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Polycythemia vera belongs to myeloproliferative neoplasms, essentially by affecting the erythroblastic lineage. JAK2 alterations have emerged as major driver mutations triggering PV-phenotype with the V617F mutation detected in nearly 98% of cases. That's why JAK2 targeting therapeutic strategies have rapidly emerged to counter the aggravation of the disease. Over decades of research, to go further in the understanding of the disease and its evolution, a wide panel of genetic alterations affecting multiple genes has been highlighted. These are mainly involved in alternative splicing, epigenetic, miRNA regulation, intracellular signaling, and transcription factors expression. If JAK2 mutation, irrespective of the nature of the alteration, is known to be a crucial event for the disease to initiate, additional mutations seem to be markers of progression and poor prognosis. These discoveries have helped to characterize the complex genomic landscape of PV, resulting in potentially new adapted therapeutic strategies for patients concerning all the genetic interferences. [ABSTRACT FROM AUTHOR]

Aim: To define predictors of long-term outcome of a first repeat ablation solely consisting of re-isolation of reconnected pulmonary veins (PVs). Methods: Three hundred seven patients (age 59 ± 9%, 77% males, non-paroxysmal AF 43%) with recurrent AF after first PVI were studied. Re-isolation of reconnected PVs was guided by a circular mapping catheter and 3D mapping system using RF ablations. A PV was defined as "triggering" in case of spontaneous ectopy or AF paroxysms originating from the PV. Results: After a mean follow-up of 5.05 ± 2.21 years, 194 (63.2%) patients (73.0% in PAF vs 50.4% in non-PAF, log Rank <0.001) were free from AF. A "triggering" PV was present in 48 (15.6%) during the first PVI and in 52 (16.9%) at repeat. Independent predictors of recurrence were a non-PAF type (HR: 1.814, 95%CI: 1.090 - 3.018, p=0.022) and early recurrence (≤ 3 months) after first PVI (HR: 1.632, 95%CI: 1.091 - 2.443, p=0.017) while a "triggering" PV at first or repeat was a predictor of good outcome (HR: 0.574; 95%CI: 0.344 - 0.959; p=0.034) in the multivariable analysis. Conclusions: A repeat ablation solely consisting of re-isolation of reconnected PVs results in a high degree of long-term AF freedom, especially in PAF and in case of a PV trigger at index or repeat. Patients with non-PAF or experiencing early AF recurrence after first PVI are less responsive. [ABSTRACT FROM AUTHOR]

Triggering Pulmonary Veins and Recurrence After Ablation. Purpose: To identify procedural parameters predicting recurrence of atrial fibrillation (AF) after a first circumferential pulmonary vein isolation (CPVI). Methods: One hundred seventy-one patients undergoing CARTO-guided CPVI for recurrent AF with a left atrial (LA) diameter <45 mm were studied. Follow-up (symptoms and 7-day Holter) was performed at 1 and 3 months and every 3 months thereafter. Clinical and procedural characteristics between successful patients and patients undergoing repeat ablation were compared. In addition, procedural parameters of the first procedure were compared with parameters during repeat ablation. Results: After first CPVI, 80% of patients were free of AF without antiarrhythmic drugs after a follow-up (FU) of 28 ± 11 months (N = 136). Thirty-five patients (20%) had recurrence of AF of which 25 underwent repeat ablation (N = 25). Clinical characteristics did not differ between the successful and repeat group. A triggering vein during the index procedure was significantly more observed in the repeat group (56% vs 11%, P < 0.001). At repeat ablation, 2.6 ± 1.2 veins per patient were reconnected. Whereas there was no preferential reconnecting PV, all PVs triggering at index were reconnected (100%). Conclusions: (1) In patients with symptomatic recurrent AF, the presence of a triggering pulmonary vein during ablation is a paradoxical predictor for AF recurrence after PV isolation. (2) The consistent finding of reconnection of the triggering PV at repeat ablation, suggests that, in these patients, the triggering PV is the culprit vein and that reconnection invariably results in clinical AF recurrence. (3) The present study advocates a strategy of even more stringent PV isolation in case of a triggering PV. (J Cardiovasc Electrophysiol, Vol. 21, pp. 381–388, April 2010) [ABSTRACT FROM AUTHOR]

Background Triggers from thoracic veins have been implicated not only in the initiation, but also in the perpetuation of paroxysmal atrial fibrillation (PAF). To investigate their role we studied the distribution and stability of dominant frequencies (DFs) during PAF and the response to isolation of the triggering pulmonary vein (PV). Methods and Results Triggering structures inducing PAF were identified during isoproterenol challenge in 26 patients (15 males, 55 ± 8.5 years). During sustained PAF, sequential recordings were made with a decapolar circular mapping catheter from each PV and the left atrial posterior wall (LAPW), together with coronary sinus (CS) and right atrium (RA) recordings. DF was determined using fast Fourier transformation. Recordings were repeated after ≥15 minutes of PAF. Radiofrequency ablation was directed first at the triggering PVs. PAF initiated from the PVs in 24 patients and from RA in two. There was a significant frequency gradient from the triggering structure to the PVs, CS, LAPW, and RA (P < 0.0001). During the second recording, DF decreased at all sites (P < 0.02), but the frequency gradient remained unchanged. Despite isolation of the triggering PV, PAF continued in 53% of patients, although DF measured in the CS was lower. AF termination occurred with contralateral PV isolation in half of the remaining patients and further AF slowing was noted in the rest. Conclusions Triggering structures harbor the fastest activity during sustained PAF pointing to their leading role in arrhythmia perpetuation. However, nontriggering PVs also seem to contribute to PAF maintenance. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) using the CARTO 3D mapping system is a common approach for pulmonary vein isolation to treat atrial fibrillation (AF). Linkage between CARTO procedural data and patients' electronical health records (EHR) provides an opportunity to identify the ablation-related parameters that would predict AF recurrence. The objective of this study is to assess the incremental accuracy of RFA procedural data to predict post-ablation AF recurrence using machine learning model. Procedural data generated during RFA procedure were downloaded from CARTONET and linked to deidentified Mercy Health EHR data. Data were divided into train (70%) and test (30%) data for model development and validation. Automate machine learning (AutoML) was used to predict 1 year AF recurrence, defined as a composite of repeat ablation, electrical cardioversion, and AF hospitalization. At first, AutoML model only included Patients' demographic and clinical characteristics. Second, an AutoML model with procedural variables and demographical/clinical variables was developed. Area under receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI) were used to compare model performances using test data. Among 306 patients, 67 (21.9%) patients experienced 1-year AF recurrence. AUROC increased from 0.66 to 0.78 after adding procedural data in the AutoML model based on test data. For patients with AF recurrence, NRI was 32% for model with procedural data. Nine of 10 important predictive features were CARTO procedural data. From CARTO procedural data, patients with lower contact force in right inferior site, long ablation duration, and low number of left inferior and right roof lesions had a higher risk of AF recurrence. Patients with persistent AF were more likely to have AF recurrence. The machine learning model with procedural data better predicted 1-year AF recurrence than the model without procedural data. The model could be used for identification of patients with high risk of AF recurrence post ablation. [ABSTRACT FROM AUTHOR]

Background: Whether dissociated firing (DiFi) in isolated pulmonary veins (PVs) implies arrhythmogenicity of the particular PVand, therefore, a better outcome of PV isolation (PVI) for paroxysmal atrial fibrillation (PAF) is debated.Methods: Thirty-one patients undergoing their first PVI for PAF were studied. Isoproterenol was infused for induction, and the triggering PV was identified. During sustained PAF, sequential recordings were made with a decapolar circular mapping catheter from each PV. The dominant frequency (DF) was determined using fast Fourier transformation. Spontaneous DiFi was monitored for 30 min after PVI.Results: PAF was triggered by the PVs in all patients. Fourteen (45 %) patients had DiFi after PVI in at least one PV. It was recorded most commonly from the left upper (84 %) and lower (67 %), less commonly from the right upper (31 %) PV. Out of the 23 PVs with DiFi, 13 (57 %) showed sporadic ectopic beats while 10 (44 %) had sustained ectopic rhythm or isolated tachycardia. There was no difference in size between PVs with or without DiFi (5.9±1.2 vs. 5.6±1.0 cm ostial perimeter, p=0.40). Triggering PVs more commonly showed any DiFi, compared to nontriggering PVs (68 vs. 27 %, p=0.003) and more commonly had sustained DiFi (53 vs. 0 %, p<0.001). During PAF PVs with any DiFi showed faster maximal DF compared to PVs without DiFi (7.1±1.3 vs. 5.9±1.1 Hz, p=0.001). Higher maximal DF was recorded in PVs with sustained versus sporadic DiFi versus PVs without DiFi (7.5 ±0.9 vs. 6.8±1.6 vs. 5.9±1.1 Hz, respectively, p=0.002). Patients with DiFi after PVI had a longer mean time to recurrent PAF compared to those without DiFi (52 vs. 32 months, p=0.048).Conclusions: Dissociated firing in isolated PVs is associated with their role in the initiation and maintenance of PAF. [ABSTRACT FROM AUTHOR]

Is SIPVI Sufficient for Focally Triggered Paroxysmal Atrial Fibrillation? Introduction: Selective ipsilateral pulmonary vein isolation (SIPVI) has shown comparable efficacy in focal triggered atrial fibrillation (AF) versus isolation of all pulmonary veins (PVs), yet the sufficiency for such an ablation strategy to all patients is unclear. This study sought to identify a subgroup of patients for SIPVI and a subgroup of patients for bilateral PV isolation (BiPVI) with long-term success by comparing the clinical efficacy of SIPVI and BiPVI on PV-triggered AF. Methods and Results: One hundred and forty-two patients (106 males; mean age 51 ± 13 years) with focal PV triggered paroxysmal AF (PAF) were studied. Seventy patients underwent SIPVI and 72 patients underwent BiPVI. After the first ablation, 44 patients (44/70) in the SIPVI group and 54 patients (54/72) in the BiPVI group were free of AF without antiarrhythmic drugs, after a follow-up period of 36 ± 12 months (log-rank test P = 0.1594). In patients younger than 50 years of age with a left atrium (LA) diameter <40 mm, SIPVI had a high success rate (15/18, 83%) of freedom from AF. However, for patients aged ≥50 years with an LA diameter ≥40 mm, 10 of the 12 patients in the SIPVI group and only 5 of the 15 patients in the BiPVI group had a recurrence of AF (log-rank test P = 0.0173). Conclusions: For focally triggered PAF, in patients aged <50 years with an LA diameter <40 mm, SIPVI of triggering PV had a high success rate of freedom from AF. However, in patients aged ≥50 years with an LA diameter ≥40 mm, BiPVI achieved a higher success rate. (J Cardiovasc Electrophysiol, Vol. 23, pp. 130-136, February 2012) [ABSTRACT FROM AUTHOR]

The rapid evolution of anti-cancer therapy (including chemotherapy, targeted therapy, and immunotherapy) in recent years has led to a more favorable efficacy and safety profile for a growing cancer population, and the improvement of overall survival and reduction of morbidity for many cancers. Anti-cancer therapy improves outcomes for cancer patients; however, many classes of anti-cancer therapy have been implicated in the induction of bullous dermatologic adverse events (DAE), leading to reduced patient quality of life and in some cases discontinuation of life-prolonging or palliative therapy. Timely and effective management of adverse events is critical for reducing treatment interruptions and preserving an anti-tumor effect. Bullous DAE may be limited to the skin or have systemic involvement with greater risk of morbidity and mortality. We present the epidemiology, diagnosis, pathogenesis, and management of bullous DAE secondary to anti-cancer therapies to enable clinicians to optimize management for these patients. [ABSTRACT FROM AUTHOR]

The operation of the photovoltaic (PV) system under partial shading conditions (PSC) is complicated since the output characteristic of the PV system is profoundly affected by the heterogeneous irradiance of PSC. This paper proposes a dynamic reconfiguration framework to tackle PSC in the PV array. Continuous operation of the dynamic PV array reconfiguration under cloud-induced partial shading is considered by developing an emulator of the moving cloud. In addition, the Particle Swarm Optimization and Rao algorithms are improved to obtain the optimal PV array configuration under PSC. The operation of switching is enhanced by simultaneously considering the total switching times and the operation of highly active switches. The simulation results on the 9 × 9 PV array demonstrate the effectiveness of the proposed framework in terms of reducing the number of local maximum power points on the power-voltage characteristic, enhancing power output, and relieving stress on the switching operation of the PV array under different PSC. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is an autoimmune disorder resulting from the interaction between autoantibodies and desmoglein. Here, we report a case of PV developed after 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). The harmful and deleterious effects of UV radiation on the onset, during course, and perpetuation of PV have been observed for decades. Correlation between reactive oxygen species (ROS) and PV have also been reported. Oxidative proteins, which are modified by ROS, and subsequent production of antibodies by immune system seem to be responsible for PV developed following ALA-PDT. We emphasize that ALA-PDT should be added to the list of possible factors triggering PV and this condition should be considered if blistering arises following ALA-PDT. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the frequency and functionality of DCs and its associated stimulatory and inhibitory markers in the pathogenesis of PV Active PV patients (n = 30) having both skin and oral lesions, and 30 healthy controls were recruited in the study. The frequency of DCs was determined by flow cytometry followed by the primary culture by using recombinant IL-4 (250 IU/ml) and GM-CSF (600 IU/ml). The culture supernatant was used for ELISA. RNA was isolated from sorted DCs and used for the mRNA expression of DC-associated stimulatory (CD40 and CD80) and inhibitory (PSGL1 and ILT3) markers. Tissue localization of Langerhans cells was done by immunohistochemistry. In this study, altered frequency of myeloid DC (mDC) and plasmacytoid DC (pDC) was seen in the circulation of PV patients. The primary culture of patient-derived DCs showed anomalous cytokine profiling. In the culture supernatant of DCs, elevated levels of TNF-ɑ and IL-12 were detected in PV patients. Meanwhile, reverse trend was found in the case of IFN-ɑ and IL-10 cytokine levels. Similarly, a discrepancy in the expression of DC-associated stimulatory (CD40 and CD80) and inhibitory (PSGL1 and ILT3) markers suggested their possible involvement in the immunopathogenesis of PV. An elevated number of tissue localizing Langerhans cells was also observed in the perilesional skin. This study indicates the distorted frequency and functionality of DCs in the immunopathogenesis of PV. Targeting these functional markers in the future may generate novel therapeutic options for better management of PV. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV), in association with malignancy of the rectum, is a very rare presentation. We present here a case of a 58-year- old woman presenting with atypical skin eruptions in the peristomal area, which gradually progressed to her entire body. These lesions were later diagnosed to be PV. She developed these lesions in her postoperative period following an anterior resection with a covering ileostomy for her rectal malignancy. She had received neoadjuvant chemo+radiotherapy for her malignancy. [ABSTRACT FROM AUTHOR]

Introduction: Phase singularity (PS) mapping provides additional insight into the AF mechanism and is accurate in identifying rotors. The study aimed to evaluate the feasibility of PS mapping in identifying AF rotors using data obtained from an automatic ultra‐rapid high‐resolution mapping system with a high‐density mini‐basket catheter. Methods: Twenty‐three pigs underwent rapid right atrial (RA) pacing (RAP 480 bpm) for 5 weeks before the experiment. During AF, RA endocardial automatic continuous mappings with a mini‐basket catheter were generated using an automatic ultra‐rapid mapping system. Both fractionation mapping and waveform similarity measurements using a PS mapping algorithm were applied on the same recording signals to localize substrates maintaining AF. Results: Seventeen (74%) pigs developed sustained AF after RAP. Three were excluded because of periprocedural ventricular arrhythmia and corrupted digital data. RA fractionation maps were acquired with 6.17 ± 4.29 minutes mean acquisition time, 13768 ± 12698 acquisition points mapped during AF from 581 ± 387 beats. Fractionation mapping identified extensively distributed (66.7%) RA complex fractionated atrial electrogram (CFAE), whereas the nonlinear analysis identified high similarity index (SI > 0.7) parts in limited areas (23.7%). There was an average of 1.67 ± 0.87 SI sites with 0.43 ± 0.76 rotor/focal source/chamber. AF termination occurred in 11/16 (68.75%) AF events in 14 pigs during ablation targeting max CFAE. There was a higher incidence of rotor/focal source at AF termination sites compared with non‐AF termination sites (54.5% vs 0%, P = 0.011). Conclusions: The data obtained from ultra‐rapid high‐density automatic mapping is feasible and effective in identifying AF rotors/focal sources using PS technique, and those critical substrates were closely related to AF procedural termination. [ABSTRACT FROM AUTHOR]

Introduction: Both isoproterenol (Iso) and adenosine (Ado) are used to induce atrial fibrillation (AF) in the electrophysiology lab. However, the utility of Ado has not been systematically established. Objective: The purpose of this study was to compare Ado to Iso for the induction of paroxysmal AF. Methods: Forty patients (16 women; mean age, 60 ± 12 years) with paroxysmal AF, presenting for ablation were prospectively included of whom 36 (90%) received Ado (18‐36 mg) and/or Iso (3‐20 µg/min incremental dose) in a randomized order (26 [72%] received both drugs). Results: AF was induced with Iso in 15 of 32 (47%) and with Ado in 12 of 30 (40%) patients (P = 0.9). Iso‐triggered AF started from the left pulmonary veins (PVs) in 11 of 15 (73%), from the right PVs in 3 of 15 (20%), and from the coronary sinus (CS) in 1 of 15 (7%) cases. Ado‐induced AF episodes originated from the left PVs in 6 of 12 (50%), from the right atrium (RA) in 4 of 12 (33%), and from the CS in 2 of 12 (17%) cases. Altogether, Iso‐induced AF was more likely initiated from the PVs (93%) compared with Ado (50%) (P = 0.02). Ado‐induced non‐PV triggers were not predictive of arrhythmia recurrence after PV isolation. Conclusion: Ado much more frequently induces non‐PV triggers, especially from the RA. The clinical significance of these foci, however, is questionable. [ABSTRACT FROM AUTHOR]

Aims: The predictive value of induction studies after catheter ablation for atrial fibrillation (AF) is still debatable. To date, these studies have not been implemented in patients after cryoballoon (CB) ablation. Our aim was to analyse the clinical value of AF induction in patients treated by second generation CB for paroxysmal AF.Methods and results: Seventy patients underwent at first an isoproterenol challenge after pulmonary vein (PV) isolation to assess AF induction and early PV reconnections (EPVR). Patients without EPVR were evaluated for premature atrial contraction (PAC) induction; atrial ectopy was considered frequent (PAC+) if >1/10 cycles or >6/min. After restitution of baseline heart rate, rapid atrial pacing (RAP) was performed on all patients. AF induction by isoproterenol occurred only in 3/70 (4%) patients of whom 2/3 (66%) patients with an EPVR of a triggering vein. In the 62 patients without EPVR, PAC+ occurred in 17 patients (27%). RAP could induce AF in 23/70 (33%) patients. At a mean follow-up of 13.5 months, there were 11/70 (16%) AF recurrences. There was no significant difference in the AF recurrence rate between RAP inducible vs. non-inducible patients (log-rank P = 0.33). A 41% recurrence rate (7/17 patients) was seen in the PAC+ group with significantly different AF-free survival for PAC+ vs. PAC- patients (log rank P < 0.0001). PAC+ was the only independent determinant to predict AF recurrence after multivariate analysis.Conclusion: PAC occurrence in response to isoproterenol could predict AF recurrence after PV isolation by CB, while RAP showed no prognostic implication. [ABSTRACT FROM AUTHOR]

Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO). Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide (LPS) in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1b (IL-1b), markers of oxidative stress and NADPH oxidase 2 (Nox2) in the hippocampus. In addition, LPS exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived reactive oxygen species (ROS) production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice. [ABSTRACT FROM AUTHOR]

Pemphigus Vulgaris (PV) is a blister causing autoimmune disease that is continually being studied because of its devastating symptomology and life-threatening effects on patients afflicted with the disease. There is a sense of urgency in finding better treatment options for PV patients and an even greater emphasis placed on diagnosing the disease in its earliest stages in order to improve its prognosis. The purpose of this paper is to provide a thorough presentation of pemphigus vulgaris, by discussing its genetics, prevalence, physiological mechanisms, pathogenesis, diagnostic and monitoring techniques, and treatments, in order to better equip clinicians with the current information on the disease and to prompt interest in future research on identifying potential environmental triggers. [ABSTRACT FROM AUTHOR]

Background Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 ( CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. Objectives To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. Methods CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis ( GPP). Novel variants were evaluated for their effect on nuclear factor ( NF)-κB signalling. Results Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-κB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-κB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36 RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. Conclusions These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and represents a major burden to health care systems. Atrial fibrillation is associated with a 4- to 5-fold increased risk of thromboembolic stroke. The pulmonary veins have been identified as major sources of atrial triggers for AF. This is particularly true in patients with paroxysmal AF but not always the case for those with long-standing persistent AF (LSPAF), in which other locations for ectopic beats have been well recognized. Structures with foci triggering AF include the coronary sinus, the left atrial appendage (LAA), the superior vena cava, the crista terminalis, and the ligament of Marshall. More than 30 studies reporting results on radiofrequency ablation of LSPAF have been published to date. Most of these are observational studies with very different methodologies using different strategies. As a result, there has been remarkable variation in short- and long-term success, which suggests that the optimal ablation technique for LSPAF is still to be elucidated. In this review we discuss the different approaches to LSPAF catheter ablation, starting with pulmonary vein isolation (PVI) through ablation lines in different left atrial locations, the role of complex fractionated atrial electrograms, focal impulses and rotor modulation, autonomic modulation (ganglionated plexi), alcohol ablation, and the future of epicardial mapping and ablation for this arrhythmia. A stepwise ablation approach requires several key ablation techniques, such as meticulous PVI, linear ablation at the roof and mitral isthmus, electrogram-targeted ablation with particular attention to triggers in the coronary sinus and LAA, and discretionary right atrial ablation (superior vena cava, intercaval, or cavotricuspid isthmus lines). [ABSTRACT FROM AUTHOR]

Dissociated Pulmonary Vein Activity for Paroxysmal Atrial Fibrillation Background The role of dissociated pulmonary vein (DPV) activity after pulmonary vein isolation (PVI) is still poorly defined. We evaluated electrophysiological features and clinical impact on long-term outcome of DPV activity. Methods A total of 243 patients (mean age 63 ± 11 years; 63% males) undergoing PVI for paroxysmal atrial fibrillation (AF) were included. DPV activity was defined as a residual low frequency irregular PV rhythm. Patients were divided into Group 1 (presence of DPV activity; n = 65) or Group 2 (absence of DPV activity; n = 178). Results Of 936 isolated PVs, 112 PVs (12%) showed DPV activity. DPV activity was observed more frequently in PVs identified as AF triggers (P = 0.026). During follow-up (mean 12 ± 7 months), 15 of 65 patients of Group 1 (23%) and 57 of 178 patients of Group 2 (32%) had an arrhythmia recurrence (P = 0.23). At linear regression analysis, no independent predictor for clinical recurrence was identified. During the repeat ablation, 62 of 72 patients (86%) showed a recovered PV conduction without difference between the 2 groups. Clinically, all patients of Group 1 with PV reconnection (n = 13/15) had a recurrence of paroxysmal AF. In Group 2, 5 of 52 patients with reconnected PV developed non-PV related arrhythmias. Conclusion DPV activity occurred in 12% of PVs after PVI and was observed more frequently in PVs identified as AF triggers. DPV activity was not predictive for AF recurrence during follow-up. PV-left atrium reconnection involving PVs with DPV activity leads to AF. [ABSTRACT FROM AUTHOR]

A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated. [ABSTRACT FROM AUTHOR]

Radiofrequency Applications for Spontaneous Dissociated Pulmonary Vein Activity Background The aim is to evaluate the efficacy of additional radiofrequency ablation (RFCA) for spontaneous dissociated pulmonary vein activity (DPV-spike) after PV isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). Methods One hundred fifty-two consecutive patients with paroxysmal AF referred for RFCA were enrolled. When DPV-spike was documented after PVI, we randomly assigned these patients to receive additional RFCA for DPV-spike or only PVI. We divided them into 4 groups: 87 patients without DPV-spike after PVI (No-spike group), 31 without DPV-spike after additional RFCA (Successful group), 8 with remaining DPV-spike after additional RFCA (Unsuccessful group), and 26 with DPV-spike after only PVI (Spike group). AF recurrence was evaluated among the 4 groups. Results After PVI, DPV-spike was documented in 87 PVs (14%) from 65 patients. During 16 ± 9 months of follow-up, the incidence of the freedom from AF was significantly higher in the No-spike group than that in the Spike group and Unsuccessful group (P < 0.05), and tended to be higher in the Successful group than that in the Spike group and Unsuccessful group (P = 0.08 and 0.11, respectively). In a multivariate analysis, the remaining PV-spike after ablation was an independent predictor of AF recurrence (HR 2.44; CI 1.10-5.43, P < 0.05). No major complications including PV stenosis were observed during the follow-up. Conclusions DPV-spike after PVI may be associated with higher electrical activity within the PVs and may be one of the risk factors for AF recurrence. Additional RFCA for DPV-spike was effective to reduce the AF recurrence after PVI. [ABSTRACT FROM AUTHOR]

Background: Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Methods: Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca2+ homeostasis on the egress programme. Results: A steady increase in cytoplasmic free Ca2+ is found to precede parasite egress. This increase is independent of extracellular Ca2+ for at least the last two hours of the cycle, but is dependent upon Ca2+ release from internal stores. Intracellular BAPTA chelation of Ca2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca2+-ATPase accelerate parasite egress, indicating that Ca2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. Conclusions: The parasite egress programme requires intracellular free Ca2+ for egress initiation, vacuole swelling, and host cell cytoskeleton digestion. The evidence that parasitophorous vacuole swelling, a stage of unaffected egress, is dependent upon a rise in intracellular Ca2+ suggests a mechanism for ionophore-inducible egress and a new target for Ca2+ in the programme liberating parasites from the host cell. A regulatory pathway for egress that depends upon increases in intracellular free Ca2+ is proposed. [ABSTRACT FROM AUTHOR]

Aims: To define predictors of long-term outcome of a first repeat ablation solely consisting of re-isolation of reconnected pulmonary veins (PVs)., Methods: Three hundred seven patients (age 59 ± 9%, 77% males, non-paroxysmal AF 43%) with recurrent AF after first PVI were studied. Re-isolation of reconnected PVs was guided by a circular mapping catheter and 3D mapping system using RF ablations. A PV was defined as "triggering" in case of spontaneous ectopy or AF paroxysms originating from the PV., Results: After a mean follow-up of 5.05 ± 2.21 years, 194 (63.2%) patients (73.0% in PAF vs 50.4% in non-PAF, log Rank <0.001) were free from AF. A "triggering" PV was present in 48 (15.6%) during the first PVI and in 52 (16.9%) at repeat. Independent predictors of recurrence were a non-PAF type (HR: 1.814, 95%CI: 1.090 - 3.018, p=0.022) and early recurrence (≤ 3 months) after first PVI (HR: 1.632, 95%CI: 1.091 - 2.443, p=0.017) while a "triggering" PV at first or repeat was a predictor of good outcome (HR: 0.574; 95%CI: 0.344 - 0.959; p=0.034) in the multivariable analysis., Conclusions: A repeat ablation solely consisting of re-isolation of reconnected PVs results in a high degree of long-term AF freedom, especially in PAF and in case of a PV trigger at index or repeat. Patients with non-PAF or experiencing early AF recurrence after first PVI are less responsive.

. (J Cardiovasc Electrophysiol, Vol. 22, pp. 638-646, June 2011) [ABSTRACT FROM AUTHOR]

In the article the authors reflect on the ablation of paroxysmal atrial fibrillation (PAF). Research shows that pulmonary vein (PV) foci are responsible for PAF in a number of patients with arrhythmias. They review De Greef and colleagues article "Triggering Pulmonary Veins: A Paradoxical Predictor for Atrial Fibrillation Recurrence After PV Isolation," which discusses PV isolation and ablation techniques. Robotic innovations and adenosine use for dormant PV reconnection are also discussed.

Ingenol mebutate is a recently approved topical agent for the treatment of actinic keratosis. Its most common adverse effects are transient local skin reactions. We report a 63-year-old white man who presented with a red-brownish crusted plaque involving the dorsum of his nose and an eroded area on his lower lip, which appeared soon after topical application of ingenol mebutate gel. Clinical, histological and immunopathological features were consistent with a diagnosis of pemphigus vulgaris ( PV). To our knowledge, this is the first report of relapse of PV after topical application of ingenol mebutate gel. The temporal relationship between the application of the drug and the outbreak of PV supports the involvement of this agent in triggering the disease. It is plausible that ingenol mebutate may have induced the disease by its action on the production of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Electrophysiologically demonstrated complete conduction block at the level of the veno-atrial junction is preferable as the endpoint of pulmonary vein (PV) ablation rather than circumferential periostial radiofrequency delivery. Knowledge of the individual anatomy of the PVs and the left atrium (LA), appropriate positioning of circular mapping catheters, and the electrophysiology of PV activation in addition to effective ablation tools is necessary to achieve this endpoint. Additional unnecessary ablation and possibly complications can be avoided by the recognition of non-PV myocardial contributions to PV electrograms. The posterior wall of the LA appendage contributes far-field electrograms to recordings from all left superior PVs (LSPV), the low lateral LA to 80% of left inferior PV (LIPV) recordings and the superior vena cava to 23% of right superior PV (RSPV) recordings. Each of these far-field components can be recognized in sinus rhythm as well as during ongoing atrial fibrillation. Finally, the creation of temporally stable and definitive PV isolation remains a currently unsolved problem. [ABSTRACT FROM PUBLISHER]

The JAK2V617F variant constitutes a genetic alteration of higher frequency in BCR/ABL1 negative chronic myeloproliferative neoplasms, which is caused by a substitution of a G ˃ T at position 1849 and results in the substitution of valine with phenylalanine at codon 617 of the polypeptide chain. Clinical, morphological and molecular genetic features define the diagnosis criteria of polycythemia vera, essential thrombocythemia and primary myelofibrosis. Currently, JAK2V617F is associated with clonal hematopoiesis, genomic instability, dysregulations in hemostasis and immune response. JAK2V617F clones induce an inflammatory immune response and lead to a process of immunothrombosis. Recent research has shown great interest in trying to understand the mechanisms associated with JAK2V617F signaling and activation of cellular and molecular responses that progressively contribute to the development of inflammatory and vascular conditions in association with chronic myeloproliferative neoplasms. Thus, the aim of this review is to describe the main genetic, hematological and immunological findings that are linked to JAK2 variant signaling in chronic myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

Vagal Denervation After Pulmonary Vein Ablation. Introduction: Pulmonary vein (PV) isolation has proven to be an effective therapy for atrial fibrillation (AF). However, clinical evidence suggests that suppression of AF after PV isolation could not be fully attributed to the interruption of electrical conduction in and out of the PVs. Furthermore, little is known regarding the effects of ablation around the PVs on the atrial electrophysiological properties. We aimed to study the changes in atrial response to vagal stimulation (VS) after PV ablation (PVA). Methods: We studied 11 adult mongrel dogs under general anesthesia. Bilateral cervical sympathovagal trunks were decentralized. Propranolol was given to block sympathetic effects. Multipolar catheters were placed into right atrial appendage (RAA), distal and proximal coronary sinus (CSD, CSP), and left atrial free wall (LAFW). PVA was performed via trans-septal approach. Atrial effective refractory period (AERP) and vulnerability window (VW) of AF were measured with and without VS before and after ablation to isolate the PVs. Results: After ablation, AERP shortening in response to VS significantly decreased in the left atrium (43.64 ± 21.57 vs 11.82 ± 9.82 msec, P < 0.001 at LAFW; 50.91 ± 26.25 vs 11.82 ± 14.01 msec, P < 0.001 at CSP; 50 ± 31.94 vs 17.27 ± 20.54 msec, P < 0.005 at CSD), while the response to VS did not change significantly at RAA (58.18 ± 28.22 vs 50.91 ± 22.12 msec, P = 0.245). After ablation, atrial fibrillation VW during VS narrowed (20.63 ± 11.48 vs 5.63 ± 8.63 msec, P < 0.03 at LAFW; 26.25 ± 12.46 vs 5.00 ± 9.64 msec, P = 0.001 at CSP; 28.75 ± 18.47 vs 6.88 ± 7.53 msec, P < 0.02 at CSD, and 33.75 ± 24.5 vs 16.25 ± 9.91 msec, P = 0.03 at RAA). Conclusions: Ablation around the PV ostia diminishes left atrial response to VS and decreases the atrial VW. The attenuated vagal response after ablation may contribute to the suppression of AF. (J Cardiovasc Electrophysiol, Vol. 16, pp. 1-6, August 2005) [ABSTRACT FROM AUTHOR]

Reports on the development of nonpharmacologic therapies for atrial fibrillation (AF) in people who are persistently symptomatic. Prevention of AF through physiologic or overdrive pacing; Use of antitachycardia pacing or atrial defibrillation, delivered automatically or triggered manually, to restore sinus rhythm; Intention of treatment to eliminate AF altogether in the third approach; Treatment approaches that are only palliative.

Abstract Background Pemphigus vulgaris is a potentially life-threatening disease characterized by cutaneous and mucosal blistering. Systemic corticosteroids remain the mainstay of therapy, transforming an invariably fatal disease into one with a mortality that is now less than 10%. Nevertheless, oral lesions are often recalcitrant and corticosteroid therapy can provoke adverse effects. Objective To determine whether two different regimens of systemic corticosteroid therapy based on prednisone gave different benefits. Method We examined two different regimens of systemic corticosteroid therapy based on prednisone in an open study. Ten patients (group A) were treated with systemic corticosteroids, in a therapeutic protocol made up of orally administered prednisone. Ten matched patients (group B) were treated with systemic corticosteroids alternating a pulse of intravenous betamethasone with orally administered prednisone. Results and conclusions The pulse protocol appeared to have some advantages both in a shorter time to resolution of symptoms and oral lesions, and in terms of minor adverse effects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of structured habituation training HT for movement provoked vertigo PV secondary to unilateral peripheral hypofunction in a 16 year old patient who had sustained a severe TBI. Treatment of PV with severe TBI patients can be quite different from other patients with vestibular deficits because of the physiological, behavioural and cognitive sequelae of brain trauma. A single subject experimental paradigm using an ABA protocol was used to assess efficacy of HT. The data were submitted to C statistic analysis. The transformed data were submitted to combined visual and statistical analysis by the celeration line with a directional one tailed test and the two standard deviation band method. Significant change in duration from sitting to supine without triggering vertigo was found between baseline phase A and structured HT phase B and was maintained for 1 month after the end of treatment. This single case experiment demonstrates successful structured HT for PV for a 16 year old severe TBI patient. Important clinical decisions time of introduction of treatment, type of activity, pacing, frequency, intensity, repetition, support and education necessary to achieve optimal resolution of PV with HT in severe TBI patients are discussed. [ABSTRACT FROM AUTHOR]