A Molecular Imaging "Skin A Time-resolving Intraoperative Imager for Microscopic Residual Cancer Detection Using Enhanced Upconverting Nanoparticles.

Optimal cancer therapy requires targeted and individualized treatment of all tumor cells, including both gross and microscopic disease. Intraoperatively hard to visualize and often left behind, microscopic foci of residual cancer cells significantly increase the risk of cancer recurrence and treatment failure rates. Fluorescently-tagged targeted molecular labels are employed to guide surgery, but conventional fluorescent intraoperative imagers suffer from lack of sensitivity and maneuverability, limiting practicality in small tumor cavities owing to their cumbersome sizes driven by optics. This work does away with conventional lenses and filters and introduces an optics-free molecular imaging "skin" consisting of only a $25\mu \mathrm{m}$ thin CMOS contact imager that synergistically integrates the long emission lifetimes of upconverting nanoparticles (UCNP) combined with upconversion to use a time domain approach to acquire the image coupled with infrared illumination allowing deep tissue penetration and elimination of autofluorescence. Using this strategy, we are able to visualize UCNPs at fluences (W/cm2) compatible with intraoperative use, opening the door to visualize targeted areas with microscopic sensitivity and facilitate residual microscopic disease detection during surgery, and laying the groundwork for precision post-operative radiation.

Establishing a standardized quality management system for the European Health Network GA2LEN.

BACKGROUND: Quality management is increasingly important in clinical practice. The Global Allergy and Asthma European Network (GA(2)LEN) is a network of clinical and scientific excellence with originally 25 allergy centres in 16 European countries, a scientific society (European Academy of Allergology and Clinical Immunology), and a patient organization (European Federation of Allergy and Airways Diseases Patients' Associations). Although some allergy centres adhere to internal quality criteria, the implementation of a standardized quality management system for allergy centres across Europe was lacking. OBJECTIVES: To implement standardized quality criteria among allergy centres organized within GA(2)LEN and thus ensure equal standards of diagnosis and care as well as to establish a culture of continuous quality improvement. METHODS: Quality criteria covering, e.g., diagnostic and therapeutic procedures, and emergency preparedness to assure patient safety were developed and agreed upon by all 25 participating centres. To assure implementation of quality criteria, centres were audited to check quality indicators and document deviations. A follow-up survey was used to assess the usefulness of the project. RESULTS: Deviations were documented mainly in the areas of emergency care/patient safety (27.3% lacked regular emergency training of doctors and nurses; 22.7% inadequate emergency intervention equipment; 22.7% lacked critical incidence reporting/root cause analyses) and handling of extracts/pharmaceuticals (31.8% lacked temperature logs of fridges; 4.5% inadequate check of expiration dates). Quality improvement was initiated as shown by findings of re-audits. Usefulness of the project was rated high. CONCLUSION: The establishment of a quality management system with joint standards of care and harmonized procedures can be achieved in an international health network and ensures quality of care.

Delivery of asthma and allergy care in Europe.

BACKGROUND: There is no comprehensive information available concerning the way in which care is provided for those with allergic conditions in Europe. OBJECTIVE: To determine who cares for those with asthma, allergic dermatitis, and rhinitis in Europe and to determine the involvement of primary care and other healthcare professionals and the use of patient education and guidelines. METHODS: A questionnaire survey of colleagues in 43 institutions in 33 European countries with results being related to published sources of information regarding prevalence of allergic diseases in different countries and published data regarding availability of doctors and expenditure on healthcare. RESULTS: A total of 33 of 43 institutions completed the survey (76.7%) with information being obtained from 26 of the 33 countries surveyed (78.7%). There are wide differences in the use of different healthcare professionals in different countries, with those for asthma, for example, being most likely to be cared for by an allergologist in some countries and by a primary care physician in many others. There was much greater awareness of guidelines for asthma and little reported usage of guidelines in the management of those with allergic skin diseases, and while self-management education was offered most to those with asthma, there was a wide variation in the usage of group education. CONCLUSIONS: Many of the differences revealed by this survey cannot be explained by the availability of different healthcare professionals nor by differences in healthcare expenditure, and such differences need further evaluation to determine their effect on outcomes and the economics of healthcare so that we may determine that which is optimal.

Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release.

BACKGROUND: Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved. OBJECTIVE: To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro. METHODS: BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured. RESULTS: RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8. CONCLUSION: HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.

Treatment of rosacea with intense pulsed light: significant improvement and long-lasting results.

BACKGROUND: Rosacea is a common skin condition but the treatments currently available are not satisfactory. OBJECTIVES: To assess the efficacy of intense pulsed light (IPL) for treatment of stage I rosacea (flushing, erythema and telangiectasia). METHODS: Thirty-four patients were treated, 25 women and nine men, mean age 47 years. The treatment employed was IPL 515-1200 nm, with a 560 nm cut-off filter. The fluence range was 24-32 J cm(-2). Four treatments were administered on the face at 3-week intervals. Erythema values were measured at baseline and at the end of the treatment period on the cheeks and chin. Digital photographs were assessed by a consultant dermatologist on a 10-point visual analogue scale (VAS). Patients' assessments were also made using a 10-point VAS. Outcome measures were repeated 6 months after treatment. RESULTS: After four treatments the mean reduction of the erythema values was 39% on the cheeks (P < 0.001) and 22% on the chin (P < 0.001). This was confirmed by photographic assessment where erythema improved by 46% and telangiectasia by 55% (P < 0.001). The severity of rosacea was reduced on average by 3.5 points on the 10-point VAS. Patients' and physicians' assessments of the overall improvement of rosacea were similar: more than 50% improvement was noticed in 73% and 83% of patients, respectively (P < 0.001). The results were sustained at 6 months. Side-effects were minimal and self-limiting. CONCLUSIONS: IPL significantly reduces erythema and telangiectasia of rosacea and this is sustained for at least 6 months.

Modulation of the epithelial inflammatory response to rhinovirus in an atopic environment.

BACKGROUND: Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations. OBJECTIVE: To evaluate the effect of the environment resulting from an atopic immune response on RV-induced epithelial inflammation, replication and cytotoxicity. METHODS: Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS-2B) cells were infected with RV in the presence of conditioned media from RV-stimulated PBMC cultures. IL-6, IL-8, RANTES and TGF-beta1 levels were measured by ELISA, RV-induced cytotoxicity by a colorimetric method and RV titres on Ohio-HeLa cells. RESULTS: RV-induced epithelial production of IL-6, IL-8 and RANTES was significantly lower, while TGF-beta1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the 'atopic' environment also resulted in elevated RV titres and increased RV-induced cytotoxicity. CONCLUSIONS: Under the influence of an atopic environment, the epithelial inflammatory response to RV is down-regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up-regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling.

Hospitalizations for childhood asthma in Athens, Greece, from 1978 to 2000.

Trends in rates of asthma admissions among children have shown a variety of patterns in different countries in the last decades. We undertook the present study to determine the time trends in asthma admissions and readmissions of children in Athens, Greece. Data were obtained retrospectively from hospital registries of the three main children's hospitals in Athens from 1978 to 2000. Children admitted with the diagnoses of asthma, asthmatic bronchitis or wheezy bronchitis were included. Hospital admission rate for asthma among children 0-14 yr from 1978 to 2000 rose by 271% (p <0.001). The rise in rates among those aged 0-4 and 5-15 yr were 250% and 276%, respectively. The mean annual increase in admission rate was 12.2% for 1978-1987, 4.7% for 1988-1993 and 0.6% for 1994-2000. The readmission rate among children 0-14 yr was increased from 15.3% to 23.3%. A positive correlation between admission and readmission rates in all age groups was observed. In conclusion, our findings show an increase in the childhood asthma admission rate in Athens in late 1970's and during the 1980's, which has decelerated in the 1990's, particularly in the second-half of the decade. The readmission rate paralleled that of admissions over the entire study period.

Expression of costimulatory molecules in peripheral blood mononuclear cells of atopic asthmatic children during virus-induced asthma exacerbations.

BACKGROUND: Respiratory viruses are the most frequent triggers of acute asthma exacerbations. Herein we investigate costimulatory molecule expression on peripheral blood mononuclear cells (PBMC) during such exacerbations. METHODS: Eleven children with atopic asthma were followed prospectively and respiratory symptoms were recorded on diary cards. A blood sample and nasopharyngeal wash (NPW) were obtained at baseline and subsequently during an exacerbation. PBMC were immunophenotyped using flow cytometry. NPW samples were examined for the presence of respiratory viruses by RT-PCR. RESULTS: A virus was detected in 73% of exacerbations and none at baseline. A drop of NK cells and a marginal increase of monocytes were the only changes of cell count during the exacerbation. A significant downregulation of B7-2 on NK cells and of B7-1 on monocytes was also observed during exacerbations. CONCLUSIONS: The above observations are in contrast to in vitro findings showing an upregulation of costimulatory molecules after exposure of blood cells to viruses or allergens. It is possible that activated immune cells leave the blood stream to migrate to the inflammation site during acute asthma exacerbations.

The use of three-dimensional ultrasound for fetal gender determination in the first trimester.

The objective of this study was to examine the accuracy of fetal gender prediction at a routine first trimester scan using three-dimensional (3D) ultrasound. 200 women were recruited for this study and they agreed to have a transvaginal scan for their routine first trimester scan for fetal anatomy and nuchal thickness measurement. 3D volumes were obtained and stored. Two examiners independently reviewed all the volumes and recorded their diagnosis of fetal gender and measured the angle between the genital tubercle and the skin overlying the sacrum. After studying the 3D volumes both examiners recorded a diagnosis of male or female in 150 cases (81.5%). In 34 cases (18.5%) either both (n=21) or one of them (n=13) could not comment on fetal gender by studying the saved volume. From these 150 cases correct prediction of fetal gender by both examiners was achieved in 85.3% of cases. In 6.7% of cases both examiners predicted the wrong gender while for the rest 8% of cases each examiner assigned different gender to the fetus (k=0.84; standard error 0.045). Angle measurements performed from the saved 3D volumes were highly reproducible. Gestational age did not affect the accuracy of gender identification. This study demonstrates that 3D ultrasound can be an effective and fast way of identifying fetal gender in the first trimester. The advantages of 3D ultrasound stem from its ability to virtually reproduce all required views.

Clinical aspects of food allergy.

Food allergy affects 2.5% of adults and 6-8% of children, and is a leading cause of life-threatening anaphylactic episodes. Food allergy is defined as an adverse reaction to foods that is mediated immunologically and involves specific IgE or non-IgE mechanisms. In this review only IgE-related food allergy will be considered. Many food allergens are glycoproteins, but they do not share any striking biochemical similarities. The definition of many food proteins at the molecular level has tremendously facilitated our understanding of clinical syndromes and seemingly bizarre observations. Clinical manifestations of food allergy include symptoms of the gastrointestinal, cutaneous and respiratory systems, as well as systemic anaphylaxis. The diagnosis of food allergy involves a stepwise approach, including medical history taking, demonstration of specific IgE and confirmation by oral food challenge. The management of the food-allergic patient at present consists of avoidance of the culprit food and education, while future advances may include specific immunotherapy with modified allergens or DNA vaccination.

The influence of maternal hematocrit on placental development from the first to the second trimesters of pregnancy.

OBJECTIVES: To study the influence of maternal hematocrit (Ht) and hemoglobin (Hb) levels on placental size and growth in the first and mid-second trimesters of pregnancy. SUBJECTS/METHODS: This was a prospective study performed at the fetal medicine unit of a university hospital. One hundred and eighty-one women with a singleton pregnancy were recruited at 11-14 weeks' gestation. For each case three scans of the placenta were performed, the first at recruitment and the following two at 3-week intervals. The volume of the placenta was measured at each visit using a three-dimensional ultrasound scanner. The maternal Hb and Ht were measured within 2 weeks of the first scan. RESULTS: The placental growth during the second trimester was inversely related to the Ht levels (r = -0.29, P = 0.001). It was also related to the Hb level (r = -0.20, P = 0.021). An increase of 0.1 units of Ht was associated with 38% less growth of the placenta (95% confidence interval: 18-54% less growth). DISCUSSION: This study demonstrates the effects of maternal environment on placental growth. Our data suggest that the levels of Ht appear to affect the placental growth during the second trimester. Further studies on the factors that regulate placental growth are needed to elucidate the pathophysiology of these interactions and their effect on pregnancy outcome.

Assessment of fetal anatomy in the first trimester using two- and three-dimensional ultrasound.

The objective of this study was to perform a complete anatomical survey of the fetus at 12-13 weeks gestation using stored volumes acquired by a three-dimensional (3D) scanner. 159 consecutive women at 12-13 weeks gestation who had a routine early pregnancy scan in our unit were recruited. A complete survey of the fetal anatomy was attempted by two-dimensional (2D) transabdominal and, if needed, transvaginal ultrasound. Then, using a 3D transvaginal probe, two volumes of the whole fetus were acquired. A complete anatomical survey (excluding anatomy of the heart) was attempted using the stored data. A complete anatomical survey was achieved in 93.7% (149) of cases with 2D ultrasound compared to 80.5% (128) of cases with 3D volume acquisition (p<0.001). The nuchal translucency was measured with 2D scanning in 98.7% of cases and in 91.8% of cases using 3D volumes. The mean time to perform a 2D scan was 12.2 min standard deviation (SD 3.4 min) while the mean time to obtain and examine the stored volumes was 8.4 min (SD 1.45 min, p<0.001). Real-time 2D ultrasound is still the best way to examine fetal anatomy in the first trimester. However, 3D ultrasound can be a useful addition to clinical practice, providing views not easily obtained by conventional 2D ultrasound. It can potentially minimize actual scanning time and provides an excellent way to store scanned data.

Different patterns of interatrial conduction in clockwise and counterclockwise atrial flutter.

BACKGROUND: The terms counterclockwise (CC) and clockwise (C) atrial flutter (Afl) are used to describe right atrial activation around the tricuspid valve in the left anterior oblique view. The manner in which the left atrium is activated, as reflected by coronary sinus (CS) recordings, has not been systematically evaluated. METHODS AND RESULTS: Nine patients with both CC and C Afl underwent electrophysiological study with CS recordings during both rhythms with the use of a decapolar catheter with the tip placed in the distal CS. Patterns of CS activation during each type of Afl as well as during during sinus rhythm were categorized into 1 of 3 patterns: sequential proximal-to-distal, sequential distal-to-proximal, and fused, indicating activation from different directions. In 7 of 9 patients, the pattern of CS activation in CC Afl and C Afl differed, with a proximal-to-distal pattern in CC Afl and a fused pattern in C Afl. In 2 patients, pacing the high right atrial septum near the presumed site of Bachmann's bundle in sinus rhythm showed a similar fused pattern of CS activation. CONCLUSIONS: These results demonstrate different patterns of CS activation in CC Afl and C Afl in the majority of patients and are consistent with a model in which the left atrium is activated predominantly over Bachmann's bundle during C Afl and over the CS os in CC Afl. These findings may have implications for maintenance of Afl, interpretation of flutter wave morphology on surface ECG, and left atrial mechanical function in Afl.

AE anion exchangers in atrial tumor cells.

Intracellular pH homeostasis and intracellular Cl(-) concentration in cardiac myocytes are regulated by anion exchange mechanisms. In physiological extracellular Cl(-) concentrations, Cl(-)/HCO(3)(-) exchange promotes intracellular acidification and Cl(-) loading sensitive to inhibition by stilbene disulfonates. We investigated the expression of AE anion exchangers in the AT-1 mouse atrial tumor cell line. Cultured AT-1 cells exhibited a substantial basal Na(+)-independent Cl(-)/HCO(3)(-) (but not Cl(-)/OH(-)) exchange activity that was inhibited by DIDS but not by dibenzamidostilbene disulfonic acid (DBDS). AT-1 cell Cl(-)/HCO(3)(-) activity was stimulated two- to threefold by extracellular ATP and ANG II. AE mRNAs detected by RT-PCR in AT-1 cells included brain AE3 (bAE3), cardiac AE3 (cAE3), AE2a, AE2b, AE2c1, AE2c2, and erythroid AE1 (eAE1), but not kidney AE1 (kAE1). Cultured AT-1 cells expressed AE2, cAE3, and bAE3 polypeptides, which were detected by immunoblot and immunocytochemistry. An AE1-like epitope was detected by immunocytochemistry but not by immunoblot. Both bAE3 and cAE3 were present in intact AT-1 tumors. Cultured AT-1 cells provide a useful system for the study of mediators and regulators of Cl(-)/HCO(3)(-) exchange activity in an atrial cell type.

Incidence and predictors of myocardial infarction among patients with atrial fibrillation.

OBJECTIVES: We sought to evaluate the utility of excluding myocardial infarction (MI) in patients presenting to the emergency department (ED) with atrial fibrillation (AF) and to identify predictors of MI in this group. BACKGROUND: Patients with AF are frequently admitted to the hospital, in part, to exclude an associated MI. There are no prospective data on unselected patients to support this common practice. METHODS: We conducted a prospective cohort study of all patients who presented to a single-center ED with the primary diagnosis of AF. RESULTS: Of a total of 255 patients, 190 (75%) were admitted to the hospital, and 109 of them underwent a standard "rule-out MI" protocol. Of these 109 patients, six (5.5%) were identified as having an acute MI at the time of admission. Chest pain was present in 39% of patients, with a sensitivity and specificity for the occurrence of MI of 100% and 65%, respectively. ST segment elevation or depression was present in 43% of patients, with a sensitivity and specificity of 100% and 51%. The presence of either major ST segment depression (>2 mm) or elevation on the admission electrocardiogram (ECG) was present in 6%, with a sensitivity of 100% and a specificity of 99%. The resulting positive and negative predictive values were 86% (95% confidence interval [CI] 42% to 99%) and 100% (95% CI 96% to 100%), respectively. Use of this criterion would have reduced the number of rule-out MIs in our study group by 94%, with no loss of sensitivity. CONCLUSIONS: Chest pain and ST segment depression are extremely common findings in patients presenting to the ED with AF and have limited power to predict MI. In contrast, ECG evidence of ST segment elevation or depression >2 mm appears to be a reliable discriminator of which patients are at risk for MI. Patients without significant ST segment changes are at very low risk for MI and may not require performance of the rule-out MI protocol or hospital admission if clinically stable.

Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris.

In this study we have evaluated the use of blue light (peak at 415 nm) and a mixed blue and red light (peaks at 415 and 660 nm) in the treatment of acne vulgaris. One hundred and seven patients with mild to moderate acne vulgaris were randomized into four treatment groups: blue light, mixed blue and red light, cool white light and 5% benzoyl peroxide cream. Subjects in the phototherapy groups used portable light sources and irradiation was carried out daily for 15 min. Comparative assessment between the three light sources was made in an observer-blinded fashion, but this could not be achieved for the use of benzoyl peroxide. Assessments were performed every 4 weeks. After 12 weeks of active treatment a mean improvement of 76% (95% confidence interval 66-87) in inflammatory lesions was achieved by the combined blue-red light phototherapy; this was significantly superior to that achieved by blue light (at weeks 4 and 8 but not week 12), benzoyl peroxide (at weeks 8 and 12) or white light (at each assessment). The final mean improvement in comedones by using blue-red light was 58% (95% confidence interval 45-71), again better than that achieved by the other active treatments used, although the differences did not reach significant levels. We have found that phototherapy with mixed blue-red light, probably by combining antibacterial and anti-inflammatory action, is an effective means of treating acne vulgaris of mild to moderate severity, with no significant short-term adverse effects.

Chloroxylenol and zinc oxide containing cream (Nels cream) vs. 5% benzoyl peroxide cream in the treatment of acne vulgaris. A double-blind, randomized, controlled trial.

Forty-one subjects completed a double-blind controlled randomized study comparing the following: (i) Nels cream (containing chloroxylenol and zinc oxide); (ii) 5% benzoyl peroxide cream; and (iii) the vehicle of the Nels cream. Patients applied the medications twice daily for 8 weeks. At the end of the test period there was no significant difference in the reduction of inflammatory and noninflammatory lesion counts achieved by Nels cream and benzoyl peroxide. Both creams proved superior to the vehicle. Efficacy grading by subjects and investigators showed no significant difference between Nels cream and benzoyl peroxide. However, side-effects such as peeling and dryness caused by the treatment were significantly less in the Nels cream group.

Absence of transplacental passage of the low molecular weight heparin enoxaparin.

BACKGROUND: Venous thromboembolism (VTE) during pregnancy and puerperium remains a major cause of maternal morbidity and mortality. The use of low molecular weight heparin (LMWH) constitutes a promising alternative for the prevention of VTE instead of unfractionated heparin as it can be administered subcutaneously once daily and without coagulation measurement. Unfortunately, the safety of LMWHs administration for the mother and fetus has not been well established. STUDY DESIGN: In order to examine the safety of enoxaparin to the fetus, 24 women were recruited and 40 mg of enoxaparin was administered in 14 of them. All 24 women were going to have an early termination of pregnancy due to major fetal malformations. Maternal blood samples were drawn before and after the injection of enoxaparin, while fetal blood samples were taken only after the drug administration. Anti-IIa and anti-Xa activities were measured. RESULTS: A statistically significant increase of anti-Xa activity in the mothers studied was pointed out, while there was no detection of anti-IIa and anti-Xa activities in the fetuses. CONCLUSIONS: Since no anti-IIa and anti-Xa activities were detected in the fetuses' blood samples, it is concluded that enoxaparin does not cross the placenta and therefore appears safe for the fetus.

Presence and significance of the left atrionodal connection during atrioventricular nodal reentrant tachycardia.

It has been suggested that the anatomic substrates of dual atrioventricular nodal pathways are likely to be the atrionodal connections. During atrioventricular nodal re-entrant tachycardia (AVNRT) or ventricular pacing (VP), an earliest retrograde atrial activation in the coronary sinus (CS) distal to the ostium (CS breakthrough) would suggest the presence of an exit from a left atrionodal connection. The aim of the study was to evaluate the incidence of such an atrial retrograde activation in the CS during AVNRT and VP. The retrograde atrial activation was recorded during typical AVNRT (38 patients, 27 women, mean age 44 +/- 18 years) by a multipolar catheter in the CS, a decapolar catheter in the His bundle position, and a deflectable quadripolar catheter along the tricuspid annulus anterior to the CS ostium. In 31 patients the retrograde atrial activation was recorded also during VP at a similar cycle length. A CS breakthrough was found in 18 patients during AVNRT (47%) and in 13 patients during VP (42%). Presence or absence of CS breakthrough was concordant between AVNRT and VP in 90% of the patients. A CS breakthrough, suggesting a left-sided atrionodal connection, is frequently recorded both during AVNRT and VP. In patients with a CS breakthrough pattern, the absence of correlation between the His bundle to the earliest CS retrograde atrial electrogram interval and AVNRT cycle length, or any other atrial activation times recorded in the posterior and anterior region of the Koch's triangle, would suggest that the left-sided atrionodal connection is a bystander during typical AVNRT.