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Multiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion.This study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators.The study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course.VX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Volta Medical Saint Joseph Hospital Marseille, France Background Spatiotemporal dispersion is an electrical footprint of atrial fibrillation (AF) drivers that has been successfully implemented to target extra-pulmonary veins (PVs) regions during persistent AF ablation. Purpose The aim of the study is to characterize spatiotemporal dispersion extent and location and to compare dispersion atrial localization and extent between pacing-induced AF and spontaneous AF. Methods Spatiotemporal dispersion maps were built with an artificial intelligence software (VX1, Volta Medical) and analyzed in 71 consecutives persistent (66%) and long-standing persistent (34%) AF patients admitted for a first ablation procedure. Fifty-two patients were in spontaneous AF (73%) at the outset of the procedure while AF was induced in 19 patients (27%) by burst pacing ± isoproterenol infusion. A semi-quantitative visual quantification of dispersion extent was conducted by implementing an atrial segmentation into 22 regions and a region-centered score from 0 (no dispersion) to 3 (high dispersion). Also, an automated quantification was performed as follows: (i) a gradient filter designed to extract atrial shapes from background was applied, (ii) dispersion areas were segmented using a color thresholding method, and (iii) a structuring element was used to connect segmented dispersion areas. Results The regional characterization of dispersion shows that dispersion distribution follows a similar pattern and is present in similar atrial regions, regardless of whether AF is spontaneous or induced (Figure 1). Global dispersion extent, however, is significantly higher in the left atrium of patients in spontaneous AF compared to patients with induced AF (15.43% ± 9.04 versus 9.86% ± 6.41, P=0.0025, Figure 2). Accordingly, the regional dispersion score tends to be lower when AF is induced. Dispersion hotspots are: LSPV anterior antrum -ridge (R1), RSPV anterior antrum (R5), anterior wall (R9), roof (R10), posterior wall (R11), and low left atrial septum (R15) in the left atrium. In the right atrium: low right atrial septum (R15) and posterior right atrium (R20) (Figure 1). Conclusions Artificial intelligence-enabled dispersion persistent AF mapping indicates that dispersion is reduced in induced vs. spontaneous-AF but that its distribution follows a similar pattern.

Introduction In recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC). A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed. Materials and methods Annex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p, Journal of Preventive Medicine and Hygiene, Vol 60, No 1 (2019): 2019601

This article examines the presence and uses of plants attested in the Chinese medical tradition in the materia medica literature of classical antiquity. It is based on the consultation of the major ancient compilations on materia medica of Chinese medicine and classical antiquity, specifically Bencao Gangmu by Li Shizhen (16th cent.) and De materia medica by Dioscorides (1st cent. A.D.). The article is divided in three major parts: the identification of plants used in the Chinese medical tradition in the medicine of the Mediterranean World in Antiquity; the analysis of the knowledge of these plants and their origin in classical antiquity; a comparison of the uses of these plants in the Bencao Gangmu and De materia medica. It traces the presence of plants of the Chinese medical tradition in Classical antiquity. Although their exact origin was not known, they were reputed at that time to be native to either India or the Black Sea, two areas that correspond to the ending points of the Silk Road. As for their uses in both traditions, they correspond for some plants, whereas they do not for others because either the uses attested in the Chinese tradition were not preserved on the Mediterranean or different uses appeared in the Mediterranean tradition. These differentiated uses hint at both continuities and ruptures, with the latter resulting from the long journey of the plants from the Chinese World to the Mediterranean and, at the same time, attempts aimed to diversify and optimize the applications of non-native medicinal substances.

Mapping of Scar-Related VTBackground Substrate-based VT ablation is mostly based on maps acquired with ablation catheters. We hypothesized that multipolar mapping catheters are more effective for identification of scar and local abnormal ventricular activity (LAVA). Methods and results Phase1: In a sheep infarction model (2 months postinfarction), substrate mapping and LAVA tagging (CARTO®3) was performed, using a Navistar (NAV) versus a PentaRay (PR) catheter (Biosense Webster). Phase2: Consecutive VT ablation patients from a single center underwent NAV versus PR mapping. Point pairs were defined as a PR and a NAV point located within a 3D-distance of ≤3 mm. Agreement was defined as both points in a pair being manually tagged as normal or LAVA. Four sheep (4 years, 50 ± 4.8 kg) and 9 patients were included (53 ± 14 years, 8 male, 6 ischemic cardiomyopathy). Mapping density was higher within the scar with PR versus NAV (3.2 vs. 0.7 points/cm2, P = 0.001) with larger bipolar scar area (68 ± 55 cm2 vs. 58 ± 48 cm2, P = 0.001). In total, 818 point pairs were analyzed. Using PR, far-field voltages were smaller (PR vs. NAV; bipolar: 1.43 ± 1.84 mV vs. 1.64 ± 2.04 mV, P = 0.001; unipolar; 4.28 ± 3.02 mV vs. 4.59 ± 3.67 mV, P < 0.001). More LAVA were also detected with PR (PR vs. NAV; 126 ± 113 vs. 36 ± 29, P = 0.001). When agreement on LAVA was reached (overall: 72%; both LAVA, 40%; both normal, 82%) higher LAVA voltages were recorded on PR (0.48 ± 0.33 mV vs. 0.31 ± 0.21 mV, P = 0.0001). Conclusion Multipolar mapping catheters with small electrodes provide more accurate and higher density maps, with a higher sensitivity to near-field signals. Agreement between PR and NAV is low.

Unipolar Signal and Atrial Flutter AblationIntroduction Complete elimination of the negative component of the unipolar atrial electrogram recently proved predictive of lesions transmurality. We prospectively assessed its relevance as a real-time local ablative endpoint for each individual lesion created across the cavotricuspid isthmus (CTI) in order to constitute a line of bidirectionnal block during common atrial flutter (AFL) ablation. Methods and Results Sixty-two consecutive patients underwent common AFL ablation following an electrophysiological approach guided by real-time electrogram modification analysis. In 31 patients (unipolar group), the local ablative endpoint was complete elimination of the negative component of the unipolar atrial electrogram, while the other 31 patients (control group) were treated following our standard approach based on the currently used local ablative endpoint defined by a ≥50% amplitude decrease of the bipolar atrial electrogram. Bidirectional block was achieved in all patients (mean age 67.9 ± 11.5 with 80.6% of men). Mean ablation time (164.3 ± 88.3 seconds vs 332.8 ± 151.5 seconds; P < 0.001) and mean energy delivery (7.5 ± 4.1 kJ vs 14.2 ± 6 kJ; P < 0.001) were significantly shorter in the unipolar group compared to the control group. No statistical differences were seen in procedure time (68.5 ± 22.6 min vs 77.5 ± 20.2 min; P = 0.10). Conclusion Real-time unipolar electrogram modification is a relevant local endpoint during common AFL ablation and leads to a substantial reduction of ablation time and energy delivery compared to a standard ablative approach while displaying a similar short- and long-term success rate.

Background— It has been experimentally shown that elimination of the negative component of the unipolar atrial electrogram (R morphology completion) during radiofrequency applications reflects transmural lesions creation. Subsequently, it has been clinically suggested that such a transmurality can be either irreversible or reversible. The present study is aimed to determine, at the histological level, whether transmural lesions, assessed by R morphology completion, might indeed be reversible in some circumstances or not. Methods and Results— In 6 Mongrel hound dogs, superior and inferior vena cavae were isolated and individual lesions were created in the right atrium using radiofrequency energy (30 W/48°C/17 mL/min as presettings and 10 g of force in average) under CARTO guidance. Five types of lesions were created; R + 0: termination of ablation at the time of R morphology completion; R + 5, R + 10, or R + 20: extension of ablation for 5, 10, or 20 seconds, respectively, after R morphology achievement; and conventional: radiofrequency applications lasting 30 seconds irrespective of the atrial electrogram modification. All conventional, R + 5, R + 10, and R + 20 lesions were necrotic and transmural, whereas some R + 0 lesions were not (comprising a part of necrosis and a part of reversible cell damage). Interestingly, surrounding organ injuries were observed after conventional, R + 10, and R + 20 radiofrequency applications but were not observed after R + 0 and R + 5 applications. Conclusions— Elimination of the negative component of the unipolar atrial electrogram reflects, in general, irreversible transmural necrosis creation. In some cases, however, it translates transmural lesion only (with potential reversibility) likely related to transient cell damage creation.

When the meningococcus B vaccine was introduced into Italy in 2017, it was recommended for newborns based on national epidemiological data indicating that they were at greater risk. However, the vaccination service of the local health authority of L'Aquila had already been receiving spontaneous parental requests to provide vaccination for children in lower-risk age groups from the beginning of 2016. We therefore decided to use a self-administered questionnaire in order to investigate the parents' socio-demographic data; their children's history of other recommended vaccinations (against measles, mumps and rubella, varicella, meningococcus C and, for females, human papilloma virus); the information sources concerning meningococcal vaccination; and the timing of its administration. The questionnaire was completed by 565 parents, and the results showed that the requests mainly came from the parents of children aged 5-11 years. The children whose mothers had received a high school education and were >35 years old were more likely to have received the first dose after the age of one year and to have perceived pain at the inoculation site, and less likely to have experienced mild general reactions. The requests were mainly trigged by the recommendations of healthcare professionals, and the overloading of the vaccination service led to delays in the administration of the doses after the first. The delays (reported by 74.07% of the parents) were mainly due to organisational problems in the service itself, which led 61.52% of the doses being more appropriately administered by staff working as private physicians inside public health facilities, albeit at extra cost. These findings indicate that organisational factors and excessive demand had a considerable impact on both the efficacy of the immunisation and its appropriateness.

Background— In patients treated for paroxysmal atrial fibrillation, the pulmonary vein (PV) reconnection rate is substantial and may be related to the lack of transmurality achievement while performing PV isolation (PVI). It has been experimentally demonstrated that positive unipolar atrial electrogram completion, when applying radiofrequency energy, was associated with transmural lesions. In this regard, we seek to determine whether the unipolar signal modification may be an appropriate end point for point-by-point radiofrequency application and find out whether it could improve the paroxysmal atrial fibrillation ablation results in humans. Methods and Results— Fifty consecutive patients (61±8 years old, 41 men) with paroxysmal atrial fibrillation underwent PVI using Carto and Lasso. Each radiofrequency application lasted until development of a completely positive unipolar electrogram. Fifty patients (63±9 years old, 40 men), who previously underwent PVI following the standard approach of our institution, corresponded to the control group. All PVs were isolated in all patients of both groups. However, the procedural and ablation times were significantly lower in the unipolar group compared with those of the control group, whereas the PV reconnection rate, after 30 minutes of waiting time, was not significantly different. Overall, 21±4 months after 1 PVI session, the sinus rhythm maintenance rate without antiarrhythmic drugs was significantly higher ( P =0.027) in the unipolar group (88%) compared with that of the control group (70%). Conclusions— Unipolar signal modification is a useful end point for radiofrequency energy delivery in patients with paroxysmal atrial fibrillation who undergo PVI and leads to a substantial midterm sinus rhythm maintenance rate.

Ethnopharmacological relevance : Transmission of ethnopharmacological knowledge over a long period of time and across a vast area or between botanically or culturally/scientifically unrelated regions of the world is a fundamental issue in ethnopharmacology, as it traces continuity and transformation(s) of the data to be submitted to analysis for evaluation. In the context of present interest in Eastern medicine (particularly Indian and Chinese), we ask questions about the transmission of knowledge from the East to the Mediterranean. In the first part, we survey available literature on trade between the two areas and, in the second, we present preliminary micro-cases (data, analysis and interpretation) in order to verify the feasibility of a comparative study. Materials and methods Based on the assumption of native areas of origin and/or domestication of plants and one other natural product (musk), we have screened relevant sources (pharmacological literature) in the original language searching for explicit information about Indian and/or Chinese materia medica. We have concentrated our attention on knowledge of the origin of the materia medica under study, their therapeutic applications, the explanations provided for their activity, and the knowledge of the living plants and animals as demonstrated through their representations. Results Relevant data come from the Hippocratic Collection in ancient Greece (5th century B.C.E.) to the Renaissance in the 16th century. The corpus of materia medica and drugs collected in this preliminary study include pepper and myrrh (5th century B.C.E.), ginger (1st century C.E.), a dozen plants and drugs in the period 9th to 13th century (e.g. camphor, clove, galanga, nutmeg), cinnamon (11th century and later), eggplant, banana tree and musk (13th–16th century). Whereas the Eastern origin of such products was known, the exact area was not always. Judging from their representations, the plants and animals producing the drugs studied here were not necessarily known. Compared therapeutic uses of the drugs did not correspond to those in the area of origin, even though some knowledge of such original uses was preserved. Conclusions This study warrants the very possibility of a comparative analysis of different historical pharmacological traditions. It highlights both continuities and innovations in the transmission of information from the East (India and China) to the Mediterranean, suggests interpretations on the processes brought to light and opens the door to a further systematic study that will expand the documentary corpus, collect additional material, and also confirm and refine our interpretations. Such an approach is expected to play a fundamental role in the collection of historical ethnopharmacological data and to be applicable to traditions other than the Eastern and Mediterranean ones.

Complete elimination of the negative component of the unipolar atrial electrogram recently proved predictive of lesions transmurality. We prospectively assessed its relevance as a real-time local ablative endpoint for each individual lesion created across the cavotricuspid isthmus (CTI) in order to constitute a line of bidirectionnal block during common atrial flutter (AFL) ablation.Sixty-two consecutive patients underwent common AFL ablation following an electrophysiological approach guided by real-time electrogram modification analysis. In 31 patients (unipolar group), the local ablative endpoint was complete elimination of the negative component of the unipolar atrial electrogram, while the other 31 patients (control group) were treated following our standard approach based on the currently used local ablative endpoint defined by a ≥50% amplitude decrease of the bipolar atrial electrogram. Bidirectional block was achieved in all patients (mean age 67.9 ± 11.5 with 80.6% of men). Mean ablation time (164.3 ± 88.3 seconds vs 332.8 ± 151.5 seconds; P0.001) and mean energy delivery (7.5 ± 4.1 kJ vs 14.2 ± 6 kJ; P0.001) were significantly shorter in the unipolar group compared to the control group. No statistical differences were seen in procedure time (68.5 ± 22.6 min vs 77.5 ± 20.2 min; P = 0.10).Real-time unipolar electrogram modification is a relevant local endpoint during common AFL ablation and leads to a substantial reduction of ablation time and energy delivery compared to a standard ablative approach while displaying a similar short- and long-term success rate.

Ethnopharmacological relevance The relationship between food and medicines has long been investigated and is of crucial importance for the understanding of the development of ethnopharmacological knowledge through time. Hippocrates, considered the Father of Medicine, is credited with an aphorism equating food and medicine. No inquiry has been performed, however, into the collection of texts attributed to Hippocrates and, going beyond, into this statement, which is generally accepted without further examination. A clarification is much needed as the question of the relationship between food and medicines as potent substances are crucial to ethnopharmacology. Materials and methods To verify the validity (if not the authenticity) of the theory on the identity of food and medicine attributed to Hippocrates, we digitized the whole collection of texts ascribed to Hippocrates in the original Greek language (the so-called Hippocratic Collection), which date back from the age of Hippocrates (late 5th century and 4th century BCE) to a more recent time (2nd century CE). On this basis, we extracted and databased all the information related to remedial therapy, that is, their materia medica (vegetable, animal and mineral) and their use(s). We identified both the plant species according to modern up-to-date taxonomy and the medical conditions as precisely as possible. We then screened these plants to discover what their uses were and, going backward in time, we examined (when possible) their native distribution, domestication, possible introduction (in the case of non-native species) and cultivation to determine whether these species had been known for a long time and might have been the object of long-term observation as both foodstuffs and medicines. Results Tabulated data from the Hippocratic Collection revealed that 40% of the remedies in the Collection are made out of only 44 plants. Of this group, 33 species (=75% of the group) were also used for nutritional purposes in Antiquity. Domestication history of these species indicates that humans have long been in contact with them, something that the medical uses of these species confirm, as they are multiple and finely distinguished. A pilot analysis of archeological remains of medicines confirms that textual evidence corresponds to physical evidence, that is, to the practice of medicine. As a consequence, textual information can be accepted as reflecting actual practice. Conclusions Although the pseudo-aphorism according to which food are medicines and medicines are food does not appear as such in the Hippocratic Collection, it aptly expresses a fundamental element of the Hippocratic approach to therapeutics, without being, however, a creation of neither Hippocrates nor his followers and the physicians who practiced a form of medicine in the way of Hippocrates. A vast majority of the core group of plant species used for the preparation of medicines were also consumed as foodstuff. Knowledge and use of these plants probably resulted from a long co-existence in the same environment and also from multiple experiences of trial and error over millennia, whose results accumulated over time and contributed to the formation of the Mediterranean medical tradition.

Ethnopharmacological relevance Ruta is a genus of Rutaceae family. It features mainly shrubby plants, native to the Mediterranean region and present in traditional medicine of this region since Antiquity. The three most diffused species Ruta chalepensis L., Ruta graveolens L., and Ruta montana (L.) L., are morphologically poorly differentiated and were probably interchangeably used during Antiquity. Aim of the study Hippocratic and contemporary medical applications of the Ruta genus in the Mediterranean were compared to check if they result from a continuity of use from the ancient times to nowadays. Results Ruta spp. was mainly employed in medical preparations by Hippocratic physicians as an abortifacient and emmenagogue. In addition to gynaecological conditions, in several treatises of the Corpus Hippocraticum Ruta spp. were also recommended as a specific remedy against pulmonary diseases. Ruta spp. leaves and also roots and seeds, were administered for internal use by Hippocratic physicians after having been soaked in wine or mixed with honey or its derivatives. Contemporary traditional uses of Ruta spp. have been assessed in detail in the whole Mediterranean area. Conclusion Nowadays, Ruta spp. is used to treat different conditions but, as a general rule, the external uses are preferred as the toxicity of the plant is widely acknowledged.

Aims In the setting of congestive heart failure (CHF), atrial fibrillation (AF) ablation can improve clinical status and the left ventricular ejection fraction (LVEF) value. However, the impact of AF ablation on the implantable cardioverter defibrillator (ICD) indication has never been specifically addressed. Methods and results Study subject were six CHF (mean age 61.1 ± 6.9 years, mean LVEF 25.8 ± 7.3%) patients refractory to conventional medical treatment with long-lasting AF unresponsive to external cardioversion. Five patients had an idiopathic dilated cardiomyopathy (DCM) and one had an ischaemic cardiomyopathy (ICM). Their New York Heart Association (NYHA) class was III–IV. Two patients had renal insufficiency. No patient had left ventricular delay. All patients underwent AF ablation. LVEF and NYHA class were dramatically improved in the five DCM patients. New York Heart Association class, but not the LVEF, was improved in the ICM patient. A redo ablative procedure was undertaken in four of five DCM patients and in the ICM patient due to arrhythmia recurrence. Left ventricular ejection fraction and NYHA were improved again in the DCM patients (56 ± 4.4%, I–II, respectively) and led to ICD indication preclusion. The LVEF remained low in the ICM patient (30%) and led to ICD insertion. Sinus rhythm has been stable during the 18.1 ± 5.7 months follow-up period. Conclusion Atrial fibrillation ablation in CHF patients can improve both the clinical status of patients and their LVEF, especially among those affected by DCM. The LVEF improvement has the potential to preclude the indication for a primary prevention ICD insertion.