Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

Association of use of Chinese herbal medicines and the risk of fracture in patients with osteoporosis: a population-based cohort study.

After utilizing a large population-based claims database and the application of propensity score match approach to reduce the confounding effects, we found that the use of Chinese herbal medicines (CHMs) was related to the lower risk of sequent osteoporotic fracture by 27% among the individuals with osteoporosis. The predominant effect was observed in those receiving CHMs for more than two years. INTRODUCTION: Osteoporosis (OS) is a highly disabling condition that can lead to fragility fracture, thus posing greater burdens of functional limitations for the affected individuals. It is unclear if the use of Chinese herbal medicines (CHMs) could reduce the risk of fracture due to OS. This study aimed to investigate the association of CHMs and the subsequent osteoporotic fracture risk among OS patients. METHODS: This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 250,699 newly diagnosed OS patients aged 20 years or older between 1998 and 2010. We recruited 103,325 CHM users following the onset of OS (CHM users) and randomly selected 103,325 subjects without CHM usage as controls (non-CHM users) by propensity score matching according to the demographic characteristics and comorbidities at enrollment. All enrollees were followed until the end of 2012 to record the incidence of osteoporotic fracture. We applied the Cox proportional hazard regression model to compute the hazard ratio (HR) of the risk of osteoporotic fracture. RESULTS: During the 15-year follow-up period, 7208 CHM users and 11,453 non-CHM users sustained osteoporotic fracture, with an incidence rate of 9.26 and 12.96, respectively, per 1000 person-years. We found that CHM users had a significantly reduced risk of osteoporotic fracture compared to non-CHM users (adjusted HR 0.73; 95% confidence interval [CI] = 0.70-0.75). Those treated with CHMs for longer than 730 days had a lower fracture risk by 54%. Some commonly used CHMs, such as Yan hu suo (Rhizoma Corydalis), Huang Qin (Scutellaria Baicale), Jie Geng (Platycodon grandifloras), Xiang Fu (Cyperus rotundus), Hai Piao Xiao (Cuttlebone Sepium), Jia-Wei-Xiao-Yao-San, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, and Du-Huo-Ji-Sheng-Tang, are related to the lower risk of fracture. CONCLUSIONS: The use of CHMs was associated with lower risk of osteoporotic fracture for OS patients, suggesting that it could be integrated into conventional therapy to prevent subsequent bone fracture.

Economic impact and cost-effectiveness of fracture liaison services: a systematic review of the literature.

Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023-$28,800 US dollars (USD) in Japan to $14,513-$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia.

OBJECTIVE: To investigate the association of different antipsychotic treatments with hospitalization due to self-harm among patients with schizophrenia. METHOD: This retrospective cohort study was based on Taiwan's universal health insurance database. Patients aged 15-45 years with a newly diagnosed schizophrenic disorder in 2001-2012 were included. The study outcome was the first hospitalization due to self-harm or undetermined injury after the diagnosis of schizophrenic disorders. The exposure status of antipsychotics was modeled as a time-dependent variable. The analyses were stratified by antipsychotic dosage based on defined daily dose (DDD). RESULTS: Among 70 380 patients with a follow-up of 500 355 person-years, 2272 self-harm hospitalization episodes were identified. Compared with none or former use, current use of several second-generation antipsychotics with a dose of one DDD or above, including amisulpride, aripiprazole, clozapine, risperidone, and sulpiride, was associated with decreased risk of self-harm hospitalization, with clozapine showing the strongest effect (adjusted rate ratio = 0.26, 95% confidence interval 0.15-0.47). CONCLUSION: The protective effect on self-harm may vary across different antipsychotics. Further studies are needed to replicate the findings.

Immune responses to Schistosoma haematobium infection.

Urogenital schistosomiasis is one of the greatest single infectious sources of human morbidity and mortality known. Through a complex cycle of infection, migration and eventual maturation and mating, S. haematobium (the aetiological agent of urogenital schistosomiasis) deposits highly immunogenic eggs within the bladder and other pelvic organs, activating a wide range of immune programs that determine both infection outcome as well as downstream immunopathology. In this review, we discuss the experimental and observational bases for our current understanding of these immune programs, focusing specifically on how the balance of type 1 and type 2 responses governs subsequent immunopathology and clinical outcome.

Autonomous robotic laparoscopic surgery for intestinal anastomosis.

Autonomous robotic surgery has the potential to provide efficacy, safety, and consistency independent of individual surgeon's skill and experience. Autonomous anastomosis is a challenging soft-tissue surgery task because it requires intricate imaging, tissue tracking, and surgical planning techniques, as well as a precise execution via highly adaptable control strategies often in unstructured and deformable environments. In the laparoscopic setting, such surgeries are even more challenging because of the need for high maneuverability and repeatability under motion and vision constraints. Here we describe an enhanced autonomous strategy for laparoscopic soft tissue surgery and demonstrate robotic laparoscopic small bowel anastomosis in phantom and in vivo intestinal tissues. This enhanced autonomous strategy allows the operator to select among autonomously generated surgical plans and the robot executes a wide range of tasks independently. We then use our enhanced autonomous strategy to perform in vivo autonomous robotic laparoscopic surgery for intestinal anastomosis on porcine models over a 1-week survival period. We compared the anastomosis quality criteria-including needle placement corrections, suture spacing, suture bite size, completion time, lumen patency, and leak pressure-of the developed autonomous system, manual laparoscopic surgery, and robot-assisted surgery (RAS). Data from a phantom model indicate that our system outperforms expert surgeons' manual technique and RAS technique in terms of consistency and accuracy. This was also replicated in the in vivo model. These results demonstrate that surgical robots exhibiting high levels of autonomy have the potential to improve consistency, patient outcomes, and access to a standard surgical technique.

Abnormal liver function test results are related to metabolic syndrome and BMI in Taiwanese adults without chronic hepatitis B or C.

BACKGROUND: Metabolic syndrome (MS) is considered a cause of abnormal deposition of fat into hepatocytes, which might be associated with hepatic steatosis or abnormal liver function. OBJECTIVE: The aim of this study was to explore the factors associated with MS and the relationship between MS and abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels in Taiwanese subjects without chronic hepatitis B (CHB) or C (CHC). SUBJECTS: We enrolled 2539 Taiwanese adults without CHB or CHC (age range: 16-88 years old) and investigated the factors related to MS using the NCEP-ATP (National Cholesterol Education Program-Adult Treatment Panel) III criteria; body mass index (BMI) was measured using Asia-Pacific criteria. RESULTS: The prevalence rate of MS in Taiwanese adults without CHB or CHC was 16.9% using the modified ATP III criteria and 15.4% using the International Diabetes Federation criteria. Males had a significantly higher prevalence rate than females (P<0.001), and subjects with MS were significantly older and had significantly higher BMI values and AST, ALT and GGT levels (all P<0.001). In univariate analyses, the abnormality of liver function test results were related to gender, level of fasting sugar, systolic blood pressure, triglyceride, high-density lipoprotein, BMI and MS (all P<0.05). Multivariate analysis showed that the male gender, a higher BMI value and MS were related to abnormal liver function test results. The cutoff value for ALT in relation to MS is 31 IU l(-1) for male and 18 IU l(-1) for female. CONCLUSION: The prevalence of MS in Taiwanese adults without hepatitis B or C was found to be high, and MS and BMI were identified as being related to abnormal liver function test results in these adults.

The reproducibility of the virtual organ computer-aided analysis program for evaluating 3-dimensional power Doppler ultrasonography of diffuse thyroid disorders.

AIM: The aim of this study was to evaluate the intra- observer and inter-observer reproducibility of 3-dimensional (3D) power Doppler ultrasonography with the virtual organ computer-aided analysis (VOCAL) program for measuring thyroid volume and vascular indices in patients with diffuse thyroid disorders. MATERIALS AND METHODS: Patients with diffuse goiters were examined by 3D ultrasonography from August 2005 to July 2006. The parameters for vascular assessment included the vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and thyroid size, and were obtained using the VOCAL program. This program used plane A and a 30 degrees rotational step. Intra-observer and inter-observer repeatability are presented as intra-class correlation coefficient (intra-CC) and inter-class correlation coefficient (inter-CC), with values >0.70 being acceptable. RESULTS: Sixty-three patients in total were enrolled for this study, including 19 patients with simple goiter and 44 patients with autoimmune thyroid disease (AITD) (23 Graves' disease, 21 Hashimoto's thyroiditis). Thyroid volume and 3 vascular indices showed excellent reproducibility in the AITD group (intra- CC>0.9373 and inter-CC>0.8763) and its subgroups. The VI had excellent consistent reproducibility in the simple goiter group (intra-CC>0.8987 and inter-CC>0.8881), but the other parameters did not. CONCLUSIONS: Based on this study, 3D power Doppler ultrasonography with the VOCAL program is a reliable tool for evaluating diffuse thyroid disorders due to an autoimmune process. The VI is the most reliable parameter.

Isoflurane attenuates dynorphin-induced cytotoxicity and downregulation of Bcl-2 expression in differentiated neuroblastoma SH-SY5Y cells.

BACKGROUND: It has been proposed that the volatile anesthetic isoflurane induces neuroprotection and that the endogenous opioid peptide dynorphin induces neurocytotoxicity in cells. The levels of dynorphin are often significantly elevated in neuropathophysiological conditions, and dynorphin can directly induce toxicity. However, the neuroprotective effects of isoflurane on dynorphin-induced cytotoxicity are still unclear. METHODS: In order to determine the effect of isoflurane on dynorphin-induced cytotoxicity in neuronal cells, we have designed a device wherein cultured human neuroblastoma SH-SY5Y cells can be exposed to isoflurane. Fully differentiated SH-SY5Y cells were obtained by treating the cells with retinoic acid for 6 days. We examined SH-SY5Y cell survival, apoptosis, and antiapoptotic protein expression by cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling stain, and Western blot analysis, respectively. RESULTS: After 16 h of dynorphin (10 microM) treatment, the SH-SY5Y cells showed significant cytotoxicity, apoptosis, and downregulation of the antiapoptotic Bcl-2 protein expression. These effects of dynorphin were significantly inhibited by isoflurane exposure for 32 h [pretreatment for 16 h and posttreatment (after dynorphin treatment) for 16 h]. CONCLUSION: Thus, our results suggest that isoflurane exerts neuroprotective effects in the case of dynorphin-induced pathophysiological disruption.

Semi-autonomous Robotic Anastomoses of Vaginal Cuffs Using Marker Enhanced 3D Imaging and Path Planning.

Autonomous robotic anastomosis has the potential to improve surgical outcomes by performing more consistent suture spacing and bite size compared to manual anastomosis. However, due to soft tissue's irregular shape and unpredictable deformation, performing autonomous robotic anastomosis without continuous tissue detection and three-dimensional path planning strategies remains a challenging task. In this paper, we present a novel three-dimensional path planning algorithm for Smart Tissue Autonomous Robot (STAR) to enable semi-autonomous robotic anastomosis on deformable tissue. The algorithm incorporates (i) continuous detection of 3D near infrared (NIR) markers manually placed on deformable tissue before the procedure, (ii) generating a uniform and consistent suture placement plan using 3D path planning methods based on the locations of the NIR markers, and (iii) updating the remaining suture plan after each completed stitch using a non-rigid registration technique to account for tissue deformation during anastomosis. We evaluate the path planning algorithm for accuracy and consistency by comparing the anastomosis of synthetic vaginal cuff tissue completed by STAR and a surgeon. Our test results indicate that STAR using the proposed method achieves 2.6 times better consistency in suture spacing and 2.4 times better consistency in suture bite sizes than the manual anastomosis.

Autonomous Laparoscopic Robotic Suturing with a Novel Actuated Suturing Tool and 3D Endoscope.

Compared to open surgical techniques, laparoscopic surgical methods aim to reduce the collateral tissue damage and hence decrease the patient recovery time. However, constraints imposed by the laparoscopic surgery, i.e. the operation of surgical tools in limited spaces, turn simple surgical tasks such as suturing into time-consuming and inconsistent tasks for surgeons. In this paper, we develop an autonomous laparoscopic robotic suturing system. More specific, we expand our smart tissue anastomosis robot (STAR) by developing i) a new 3D imaging endoscope, ii) a novel actuated laparoscopic suturing tool, and iii) a suture planning strategy for the autonomous suturing. We experimentally test the accuracy and consistency of our developed system and compare it to sutures performed manually by surgeons. Our test results on suture pads indicate that STAR can reach 2.9 times better consistency in suture spacing compared to manual method and also eliminate suture repositioning and adjustments. Moreover, the consistency of suture bite sizes obtained by STAR matches with those obtained by manual suturing.

Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia.

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.

Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families.

Evidence for association with schizophrenia has been reported for NOTCH4, although results have been inconsistent. Previous studies have focused on polymorphisms in the 5' promoter region and first exon of NOTCH4. Our aim was to test the association of the entire genomic region of NOTCH4 in 218 families with at least two siblings affected by schizophrenia in Taiwan. We genotyped seven single nucleotide polymorphisms (SNPs) of this gene, with average intermarker distances of 5.3 kb. Intermarker linkage disequilibrium (LD) was calculated using gold software, and single-locus and haplotype association analyses were performed using transmit software. We found that the T allele of SNP rs2071285 (P= 0.035) and the G allele of SNP rs204993 (P= 0.0097) were significantly preferentially transmitted to the affected individuals in the single-locus association analysis. The two SNPs were in high LD (D' > 0.8). Trend for overtransmission was shown for the T-G haplotype of the two SNPs to affected individuals (P= 0.053), with the A-A haplotype significantly undertransmitted (P= 0.034). The associated region distributed across the distal portion of the NOTCH4 gene and overlapped with the genomic region of the G-protein signaling modulator 3 and pre-B-cell leukemia transcription factor 2. In summary, we found modest association evidence between schizophrenia and the distal genomic region of NOTCH4 in this Taiwanese family sample. Further replication for association with the distal genomic region of NOTCH4 is warranted.

Anesthesia for patients with tracheal bronchus.

Tracheal bronchus is a congenital anatomical variant of patients with accessory bronchus in the right upper lobe deriving directly from the supracarinal trachea. Pre-operative consultation with the anesthesiologist is important for patient safety and can avoid adverse effects induced by endotracheal intubation. In this report, we described a case of tracheal bronchus in which general anesthesia was performed for video-assisted thoracoscopic surgery. We discussed some of the issues surrounding to complications in tracheal bronchus.

Caring Difficulties and Coping Strategies for Pediatric Organ Transplant Recipients and Their Families During Dark Recovery Experiences in the Hospital: Perspective of Health Professionals in Taiwan.

BACKGROUND: This study explored caring difficulties and the reliable coping strategies for pediatric organ transplant recipients (POTR) and their families during their dark recovery experiences (DRE) in the hospital from the perspectives of Taiwan organ transplant health professionals (OTHP) in Taiwan. METHODS: A qualitative design was used with a purposive sample of OT surgeons (OTS) and nurses. Data were collected by face-to-face in-depth interviews and analyzed by content analysis. RESULTS: Fifty-five subjects (39 females, 16 males) participated in this project. They included 15 OTS and 40 nurses. The nurses included registered nurses (n = 27), nurse practitioners (n = 5), and assistant or head nurses (n = 8). Their ages ranged from 25 to 66 (M = 38.4) years old. Thirty-eight (69%) had a college education and 17 (31%) had a graduate education. Their OT careers ranged from between 3 to 40 (M = 23.8) years for OTS, and 0.5 to 15 (M = 4.10) years for the OT nursing group. Six types of coping strategies for caring difficulties were reported: (a) implementing humanistic care training programs, (b) developing clinical paths for complex multiple OT cases, (c) holding case conferences for successful and failed cases, (d) developing OT expert training programs for interdisciplinary team members, (e) integrating acute and long-term care teams for difficult OT cases and families, and (f) inviting assistance from social workers. CONCLUSIONS: This research identifies important care difficulties and provides coping strategies that help to empower OTHP to care for POTR and their families during DRE, including increasing the manpower of experienced OT staff, conducting systematic in-service training, building teamwork between OTHP, and establishing a good pediatric OTHP team with consensus and good communication channels so as to effectively deal with the difficulties faced when caring for the POTR, and further to effectively enhance the overall quality of clinical care of POTR.

Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue.

Based on our previous finding of a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia, this study aimed to examine if hospitalization could affect expressions of these miRNAs. We compared their expression levels between acute state and partial remission state in people with schizophrenia (n=48) using quantitative PCR method. Further, to examine whether the blood and brain show similar expression patterns, the expressions of two miRNAs (hsa-miR-34a and hsa-miR-548d) were examined in the postmortem brain tissue of people with schizophrenia (n=25) and controls (n=27). The expression level of the seven miRNAs did not alter after ~2 months of hospitalization with significant improvement in clinical symptoms, suggesting the miRNAs could be traits rather than state-dependent markers. The aberrant expression seen in the blood of hsa-miR-34a and hsa-miR-548d were not present in the brain samples, but this does not discount the possibility that the peripheral miRNAs could be clinically useful biomarkers for schizophrenia. Unexpectedly, we found an age-dependent increase in hsa-miR-34a expressions in human cortical (Brodmann area 46 (BA46)) but not subcortical region (caudate putamen). The correlation between hsa-miR-34a expression level in BA46 and age was much stronger in the controls than in the cases, and the corresponding correlation in the blood was only seen in the cases. The association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia.

Initiation of atrial fibrillation by ectopic beats originating from the superior vena cava: electrophysiological characteristics and results of radiofrequency ablation.

BACKGROUND: The superior vena cava (SVC) has cardiac musculature extending from the right atrium. However, no previous study in humans has given details regarding the ectopic foci that initiate paroxysmal atrial fibrillation (PAF), which may originate from the SVC. METHODS AND RESULTS: A total of 130 patients with frequent attacks of PAF initiated by ectopic beats were included. Eight patients (6%) had spontaneous AF initiated by a burst of rapid ectopic beats from the SVC (located 19+/-7 mm above the junction of the SVC and right atrium), which was confirmed by multiplane angiographic and intracardiac echocardiographic visualization and was marked by a sharp SVC potential preceding atrial activity. During initial repetitive discharges, the group with SVC ectopy had a higher incidence of intravenous conduction block than the group with pulmonary vein ectopy (75% versus 37%; P=0.03). The activation time of the earliest intracardiac ectopic activities relative to ectopic P wave onset was significantly shorter in the SVC ectopy than the pulmonary vein ectopy group (37+/-15 versus 84+/-32 ms; P<0. 001). After 5+/-3 applications of radiofrequency energy, AF was eliminated. SVC angiography after ablation revealed a local indentation of the venous wall in one patient. Two patients manifested coexisting sinus rhythm and a "focal" fibrillating activity confined inside the SVC after radiofrequency ablation. During a follow-up period of 9+/-3 months, all 8 patients were free of antiarrhythmic drugs, without tachycardia recurrence or symptoms of SVC obstruction. CONCLUSIONS: Ectopic beats initiating PAF can originate from the SVC. A radiofrequency current delivered to eliminate these ectopies is a highly effective and safe way to prevent PAF.

Is 8-mm more effective than 4-mm tip electrode catheter for ablation of typical atrial flutter?

BACKGROUND: The prospective, randomized study comparing 4- with 8-mm tip electrodes for radiofrequency linear ablation of typical atrial flutter is not available. METHODS AND RESULTS: A total of 104 consecutive patients with typical atrial flutter were randomly assigned to undergo radiofrequency linear ablation using a 4- (Group I, n=54) or 8-mm tip electrode (Group II, n=50) catheter (temperature-control model, preset 70 degrees C). If complete bidirectional isthmus block could not be achieved after 5 pulses, the ablation catheter was changed to the other type; the maximal radiofrequency pulse number was limited to <10 pulses. Complete or incomplete isthmus conduction block was assessed by activation sequence in a multielectrode Halo catheter during low lateral right atrial and proximal coronary sinus pacing. Before shifting to the other catheter type, the 8-mm electrode catheter achieved higher complete isthmus block rate (92% versus 67%, P<0.05) with fewer pulses (2+/-1 versus 3+/-1, P<0.05), shorter procedure time (24+/-15 versus 31+/-12 minutes, P<0.05), and shorter fluoroscopic time (14+/-10 versus 23+/-15 minutes, P<0.05). After 5 failed ablation pulses, 12 (67%) of 18 patients in group I attained complete isthmus block by using an 8-mm tip catheter, but none of 4 patients in group II achieved complete block by changing to a 4-mm tip catheter. CONCLUSIONS: The 8-mm tip electrodes are more effective than the standard 4-mm length electrodes in linear ablation for typical atrial flutter. This clinical benefit may be of particular value for some patients with broad and/or thick isthmus.

Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation.

BACKGROUND: Atrial fibrillation (AF) can be initiated by ectopic beats originating from the atrial or great venous tissues. This study investigated the anatomic characteristics and electrophysiological properties of pulmonary veins (PVs), as well as the possible mechanisms and response to drugs of ectopic foci, and assessed the effects of radiofrequency (RF) ablation on AF initiated by ectopic beats originating from PVs. METHODS AND RESULTS: Seventy-nine patients with frequent episodes of paroxysmal AF and 10 control patients were included. Distal PVs showed the shortest effective refractory periods (ERPs), and right superior PVs showed a higher incidence of intra-PV conduction block than left superior PVs. Superior and left PVs had longer myocardial sleeves than inferior and right PVs, respectively. These electrophysiological characteristics were similar between AF and control patients. Propranolol, verapamil, and procainamide suppressed ectopic beats that originated from the PVs. Of 116 ectopic foci that initiated AF, 103 (88.8%) originated from PVs. A mean of 7+/-3 RF applications completely eliminated 110 ectopic foci (94.8%). During the 6+/-2-month follow-up period, 68 patients (86. 1%) were free of AF without any antiarrhythmic drugs. Follow-up transesophageal echocardiogram showed 42.4% of ablated PVs had focal stenosis. One patient had mild exertional dyspnea after ablation, but it resolved 3 months later; 1 patient had onset of mild exertional dyspnea 5 months after ablation. CONCLUSIONS: Electrophysiological characteristics of PVs are different from those in the atria. Ectopic beats from PVs can initiate AF, and beta-adrenergic receptor blocker, calcium channel blockers, and sodium channel blockers can suppress these ectopic beats. Careful mapping and elimination of these ectopic foci can cure paroxysmal AF.

Alterations of heart rate variability after radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins.

BACKGROUND: Transient sinus bradycardia and hypotension have been reported as complications during radiofrequency (RF) ablation of focal atrial fibrillation (AF) originating from pulmonary veins (PVs). This study used heart rate variability (HRV) to evaluate the effects of focal PVs ablation on autonomic function. METHODS AND RESULTS: Thirty-seven patients with paroxysmal AF were referred for ablation. The study group included 30 patients who underwent transseptal ablation of PVs, and the control group included 7 patients who underwent the transseptal procedure without ablation. The mean sinus rate and time-domain (standard deviation of RR intervals and root-mean-square of differences of adjacent RR intervals) and frequency-domain (low frequency, high frequency, and low-frequency/high-frequency ratio) analyses of HRV were obtained by use of 24-hour Holter monitoring before and 1 week, 1 month, and 6 months after ablation. All the triggering points of AF were from PVs, and they were successfully ablated. Severe bradycardia and hypotension were noted during ablation of PVs in 6 patients (group IA); 24 patients without the above complication belonged to group IB. Compared with preablation values, a significant increase in mean sinus rate and low-frequency/high-frequency ratio and a significant decrease in standard deviation of RR intervals, root-mean-square of differences of adjacent RR intervals, low frequency, and high frequency were noted in groups IA and IB patients 1 week after ablation. The changes in HR and HRV recovered spontaneously in the 2 subgroups by 1 month later. These parameters of HRV did not change in the control group after the transseptal procedure. CONCLUSIONS: Transient autonomic dysfunction with alterations in HR and HRV occurred after ablation of focal AF originating from PVs.