months than those who received treatment with cryoablation. PFA was associated with 16% higher catheter costs but repeat ablation costs were over 50% less, driven by a reduction in repeat ablations required. Costs of managing complications were -£211 less in total for PFA compared with cryoablation. CONCLUSIONS: Routine adoption of PFA with the pentaspline PFA catheter looks to be as affordable for the NHS as current treatment alternative cryoablation.

Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease.

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).

Cryoablation Catheter Used in the Surgical Treatment of Atrial Fibrillation May Treat Chest Tube Pain: Engin Technique.

Postoperative pain after cardiac surgery plays an important role in the patient's recovery process. In particular, pain at the chest tube site can negatively affect the comfort and recovery of these patients. Effective pain control minimizes the risk of many complications. Oral and intravenous analgesics, epidural anesthesia, paravertebral block, and intercostal nerve blockade are used in chest tube pain control. We routinely use the surgical cryoablation method in the presence of atrial fibrillation in the preoperative period of cardiac surgery in our clinic. Here we aimed to describe our method of using the cryoablation catheter for intercostal nerve blockade.

Cryoneurolysis versus radiofrequency ablation outcome on pain experience in chronic low back pain (COPE): a single-blinded randomised controlled trial.

OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.

[Technical principles of ablation therapy]. / Technische Grundlagen der Ablationstherapie.

Catheter ablation is a standard procedure in modern cardiology. It can significantly improve the quality of life and life expectancy of cardiac arrhythmia patients. Besides cardiac mapping, ablation itself is a fundamental step to successfully treat cardiac arrhythmias. There are various ablation technologies at hand: In traditional radiofrequency (RF) ablation, electrical current flow generates coagulation necrosis. When understanding the biophysical principles of RF ablation, the investigator is capable to adapt lesion geometry and size to the requirements of the procedure and vary them individually. In addition, lesion metric indices evaluate and integrate important parameters such as power, duration, impedance and contact force to standardize and control RF lesions. Cryoablation induces ice crystals within myocardial tissue, which lead to destruction and electrical scarring of the treated tissue. Histologically, cryolesions are well-delineated with preserved tissue architecture and intact endocardium. Pulsed field ablation (PFA) is a novel rising technology, particularly used for pulmonary vein isolation. In contrast to classic thermal technologies (RF and cryoablation), PFA uses pulsed electrical fields to electroporate cardiac tissue and thereby creates damage on a cellular level only.

Impact of wall thickness on the tissue cooling effect of cryoballoon ablation.

AIMS: Understanding of the tissue cooling properties of cryoballoon ablation during pulmonary vein (PV) isolation is lacking. The purpose of this study was to delineate the depth of the tissue cooling effect during cryoballoon freezing at the pulmonary venous ostium. METHODS AND RESULTS: A left atrial-PV model was constructed using a three-dimensional printer with data from a patient to which porcine thigh muscle of various thicknesses could be affixed. The model was placed in a 37°C water tank with a PV water flow at a rate that mimicked biological blood flow. Cryofreezing at the PV ostium was performed five times each for sliced porcine thigh muscle of 2, 4, and 6 mm thickness, and sliced muscle cooling on the side opposite the balloon was monitored. The cooling effect was assessed using the average temperature of 12 evenly distributed thermocouples covering the roof region of the left superior PV. Tissue cooling effects were in the order of the 2, 4, and 6 mm thicknesses, with an average temperature of -41.4 ± 4.2°C for 2 mm, -33.0 ± 4.0°C for 4 mm, and 8.0 ± 8.7°C for 6 mm at 180 s (P for trend <0.0001). In addition, tissue temperature drops were steeper in thin muscle (maximum temperature drop per 5 s: 5.2 ± 0.9°C, 3.9 ± 0.7°C, and 1.3 ± 0.7°C, P for trend <0.0001). CONCLUSION: The cooling effect of cryoballoon freezing is weaker in the deeper layers. Cryoballoon ablation should be performed with consideration to myocardial thickness.

Cryocure-VT: the safety and effectiveness of ultra-low-temperature cryoablation of monomorphic ventricular tachycardia in patients with ischaemic and non-ischaemic cardiomyopathies.

AIMS: The ultra-low-temperature cryoablation (ULTC) ablation system using -196°C N2 cryogen has been reported to create lesions with freeze duration-dependent depth titratable to over 10 mm with minimum attenuation by scar. Cryocure-VT (NCT04893317) was a first-in-human clinical trial evaluating the safety and efficacy of a novel, purpose-built ULTC catheter in endocardial ablation of scar-dependent ventricular tachycardias (VTs). METHODS AND RESULTS: This prospective, multi-centre study enrolled patients referred for de novo or second ablations of recurrent monomorphic VT of both ischaemic and non-ischaemic aetiologies. Primary safety and efficacy endpoints of the study were freedom from device- or procedure-related major adverse events (MAEs) up to 30 days post-ablation, acute non-inducibility of clinical VTs at the end of the procedure, and freedom from sustained VT or implantable defibrillator intervention at 6 months. Ultra-low-temperature cryoablation was performed in 64 patients (age 67 ± 11 years, 78% ischaemic, ejection fraction = 35 ± 10%) at 9 centres. The primary acute effectiveness endpoint was achieved in 94% (51/54) of patients in whom post-ablation induction was attempted. There were no protocol-defined MAEs; four procedure-related serious adverse events resolved without clinical sequelae. At 6-month follow-up, 38 patients (60.3%) remained VT-free, and freedom from defibrillator shock was 81.0%, with no significant difference between ischaemic and non-ischaemic cohorts. In 47 patients with defibrillator for at least 6 months prior to the ablation, the VT burden was reduced from median of 4, inter-quartile range (IQR, 1-9) to 0, IQR (0-2). CONCLUSION: In this first-in-human multi-centre experience, endocardial ULTC ablation of monomorphic VT appears safe and effective in patients with both ischaemic-cardiomyopathy and non-ischaemic-cardiomyopathy. CLINICAL TRIAL REGISTRATION: NCT04893317.

[Cryobiopsies for the differentiation of interstitial pneumopathies]. / Kryobiopsien zur Differenzierung interstitieller Pneumopathien.

INTRODUCTION: Cryobiopsies for the differentiation of interstitial pneumopathies Abstract: Definitive diagnosis of interstitial pneumopathy is often difficult. In order to establish antifibrotic therapy, it is necessary to narrow down the aetiology and, in up to 40% of cases, obtain histological confirmation. The establishment of the endoscopic method of cryobiopsy achieves a diagnostic yield of 76-80% with significantly fewer complications compared to surgical lung biopsy.

Incidence of phrenic nerve injury during pulmonary vein isolation using different cryoballoons: data from a large prospective ablation registry.

AIMS: Phrenic nerve injury (PNI) is the most common complication during cryoballoon ablation. Currently, two cryoballoon systems are available, yet the difference is unclear. We sought to compare the acute procedural efficacy and safety of the two cryoballoons. METHODS: This prospective observational study consisted of 2,555 consecutive atrial fibrillation (AF) patients undergoing pulmonary vein isolation (PVI) using either conventional (Arctic Front Advance) (AFA-CB) or novel cryoballoons (POLARx) (POLARx-CB) at 19 centers between January 2022 and October 2023. RESULTS: Among 2,555 patients (68.8 ± 10.9 years, 1,740 men, paroxysmal AF[PAF] 1,670 patients), PVIs were performed by the AFA-CB and POLARx-CB in 1,358 and 1,197 patients, respectively. Touch-up ablation was required in 299(11.7%) patients. The touch-up rate was significantly lower for POLARx-CB than AFA-CB (9.5% vs. 13.6%, p = 0.002), especially for right inferior PVs (RIPVs). The touch-up rate was significantly lower for PAF than non-PAF (8.8% vs. 17.2%, P < 0.001) and was similar between the two cryoballoons in non-PAF patients. Right PNI occurred in 64(2.5%) patients and 22(0.9%) were symptomatic. It occurred during the right superior PV (RSPV) ablation in 39(1.5%) patients. The incidence was significantly higher for POLARx-CB than AFA-CB (3.8% vs. 1.3%, P < 0.001) as was the incidence of symptomatic PNI (1.7% vs. 0.1%, P < 0.001). The difference was significant during RSPV (2.5% vs. 0.7%, P < 0.001) but not RIPV ablation. The PNI recovered more quickly for the AFA-CB than POLARx-CB. CONCLUSIONS: Our study demonstrated a significantly higher incidence of right PNI and lower touch-up rate for the POLARx-CB than AFA-CB in the real-world clinical practice.

Breast cryoablation for the palliative treatment of indolent subtype of multicentric triple-negative breast cancer.

Breast cryoablation for palliative and curative treatment of breast cancer has been performed for decades. Although there is a recent resurgence of interest in breast cryoablation with curative intent for unifocal, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, this report highlights the essential role that cryoablation can play in the palliative treatment of multicentric oestrogen and progesterone receptor-negative and human epidermal growth factor receptor 2-negative (triple-negative) breast cancer, meeting the select pretreatment objectives such as breast or nipple pain relief and prevention of tumour erosion through the skin or nipple in patients who have failed or cannot tolerate the standard of care treatment.

Neoadjuvant in Situ and Systemic Immunotherapy with Lymph Node Cryoablation in Resectable Stage III Melanoma Metastasis: a Proof-of-Concept Study.

PURPOSE: Complete lymph node dissection is the recommended treatment for clinically detectable lymph nodes in stage III melanoma. This surgery is associated with substantial morbidity. We hypothesize that combining percutaneous imaging-guided cryoablation of locoregional lymph nodes metastases with neoadjuvant in situ and systemic immunotherapy could allow disease control and evaluate the feasibility of this combination in this proof-of-concept study. METHODS: We enrolled 15 patients with stage IIIB/IIIC melanoma. Patients were treated as follows: a single 240 mg flat dose infusion of nivolumab on day 1, cryoablation under local anesthesia using CT on day 2, and a single intralesional injection of 10-20 mg of ipilimumab into the lymphadenopathy treated by cryotherapy on day 3. Five-eight weeks after this procedure, complete lymph node dissection was performed according to routine care. The primary outcome measure of this study was feasibility, measured as the number of failures (i.e., inability to complete the entire procedure). RESULTS: The procedure was carried out successfully in 15 out of 15 patients with an observed number of failures of 0. The Bayesian analysis showed an estimated failure rate of 4.2% [0.2-20.6]. Eight patients (53%) had adverse events secondary to either immunotherapy or cryotherapy. Grade 3/4 events occurred in three patients, but all resolved quickly and patients could proceed to surgery as scheduled. Eight patients (53%) had a pathological complete or near complete response. CONCLUSION: Combining percutaneous cryotherapy with in situ ipilimumab and systemic nivolumab for stage III resectable melanoma is feasible with tolerable toxicity.

Safety and efficacy of the second-generation cryoballoon for left atrial appendage electrical isolation in canines.

AIMS: Left atrial appendage electrical isolation (LAAEI) has demonstrated a significant enhancement in the success rate of atrial fibrillation (AF) ablation. Nevertheless, concerns persist about the safety of LAAEI, particularly regarding alterations in left atrial appendage (LAA) flow velocity and the potential risks of thrombus. This study aimed to assess the efficacy and safety of LAAEI, investigating changes in LAA flow velocity in canines. METHODS AND RESULTS: The study comprised a total of 10 canines. The LAAEI procedure used by a 23 mm cryoballoon of the second generation was conducted at least 180 s. Intracardiac ultrasonography (ICE) was employed to quantify the velocity flow of the LAA both prior to and following LAAEI. Following a 3-month period, subsequent evaluations were performed to assess the LAA velocity flow and the potential reconnection. Histopathological examination was conducted. Left atrial appendage electrical isolation was effectively accomplished in all canines, resulting in a 100% acute success rate (10/10). The flow velocity in the LAA showed a notable reduction during LAAEI as compared with the values before the ablation procedure (53.12 ± 5.89 vs. 42.01 ± 9.22 cm/s, P = 0.007). After the follow-up, reconnection was observed in four canines, leading to a success rate of LAAEI of 60% (6/10). The flow velocity in the LAA was consistently lower (53.12 ± 5.89 vs. 44.33 ± 10.49 cm/s, P = 0.006), and no blood clot development was observed. The histopathological study indicated that there was consistent and complete injury to the LAA, affecting all layers of its wall. The injured tissue was subsequently replaced by fibrous tissue. CONCLUSION: The feasibility of using cryoballoon ablation for LAAEI was confirmed in canines, leading to a significant reduction of LAA flow velocity after ablation. Some restoration of LAA flow velocity after ablation may be linked to the passive movement of the LAA and potential reconnecting. However, this conclusion is limited to animal study; more clinical data are needed to further illustrate the safety and accessibility of LAAEI in humans.