Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection.

Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). Vaccines were administered by intramuscular injection followed by electroporation at study entry and at weeks 4, 12, and 24. HCV-specific CD4+ and CD8+ T-cell immune responses were measured by IFNγ ELISpot and flow cytometry-based assays. Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia. PREVENTION RELEVANCE: The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses.

Phylotypic Diversity of Bacteria Associated with Speleothems of a Silicate Cave in a Guiana Shield Tepui.

The diversity of microorganisms associated with speleological sources has mainly been studied in limestone caves, while studies in silicate caves are still under development. Here, we profiled the microbial diversity of opal speleothems from a silicate cave in Guiana Highlands. Bulk DNAs were extracted from three speleothems of two types, i.e., one soft whitish mushroom-like speleothem and two hard blackish coral-like speleothems. The extracted DNAs were amplified for sequencing the V3-V4 region of the bacterial 16S rRNA gene by MiSeq. A total of 210,309 valid reads were obtained and clustered into 3184 phylotypes or operational taxonomic units (OTUs). The OTUs from the soft whitish speleothem were mostly affiliated with Acidobacteriota, Pseudomonadota (formerly, Proteobacteria), and Chloroflexota, with the OTUs ascribed to Nitrospirota being found specifically in this speleothem. The OTUs from the hard blackish speleothems were similar to each other and were mostly affiliated with Pseudomonadota, Acidobacteriota, and Actinomycetota (formerly, Actinobacteria). These OTU compositions were generally consistent with those reported for limestone and silicate caves. The OTUs were further used to infer metabolic features by using the PICRUSt bioinformatic tool, and membrane transport and amino acid metabolism were noticeably featured. These and other featured metabolisms may influence the pH microenvironment and, consequently, the formation, weathering, and re-deposition of silicate speleothems.

Association between hypertension and cutaneous melanoma, and the effect of aspirin: extended follow-up of a large randomised controlled trial.

BACKGROUND: The association between hypertension and melanoma is unclear, and previous analyses of data from the ASPirin in Reducing Events in the Elderly (ASPREE) study demonstrated a reduced number of invasive melanoma events amongst aspirin-exposed hypertensive individuals. METHODS: Data from the ASPREE study which included (1) the intervention period with a median follow-up of 4.7 years, and (2) the observational period with an additional 2 years follow-up, were combined for this analysis. Logistic regression analyses examined the association between baseline hypertension and treatment status and past melanoma history. Survival analyses examined the association between hypertension and melanoma risk, and the effect of aspirin across hypertension groups. Cox proportional hazards models were used to compare incidence across groups. RESULTS: 19,114 participants (median age of 74 years) were randomised to daily 100 mg aspirin or placebo. At baseline, hypertension and past melanoma history were recorded in 14,195 and 685 individuals, respectively. After adjustment for confounders, hypertension was significantly associated with past melanoma history (OR=1.34, 95%CI: 1.11-1.62). In a prospective analysis, baseline hypertension was not associated with melanoma risk. However, aspirin was associated with a reduced risk of incident melanoma amongst individuals with uncontrolled hypertension (blood pressure ≥140/90 mmHg; HR=0.63, 95%CI 0.44-0.89), but not in those with controlled hypertension (HR=1.04, 95%CI 0.74-1.46). CONCLUSION: Our results support a reduced melanoma incidence amongst individuals with uncontrolled hypertension exposed to aspirin. Additional studies are required to confirm these findings.

Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial.

The effects of aspirin on melanoma are unclear, with studies reporting conflicting results. Data from two periods of the ASPirin in Reducing Events in the Elderly (ASPREE) study; the randomized placebo-controlled trial period examining daily 100 mg aspirin in older adults with a median follow-up of 4.7 years, and the second period, an additional 2 years of observational follow-up, were utilized in this secondary analysis to examine whether aspirin exposure is associated with a reduced cutaneous melanoma incidence. All melanoma cases were adjudicated and Cox proportional hazards models were used to compare incidence between randomized treatment groups. ASPREE recruited 19,114 participants with a median age of 74 years. During the trial period, 170 individuals (76 aspirin, 94 placebo) developed an invasive melanoma, and no significant effect of aspirin was observed on incident melanoma [HR = 0.81; 95% confidence interval (CI), 0.60-1.10]. Including the additional 2 years of observational follow-up (median follow-up of 6.3 years), 268 individuals (119 aspirin, 149 placebo) developed an invasive melanoma, and similar results were observed (HR = 0.81; 95% CI, 0.63-1.03). A reduced number of events was observed with aspirin among females in a subgroup analysis (HR = 0.65; 95% CI, 0.44-0.92); however, the interaction effect with males (HR = 0.92; 95% CI, 0.68-1.25) was nonsignificant (P = 0.17). Our findings from this randomized trial do not provide strong support that aspirin is associated with a reduced risk of invasive melanoma in older individuals. Additional studies are required to further explore this relationship. PREVENTION RELEVANCE: Melanoma prevention is an important strategy to improve outcomes and while preventive efforts have largely focused on sun protection, the role of potential chemopreventive agents such as aspirin warrants investigation.

Examination of Intersectionality and the Pipeline for Black Academic Surgeons.

IMPORTANCE: The lack of underrepresented in medicine physicians within US academic surgery continues, with Black surgeons representing a disproportionately low number. OBJECTIVE: To evaluate the trend of general surgery residency application, matriculation, and graduation rates for Black trainees compared with their racial and ethnic counterparts over time. DESIGN, SETTING, AND PARTICIPANTS: In this nationwide multicenter study, data from the Electronic Residency Application Service (ERAS) for the general surgery residency match and Graduate Medical Education (GME) surveys of graduating general surgery residents were retrospectively reviewed and stratified by race, ethnicity, and sex. Analyses consisted of descriptive statistics, time series plots, and simple linear regression for the rate of change over time. Medical students and general surgery residency trainees of Asian, Black, Hispanic or Latino of Spanish origin, White, and other races were included. Data for non-US citizens or nonpermanent residents were excluded. Data were collected from 2005 to 2018, and data were analyzed in March 2021. MAIN OUTCOMES AND MEASURES: Primary outcomes included the rates of application, matriculation, and graduation from general surgery residency programs. RESULTS: Over the study period, there were 71 687 applicants, 26 237 first-year matriculants, and 24 893 graduates. Of 71 687 applicants, 24 618 (34.3%) were women, 16 602 (23.2%) were Asian, 5968 (8.3%) were Black, 2455 (3.4%) were Latino, and 31 197 (43.5%) were White. Women applicants and graduates increased from 29.4% (1178 of 4003) to 37.1% (2293 of 6181) and 23.5% (463 of 1967) to 33.5% (719 of 2147), respectively. When stratified by race and ethnicity, applications from Black women increased from 2.2% (87 of 4003) to 3.5% (215 of 6181) (P < .001) while applications from Black men remained unchanged (3.7% [150 of 4003] to 4.6% [284 of 6181]). While the matriculation rate for Black women remained unchanged (2.4% [46 of 1919] to 2.3% [52 of 2264]), the matriculation rate for Black men significantly decreased (3.0% [57 of 1919] to 2.4% [54 of 2264]; P = .04). Among Black graduates, there was a significant decline in graduation for men (4.3% [85 of 1967] to 2.7% [57 of 2147]; P = .03) with the rate among women remaining unchanged (1.7% [33 of 1967] to 2.2% [47 of 2147]). CONCLUSIONS AND RELEVANCE: Findings of this study show that the underrepresentation of Black physicians at every stage in surgical training pipeline persists. Black men are especially affected. Identifying factors that address intersectionality and contribute to the successful recruitment and retention of Black trainees in general surgery residency is critical for achieving racial and ethnic as well as gender equity.

Clinical applications of pelvic floor imaging: opinion statement endorsed by the society of abdominal radiology (SAR), American Urological Association (AUA), and American Urogynecologic Society (AUGS).

Pelvic floor dysfunction is prevalent, with multifactorial causes and variable clinical presentations. Accurate diagnosis and assessment of the involved structures commonly requires a multidisciplinary approach. Imaging is often complementary to clinical assessment, and the most commonly used modalities for pelvic floor imaging include fluoroscopic defecography, magnetic resonance defecography, and pelvic floor ultrasound. This collaboration opinion paper was developed by representatives from multiple specialties involved in care of patients with pelvic floor dysfunction (radiologists, urogynecologists, urologists, and colorectal surgeons). Here, we discuss the utility of imaging techniques in various clinical scenarios, highlighting the perspectives of referring physicians. The final draft was endorsed by the Society of Abdominal Radiology (SAR), American Urogynecologic Society (AUGS), and the American Urological Association (AUA).

Effect of Aspirin on Cancer Incidence and Mortality in Older Adults.

BACKGROUND: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. METHODS: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. RESULTS: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). CONCLUSIONS: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.

Study of Polyaniline/Poly(Sodium 4-Styrenesulfonate) Composite Deposits Using an Electrochemical Quartz Crystal Microbalance for the Modification of a Commercial Anion Exchange Membrane.

One of the intended applications for the modification of ion exchange membranes with polyaniline (PAni) is to use it as a matrix to include chemical species that confer a special property such as resistance to fouling or ion selectivity. In particular, the inclusion of polyelectrolyte molecules into the PAni matrix appears to be the way to modulate these properties of selective membranes. Therefore, it must be clearly understood how the polyelectrolyte is incorporated into the matrix of polyaniline. Among the results obtained in this paper using poly(sodium 4-styrenesulfonate) (PSS) and an electrochemical quartz crystal microbalance, the amount of polyelectrolyte incorporated into PAni is found to be proportional to the PSS concentration in solution if its value is between 0 and 20 mM, while it reaches a maximum value when the PSS in solution is greater than 20 mM. When the anion exchange membranes are modified with these composite deposits, the transport number of chloride was found to decrease progressively (when the PSS concentration in solution is between 0 and 20 mM) to reach a practically constant value when a concentration of PSS greater than 20 mM was used.

A Call to Action: Black/African American Women Surgeon Scientists, Where are They?

OBJECTIVE: To determine the representation of Black/AA women surgeons in academic medicine among U.S. medical school faculty and to assess the number of NIH grants awarded to Black/AA women surgeon-scientists over the past 2 decades. SUMMARY OF BACKGROUND DATA: Despite increasing ethnic/racial and sex diversity in U.S. medical schools and residencies, Black/AA women have historically been underrepresented in academic surgery. METHODS: A retrospective review of the Association of American Medical Colleges 2017 Faculty Roster was performed and the number of grants awarded to surgeons from the NIH (1998-2017) was obtained. Data from the Association of American Medical Colleges included the total number of medical school surgery faculty, academic rank, tenure status, and department Chair roles. Descriptive statistics were performed. RESULTS: Of the 15,671 U.S. medical school surgical faculty, 123 (0.79%) were Black/AA women surgeons with only 11 (0.54%) being tenured faculty. When stratified by academic rank, 15 (12%) Black/AA women surgeons were instructors, 73 (59%) were assistant professors, 19 (15%) were associate professors, and 10 (8%) were full professors of surgery. Of the 372 U.S. department Chairs of surgery, none were Black/AA women. Of the 9139 NIH grants awarded to academic surgeons from 1998 and 2017, 31 (0.34%) grants were awarded to fewer than 12 Black/AA women surgeons. CONCLUSION: A significant disparity in the number of Black/AA women in academic surgery exists with few attaining promotion to the rank of professor with tenure and none ascending to the role of department Chair of surgery. Identifying and removing structural barriers to promotion, NIH grant funding, and academic advancement of Black/AA women as leaders and surgeon-scientists is needed.

A Phase I Trial of Berberine in Chinese with Ulcerative Colitis.

The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.

A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal growth factor receptor signaling in aberrant crypt foci of the colorectum.

Colorectal cancer progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal growth factor receptor (EGFR) inhibitors are efficacious in advanced tumors including colorectal cancer. There is significant evidence that EGFR also plays important roles in colorectal cancer initiation, and that EGFR inhibitors block tumorigenesis. We performed a double-blind randomized clinical trial to test whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to colorectal cancer, and normal rectal tissue. A total of 45 patients were randomized to one of three erlotinib doses (25, 50, and 100 mg) with randomization stratified by nonsteroidal anti-inflammatory drug (NSAID) use. There were no unanticipated adverse events with erlotinib therapy. Erlotinib was detected in both normal rectal mucosa and ACFs. Colorectal ACF phosphorylated ERK (pERK), phosphorylated EGFR (pEGFR), and total EGFR signaling changes from baseline were modest and there was no dose response. Overall, this trial did not meet is primary efficacy endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely insufficient to merit further studies without additional prescreening stratification or potentially longer duration of use.

[Consensus conference of the Mexican Association for the Study of Climateric on veralipride prescription for patients with vasomotor symptoms]. / Consenso de la Asociación Mexicana para el Estudio del Climaterio para la indicación de veraliprida a pacientes con síntomas vasomotores.

Vasomotor symptoms are one of the main reasons for climateric women to consult a physician. Hormone therapy is the first treatment choice, but it is not indicated to all patients. Veralipride is an option for those who cannot or will not try hormone treatment. The Mexican Association for the Study of Climateric (AMEC) assembled an interdisciplinary group of medical experts so that they revised the medical literature on the subject and reached a consensus on veralipride indication, doses, counterindications and safety. The recommendations of the consensus conference on veralipride are: (1) Physicians must be familiar with its indication, side effects, pharmacokinetics and dosage. (2) Patients must be informed on other therapeutical options. (3) Patients' mental and neurological state must be evaluated, in particular to identify movement disorders, extrapyramidal symptoms (tremor or dystonia), anxiety and depression that can be mistaken for climateric symptoms. (4) Any adverse effect associated with the drug must be reported. (5) A random multicenter trial must be carried out in order to identify the frequency and severity of side effects, and (6) Written information on possible health risks when using the drug must be provided.

Comparison of a 6.5, 10, and 15 mm cryoablation catheter-tip for the treatment of common atrial flutter.

AIM: Only a few studies have investigated the effect of large tip sizes for catheter-based cryoablation (cryo). This study evaluates the safety and efficacy of cryo of the cavotricuspid isthmus (CTI) using three cryocatheter-tip sizes. METHODS AND RESULTS: Forty-five consecutive patients with common atrial flutter (AFL) underwent cryo of the CTI using a 6.5, a 10, or a novel 15 mm catheter-tip. Single applications of 3 min were delivered at each site along the CTI. Baseline characteristics of the three groups were comparable. The overall acute success rate was 89% and there was no difference with respect to the tip electrode size (P > 0.05). Fewer applications were required for a 10 mm (6 ± 2, range 3-7) and a 15 mm (6 ± 1, range 4-8) compared with a 6.5 mm catheter-tip (8 ± 3, range 4-14; P < 0.05). Procedure time was significantly shorter with the largest tip electrode (89 ± 26 min vs. 132 ± 28 min (6.5 mm tip), P < 0.05). No complications occurred. After a mean follow-up of 51 ± 5 months, 43 patients (96%) were without recurrence of AFL. CONCLUSIONS: A large (10 or 15 mm) cryoablation catheter-tip requires significantly fewer applications to create bidirectional CTI block compared with a 6.5 mm tip. A significant decrease in procedure time with preservation of the overall safety and efficacy supports the preference of a 15 over a 6.5 mm catheter-tip for cryoablation of AFL.

A suddenly lethal accessory pathway.

A 17-year-old girl was diagnosed with an asymptomatic Wolff-Parkinson-White pattern just before a major orthopedic operation. Three months after the surgery, she developed ventricular fibrillation-being the first manifestation of her Wolff-Parkinson-White syndrome. The patient was successfully reanimated. radiofrequency ablation permanently interrupted conduction over a right posteroseptal accessory pathway.

Catheter-based cryoablation of postinfarction and idiopathic ventricular tachycardia: initial experience in a selected population.

INTRODUCTION: Transvenous cryoablation has proven to be safe and effective for the treatment of supraventricular arrhythmias. The aim of this prospective study was to report the feasibility and safety of catheter-based cryoablation for the treatment of postinfarction and idiopathic ventricular tachycardia (VT). METHODS AND RESULTS: Catheter-based cryoablation was performed in 17 patients (15 men, 58 +/- 18 years). VT occurred after a prior myocardial infarction in 10 and was idiopathic in 7 patients. Cryoablation was performed with a 10-F, 6.5-mm tipped catheter. The ablation site was selected using entrainment mapping techniques for postinfarction VT. The site of the earliest activation time with optimal pace mapping was used for ablation of idiopathic VT. All targeted VTs (12 postinfarction and 7 idiopathic) were acute successfully ablated after a median number of 2 applications of 5 minutes with an average temperature of -82 +/- 4 degrees C. Mean procedure and fluoroscopy times were 204 +/- 52 and 52 +/- 20 minutes for postinfarction VT and 203 +/- 24 and 38 +/- 15 minutes for idiopathic VT. No cryocatheter or cryoenergy complications were observed. After a follow-up of 6 months, 4 of the 10 patients with postinfarction VT had a recurrence. In 1 of the 7 patients with idiopathic VT the index arrhythmia recurred. CONCLUSION: In this small patient population, catheter-based cryoablation of VT was safe and effective. Future studies are needed to evaluate the effect of cryothermy in a larger group of patients, especially those with postinfarction VT.

New ECG criteria in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

BACKGROUND: Desmosomal changes, electric uncoupling, and surviving myocardial bundles in fibrofatty tissue characterize arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Resultant activation delay is pivotal for reentry and thereby ventricular tachycardia (VT). Current task force criteria (TFC) for diagnosis have limited sensitivity. The aim of this study was to assess the diagnostic value of additional criteria on activation delay and VT to improve identification of affected individuals. METHODS AND RESULTS: ECG criteria were studied, while off drugs, in 50 index patients with proven ARVD/C according to TFC (TFC > or = 4 points) and 33 patients with probable ARVD/C (TFC 3 points, or TFC3), being 21 index patients and 12 family members of proven ARVD/C patients. Newly proposed additional criteria are (1) prolonged terminal activation duration in V(1)-V(3), an indicator of activation delay, (2) VT with left bundle-branch block morphology and superior axis, and (3) multiple VT morphologies. All index patients were screened for mutations in ARVD/C-related genes encoding desmosomal proteins. Altogether, 23 of 33 (70%) TFC3 patients fulfilled ARVD/C diagnosis when newly proposed criteria were applied additionally to current TFC. VT with left bundle-branch block morphology and superior axis or multiple VT morphologies were recorded in 12 and 9 of 33 TFC3 patients, respectively, all being index patients. When applying prolonged terminal activation duration additionally to TFC on depolarization/conduction abnormalities, 14 (42%) TFC3 patients fulfilled ARVD/C diagnosis. Results were not significantly different between mutation carriers and noncarriers. CONCLUSIONS: Adding the newly proposed criteria to current TFC for ARVD/C will improve identification of affected individuals importantly, independent of outcome of DNA analyses.

The atrioventricular interval during pre-excited tachycardia: a simple way to distinguish between decrementally or rapidly conducting accessory pathways.

BACKGROUND: Recognition of the presence and role of decremental fibers during wide QRS tachycardia requires carefully executed intracardiac studies. OBJECTIVE: This study sought to determine the value of the atrioventricular (AV) conduction time during pre-excited tachycardia to differentiate a fast from a decrementally conducting accessory pathway (AP). METHODS: Fifty-one patients with 56 pre-excited tachycardias were included in the study: Group I: 27 patients with 31 antidromic tachycardia (ADT) using an atriofascicular pathway, Group II: 2 patients with pre-excited tachycardia due to bystander AV conduction, Group III: 3 patients with ADT and a short AV Mahaim fiber, and Group IV: 19 patients with 21 ADT using a fast conducting right-sided AP. The AV interval was measured in the His bundle electrogram and related to the tachycardia cycle length (TCL) by making an AV/TCL index. RESULTS: An AV interval > or = 150 ms during pre-excited tachycardia yielded a 91% sensitivity, 90% specificity, positive predictive value of 94%, and negative predictive value of 83% for AV conduction over a decrementally conducting pathway, whereas a > or =0.55 AV/TCL index yielded a sensitivity of 89%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 84%. In 3 of 4 patients with Mahaim fibers and a <0.55 AV/TCL index, a prolonged ventriculoatrial (VA) conduction time was found. CONCLUSIONS: An AV interval > or =150 ms during pre-excited tachycardia is a fast and reliable method for detecting a decrementally conducting AP. Correcting the AV interval by the tachycardia cycle length improved specificity and positive predictive accuracy.