Real-World Data of Radiofrequency Catheter Ablation in Paroxysmal Atrial Fibrillation: Short- and Long-term Clinical Outcomes from the Prospective Multicenter REAL-AF Registry.

BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: We aim to assess the contemporary real-world practice approach and long-term outcomes of RF-CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; NCT04088071) registry, patients undergoing RF-CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2,470 patients undergoing CA of registry from January 2018 to December 2022 were included. The mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedure and total RF times of 95.4±41.7 and 22.1±11.8 min, respectively. At one-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing PVI vs. PVI+ ablation approaches. The complication rate was 1.9%. CONCLUSIONS: Refinement of RF-CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows, resulted in excellent short and long-term clinical outcomes.

A prospective multi-site registry of real-world experience of catheter ablation for treatment of symptomatic paroxysmal and persistent atrial fibrillation (Real-AF): design and objectives.

PURPOSE: Catheter ablation has become a mainstay therapy for atrial fibrillation (AF) with rapid innovation over the past decade. Variability in ablation techniques may impact efficiency, safety, and efficacy; and the ideal strategy is unknown. Real-world evidence assessing the impact of procedural variations across multiple operators may provide insight into these questions. The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (PAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that will enroll patients at high volume centers, including academic institutions and private practices, with operators performing ablations primarily with low fluoroscopy when possible. The study will also evaluate the contribution of advent in technologies and workflows to real-world clinical outcomes. METHODS: Patients presenting at participating centers are screened for enrollment. Data are collected at the time of procedure, 10-12 weeks, and 12 months post procedure and include patient and detailed procedural characteristics, with short and long-term outcomes. Arrhythmia recurrences are monitored through standard of care practice which includes continuous rhythm monitoring at 6 and 12 months, event monitors as needed for routine care or symptoms suggestive of recurrence, EKG performed at every visit, and interrogation of implanted device or ILR when applicable. RESULTS: Enrollment began in January 2018 with a single site. Additional sites began enrollment in October 2019. Through May 2021, 1,243 patients underwent 1,269 procedures at 13 institutions. Our goal is to enroll 4000 patients. DISCUSSION: Real-AF's multiple data sources and detailed procedural information, emphasis on high volume operators, inclusion of low fluoroscopy operators, and use of rigorous standardized follow-up methodology allow systematic documentation of clinical outcomes associated with changes in ablation workflow and technologies over time. Timely data sharing may enable real-time quality improvements in patient care and delivery. Trial registration Clinicaltrials.gov: NCT04088071 (registration date: September 12, 2019).

Administration of high titer convalescent anti-SARS-CoV-2 plasma: From donor selection to monitoring recipient outcomes.

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.

Advanced head and neck surgery training during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has significantly impacted medical training. Here we assess its effect on head and neck surgical education. METHODS: Surveys were sent to current accredited program directors and trainees to assess the impact of COVID-19 on the fellow's experience and employment search. Current fellows' operative logs were compared with those of the 2018 to 2019 graduates. RESULTS: Despite reduction in operative volume, 82% of current American Head and Neck Society fellows have reached the number of major surgical operations to support certification. When surveyed, 86% of program directors deemed their fellow ready to enter practice. The majority of fellows felt prepared to practice ablative (96%), and microvascular surgery (73%), and 57% have secured employment to follow graduation. Five (10%) had a pending job position put on hold due to the pandemic. CONCLUSIONS: Despite the impact of the COVID-19 pandemic, current accredited trainees remain well-positioned to obtain proficiency and enter the work-force.

Phase contrast time-lapse microscopy datasets with automated and manual cell tracking annotations.

Phase contrast time-lapse microscopy is a non-destructive technique that generates large volumes of image-based information to quantify the behaviour of individual cells or cell populations. To guide the development of algorithms for computer-aided cell tracking and analysis, 48 time-lapse image sequences, each spanning approximately 3.5 days, were generated with accompanying ground truths for C2C12 myoblast cells cultured under 4 different media conditions, including with fibroblast growth factor 2 (FGF2), bone morphogenetic protein 2 (BMP2), FGF2 + BMP2, and control (no growth factor). The ground truths generated contain information for tracking at least 3 parent cells and their descendants within these datasets and were validated using a two-tier system of manual curation. This comprehensive, validated dataset will be useful in advancing the development of computer-aided cell tracking algorithms and function as a benchmark, providing an invaluable opportunity to deepen our understanding of individual and population-based cell dynamics for biomedical research.

Population-level predictors of persistent hyperparathyroidism.

BACKGROUND: Systematic study of outcomes of initial surgery for primary hyperparathyroidism (PHPT) has been limited by selection and self-reporting biases. To avoid these biases, we evaluated parathyroidectomy (PTx) outcomes within an integrated health care system encompassing 3.25 million enrollees. METHODS: All patients undergoing PTx for PHPT from 1995 to 2010 were studied. Persistent and recurrent disease were defined by a serum calcium level >10.5 mg/dL before or after 6 months postoperatively, respectively. The effect of demographic, clinical, and hospital volume-related variables was assessed by the use of multivariate logistic regression. RESULTS: A total of 1,190 initial operations for PHPT were performed at 14 hospitals. Follow-up calcium levels were available in 97% of subjects. The overall success rate was 92%, and 5% of patients developed recurrent disease. Age ≥ 70 years was predictive of persistent disease (odds ratio 1.80, P < .05). High-volume hospital (>100 cases) predicted against persistent disease (odds ratio 0.42, P < .05) and carried 96% success rate. Negative or equivocal sestamibi scan was associated with a lower success rate (success rate 89% vs 95% for positive scan, P < .05). Reoperation was performed in 12% of patients with persistent or recurrent PHPT. CONCLUSION: The success rate of PTx is influenced by patient age, hospital volume, and sestamibi scan result. Surgical outcomes may be optimized by designating high-volume centers in the community setting.

Solitary spinal metastasis of Hürthle cell thyroid carcinoma.

Hürthle cell carcinoma is a rare variant of differentiated thyroid cancer that occasionally forms distant metastases. However, even in the presence of metastases, patients with Hürthle cell carcinoma have a relatively good prognosis. There are few reports of Hürthle cell carcinoma metastases to the vertebral column, and none describing aggressive resection of spinal metastases. Here, we report a 68-year-old woman with a solitary metastasis of Hürthle cell carcinoma to the T1 vertebral body causing severe kyphotic deformity, myelopathy, and pain. The patient was treated with aggressive excisional decompression of the spinal cord and T1 vertebral body resection from an entirely posterior approach. Reconstruction and stabilization of the anterior spine was accomplished with a transforaminal lumbar interbody fusion allograft spacer and posterior instrumentation. We discuss aspects of the diagnosis, management, patient selection, and surgical treatment of metastatic Hürthle cell carcinoma in reference to the literature.

CD20 positive mycosis fungoides: a case report.

CD20 positive T-cell lymphoma is extremely rare. Most reported cases are nodal peripheral T-cell lymphomas (PTCLs) or rarely lymphoma involving extranodal sites. Only two cases of CD20 positive T-cell lymphomas involving the skin have been previously reported and were classified as PTCL - not otherwise specified. We present a case report of a 53-year-old man with CD20 positive mycosis fungoides (MF) involving the skin and an inguinal lymph node. The patient presented with erythematous patches and plaques of the right lower extremity and was found to have an enlarged inguinal lymph node 2 years later. Flow cytometric immunophenotyping of the lymph node aspirate showed a CD2+/CD3+/CD4+/CD5+/CD7-/CD8- T-cell population with CD20 co-expression. Molecular studies by polymerase chain reaction demonstrated clonal T-cell receptor gamma chain gene rearrangement. Immunoglobulin heavy and light chain gene rearrangements were not identified. To our knowledge, this is the first case of CD20 positive MF involving a lymph node to be reported in the literature.

Nonatherosclerotic pathology of the neck vessels: prevalence and flow patterns.

OBJECTIVES: To determine the prevalence and flow characteristics of nonatherosclerotic pathologies of the cervical vessels. DESIGN: From 1997 to 2003, 11 480 ultrasound tests were performed for neck vessel evaluation on patients with cerebrovascular symptoms and trauma, and on asymptomatic patients with a bruit, cervical mass, or prior to aortocoronary bypass. When necessary, these findings were confirmed by other imaging modalities. RESULTS: A total of 3010 repeated tests were excluded, leaving 8470 patients. The prevalence of nonatherosclerotic pathologies (n = 55) was 0.65%. The most common was thromboembolism (n = 19, 0.22%), followed by dissection (n = 16, 0.19%), carotid body tumors (n = 5, 0.06%), aneurysms (n = 4, 0.05%), fibromuscular dysplasia (n = 4, 0.05%), Takayasu's arteritis (n = 1, 0.01%), pseudoaneurysms (n = 5, 0.06%), and arteriovenous fistulae (n = 1, 0.01%). Cerebrovascular symptoms were present in 27 patients (49%). CONCLUSION: Nonatherosclerotic pathology accounts for 0.65% of patients referred for neck vessel evaluation. About half of them are symptomatic. Diagnosis of these pathologies and knowledge of their flow characteristics is important for patient management.

Primary Ewing sarcoma/PNET of the kidney: fine-needle aspiration, histology, and dual color break apart FISH Assay.

A 34-year-old previously healthy Hispanic man presented with lower back pain. CT scan revealed an 8-cm space-occupying lesion in the superior pole of the left kidney with numerous small lytic lesions in the skull, vertebrae, ribs, and pelvic bones. CT-guided fine-needle aspiration biopsy revealed a high-grade primitive small round cell tumor with the tumor cells being strongly positive for CD99 and vimentin. The patient subsequently underwent a left nephrectomy. Fluorescence in situ hybridization analysis using a DNA probe for the Ewing Sarcoma breakpoint region 1 (EWSR1) on chromosome 22g12 revealed a rearrangement of the EWSR1 locus. The diagnosis of primary Ewing sarcoma/primitive neuroectodermal tumor of the kidney was established.

Validation and clinical application of time-frequency analysis of atrial fibrillation electrocardiograms.

INTRODUCTION: Fibrillatory rates can reliably be obtained from surface ECGs during atrial fibrillation (AF) and correspond with right atrial (RA) and coronary sinus (CS) rates, while both the relation with pulmonary venous (PV) rates and determinants of fibrillatory waveform are unknown. Class III antiarrhythmic drugs prolong atrial refractoriness and decrease its dispersion, effects that may be reflected in ECG parameters. Consequently, this study sought (1) to investigate the relation between ECG fibrillatory rate and waveform characteristics with intraatrial/PV fibrillatory activity and (2) to noninvasively monitor class III antiarrhythmic drug effects in patients with AF. METHODS AND RESULTS: Thirty-six patients with drug-refractory AF who underwent catheter-based pulmonary vein isolation and had AF at the beginning of the procedure were studied. A positive correlation between V1 rates obtained by time-frequency analysis and RA (R = 0.97, P < 0.001), CS (R = .71, P < 0.001), and PV rates (R = 0.65, P = 0.001) was found. Exponential decay defined as decay of the curve that connects power maxima of dominant and harmonic frequency components correlated with RA rate dispersion (R = 0.53, P = 0.004). In amiodarone-treated patients (n = 7), V1 rate (286 +/- 64 vs. 371 +/- 40 fpm, P < 0.001) and exponential decay (1.06 +/- 0.29 vs. 1.38 +/- 0.38, P = 0.034) were lower than in patients without amiodarone (n = 29). In 19 additional patients with persistent AF, oral dofetilide treatment decreased mean fibrillatory rate from 377 +/- 57 to 294 +/- 50 fpm (P < 0.001) and exponential decay from 1.24 +/- 0.43 to 0.85 +/- 0.22 (P = 0.002). CONCLUSIONS: Fibrillatory waves of surface ECG lead V1 closely reflect right atrial, and, to a lesser degree, left atrial activity. Time-frequency analysis allows noninvasive monitoring of antiarrhythmic drug effects on fibrillatory rate and waveform.

Effects of the components of hormone therapy on matrix metalloproteinases in breast-cancer cells: an in vitro study.

A combination of E and progestogens significantly increased matrix metalloproteinase (MMP)-2 in both T47D cells (E(2)-medroxyprogesteroneacetate [MPA] and E(2)-P) and MCF-7 cells (E(2)-MPA, E(2)-P, and equilin-MPA). All combinations resulted in higher MMP-9 levels in MCF-7 cells, but higher MMP-9 levels resulted only with equilin-norethinderone in T47D cells.

Hemodynamic effects of intermittent pneumatic compression in patients with critical limb ischemia.

BACKGROUND: Traditional teaching assumes that the distal arterial tree is maximally dilated in patients with critical limb ischemia (CLI). Endovascular or arterial bypass procedures are the commonly used interventions to increase distal perfusion. However, other forms of treatment such as spinal cord stimulation or intermittent pneumatic compression (IPC) have been shown to improve limb salvage rates. This prospective study was designed to determine if the use of IPC increases popliteal, gastrocnemial, collateral arterial, and skin blood flow in patients with CLI. METHODS: Twenty limbs with CLI in 20 patients (mean age, 74 years) were evaluated with duplex ultrasound scans and laser Doppler fluxmetry in the semi-erect position before, during, and after IPC. One pneumatic cuff was applied on the foot and the other on the calf. The maximum inflation pressure was 120 mm Hg and was applied for 3 seconds at three cycles per minute. All patients had at least two-level disease by arteriography. Fourteen limbs were characterized as inoperable, and six were considered marginal for reconstruction. Flow volumes were measured in the popliteal, medial gastrocnemial, and a genicular collateral artery. Skin blood flux was measured on the dorsum of the foot at the same time. RESULTS: Significant flow increase during the application of IPC was found in all three arteries (18/20 limbs) compared with baseline values (P < .02). The highest change was seen in the popliteal, followed by the gastrocnemial and the collateral artery. After the cessation of IPC, the flow returned to baseline. This was attributed to the elevation of time average velocity, as the diameter of the arteries remained unchanged. The skin blood flux increased significantly as well (P < .03). In the two limbs without an increase in the arterial or skin blood flow, significant popliteal vein reflux was found. Both limbs were amputated shortly after. CONCLUSIONS: IPC increases axial, muscular, collateral, and skin blood flow in patients with CLI and may be beneficial to those who are not candidates for revascularization. Patients with significant venous reflux may not benefit from IPC. This supports the theory that one of the mechanisms by which IPC enhances flow is by increasing the arteriovenous pressure gradient.

Study of the venous reflux progression.

BACKGROUND: Patients with chronic venous disease (CVD) often ask whether elective vein surgery could be delayed without consequences. Because the natural history of CVD is not well known, this study was designed to determine its progression in such patients. METHODS: One hundred and sixteen limbs in 90 patients who had at least 2 exams with duplex ultrasound (DU) scanning prior to vein surgery at a university medical center were studied. These were patients who were offered an operation but for various reasons were treated at a later stage. Patients were classified by the CEAP system. RESULTS: The mean age of the patients was 49 years (range, 23 to 81 years). A second DU scan was performed 1 to 43 months after the initial exam (median, 19 months). Eighty-five limbs (73.3%) were unchanged. Thirteen limbs (11.2%) had progression of clinical stage, and seven had progression on DU scanning as well. Seven limbs progressed from C2 to C3, four limbs from C3 to C4, and two limbs from C4 to C6. Thirty-four limbs had a documented change on repeat DU scanning. In 3 of these limbs, reflux was missed on the initial exam; therefore, 31 limbs had progression of disease. The great saphenous vein and tributaries were the most often anatomic sites affected by a change, followed by perforators. Seventeen limbs (14.7%) had extension of pre-existing reflux, and 14 (12.1%) had reflux in a new segment. In 11 of these limbs, a change in the initial plan for treatment was required. Symptomatic or DU changes were noted 6 months or later in 95% of limbs and 74.2% of limbs with disease progression were diagnosed at 12 months or later. All but one of the 13 symptomatic limbs developed symptoms at least a year later. CONCLUSION: Nearly one third of patients with venous reflux had progression. Anatomic extension is frequent with disease progression but not a pre-requisite. Progression was found in most limbs 6 months after the initial study. Patients undergoing treatment for their veins may need another DU exam if this time interval is exceeded.

Determinants and prognostic significance of immediate atrial fibrillation recurrence following cardioversion in patients undergoing pulmonary vein isolation.

BACKGROUND: Immediate recurrence of atrial fibrillation (IRAF) occurs frequently after electrical cardioversion, its electrophysiological determinants and prognostic significance have, however, not been studied in detail. This study aimed to explore (1) the association of IRAF with clinical characteristics, pulmonary vein (PV) arrhythmogenicity as well as atrial electrophysiologic properties and (2) the prognostic significance of IRAF for outcome of PV isolation for atrial fibrillation (AF). METHODS AND RESULTS: The subjects of this study were 41 consecutive patients (30 males, 11 females) who underwent PV isolation for drug-refractory AF. Following successful initial cardioversion, 19 patients (46%) had IRAF within 2 minutes. Coupling intervals of AF reinitiating beats arising from PVs were shorter (386 +/- 39 vs 490 +/- 136 ms, P = 0.008) and prematurity indices (0.38 +/- 0.06 vs 0.51 +/- 0.12, P = 0.01) smaller than those of premature beats not initiating AF. Patients with IRAF had more frequently AF duration <1 month, a longer P-wave duration, and a longer mid coronary sinus AF cycle length. Multivariate regression analysis revealed coronary sinus AF cycle length (beta= 0.186, P = 0.049), which was closely correlated with conduction time along the coronary sinus (R = 0.716, P = 0.003) to be independently associated with IRAF. While early AF recurrence rate (within the first 5 days) following the procedure was higher in the IRAF group (53 vs 18%, P = 0.02), outcome was not different between the two groups thereafter. CONCLUSIONS: (1) IRAF is common in patients undergoing PV isolation for AF, (2) is initiated by premature atrial beats with short coupling intervals, and (3) seems to be associated with conduction disturbances along the coronary sinus. It reflects susceptibility of arrhythmia recurrence within the first 5 days after the procedure, but not thereafter.

Heat shock protein 27 is expressed in normal and malignant human melanocytes in vivo.

BACKGROUND: Heat shock proteins (HSPs) are a family of highly conserved proteins found ubiquitously in mammalian cells, believed to be regulators of normal cell physiology and the cellular stress response. In addition, the small 27-kDa heat shock protein (HSP27) has previously been found to be a differentiation marker for keratinocytes and a prognostic marker associated with increased survival in certain cancerous tumors. METHODS: Using immunohistochemistry on routinely processed paraffin sections, we examined skin biopsies from 15 invasive melanomas, 13 intradermal nevi, and two compound nevi immunostained with a mouse monoclonal antibody to HSP27. In addition, cultured melanocytes were heat stressed at 45 degrees C for 1 h and then fixed and immunostained in order to localize HSP27 expression intracellularly. RESULTS: We found cytoplasmic and strong perinuclear staining of HSP27 in melanocytes in normal skin, in melanomas, and in nevi. Nuclear reactivity was absent. In addition, in cultured non-malignant melanocytes, HSP27 expression relocated from the cytoplasm to the nucleus with heat stress. CONCLUSIONS: To our knowledge, this investigation is the first to demonstrate that HSP27 is expressed in melanocytes in normal skin, in nevi, and in non-malignant cultured melanocytes.

Effectiveness of catheter ablation for coexisting atrial fibrillation and atrial flutter.

In 79 consecutive patients (51 men and 28 women) with paroxysmal (n = 54) or persistent atrial fibrillation (AF) (n = 25) and typical, isthmus-dependent atrial flutter (AFl), pulmonary vein (PV) isolation and anatomically guided linear ablation of the right atrial isthmus was performed during the same procedure. After 208 +/- 331 days of follow-up, 42% remained free of AF and AFl, and a symptomatic lessening was reported by 77%. Paroxysmal AF (beta = 1.682, p = 0.008) and ablation of 3 or 4 PVs (beta = 1.830, p = 0.013) were independent predictors for arrhythmia-free survival. Combined catheter ablation of PVs and the right atrial isthmus for the treatment of patients with mixed AF and AFl is moderately effective in preventing early arrhythmia recurrence but leads to clinical improvement in most patients.