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Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.

Background: Ventricular tachycardia (VT) is common after myocardial infarction. Catheter ablation for VT is invasive, tedious and complicated, and success rates are unsatisfactory. We have previously established a workflow to treat ischemic scar with pencil-beam scanning proton therapy. Long-term follow-up data on proton beam ablation of ischemic scar is lacking. Objective: To evaluate the safety of targeted proton beam therapy of ischemic scar in a porcine model. Methods: An anterior myocardial ischemic scar was created in 14 domestic swine through temporary balloon occlusion and subsequent reperfusion of the left anterior descending artery. Using delayed gadolinium enhanced MRI, supported by high-definition voltage mapping, the resulting scar was contoured and transferred to a cardiac 4D CT for treatment planning. A part of the scar was selected as target volume and treated with 40 Gy (n = 12) or 30 Gy (n = 2). Implantable loop recorders (ILR) were inserted to monitor for arrhythmias. Cardiac MRI was performed every 4 weeks during a follow-up of up to 24 weeks. Results: No acute complications occurred during treatment. Four animals died suddenly, which is not significantly different from the mortality previously seen in non-infarcted swine treated with cardiac proton beam therapy (log rank test, p = 0.33). The ILR showed monomorphic VT as initial rhythm in all cases. All ventricular arrhythmias occurred between 8 and 14 weeks after treatment. Gross pathology showed no specific findings and histology showed patchy fibrosis in the treated area. Left ventricular ejection fraction (LVEF) was stable in serial cardiac MRIs. For animals with follow-up ≥ 12 weeks, LVEF was 49 ± 5 % at baseline and 51 ± 6 % at last follow-up (p = 0.24). Summary: A transient period of increased arrhythmogenicity was observed between 8 and 14 weeks after treatment, possibly due to ablative tissue transformation. These arrhythmias would be covered by an implantable cardioverter-defibrillator in a clinical scenario. Although it has previously been shown that extensive irradiation of the left ventricular myocardium has the potential to impair LVEF, no adverse effect on LVEF was seen in our targeted proton beam treatment during a follow-up of up to 24 weeks. Conclusion: Targeted proton beam therapy of ischemic myocardial scar is feasible without functional impairment. A transiently increased arrhythmia burden should be taken into account when evaluating this technique in a clinical setting. [ABSTRACT FROM AUTHOR]

Aims: Female physicians are underrepresented in invasive electrophysiology (EP) for multiple reasons. Despite an increasing focus on the topic, it is unclear what aspects are predominant., Methods and Results: We conducted a survey on career paths of current or former EP fellows in Germany to elucidate how gender and family affected their careers. 231 fellows (24.2% female) were invited. 110 participants completed the survey (30.9% female, mean age 41.0 ± 5.0 years, and 79.1% with children). Female and male participants with children reported similar career goals and achievements before parenthood, but afterwards women changed their career paths more often. Major reasons were personal priorities followed by lack of flexibility at work and at home. Women covered the majority of childcare. At the time of the survey, 80.0% of women and 96.4% of men with a former career goal of invasive EP were active in invasive EP. Independent of age, women were in lower-level positions, had accomplished fewer professional achievements, were less satisfied with their work and had fewer children. 56.5% of women did not feel supported by their employers regarding family issues. 82.6% reported there was no satisfactory day care. 69.6% were unable to continue to follow their career during pregnancy, mostly due to restrictions by employers (75.0%). Dedicated policies for pregnant workers or support programmes were scarce., Conclusion: Beside the distribution of childcare at home, lack of flexibility and support by employers as well as working and fluoroscopy restrictions during pregnancy hamper women in EP and should be addressed., Competing Interests: Conflict of interest: J.M.-L. received lecture honorary, travel grants and/or a fellowship grant from Abbott, Biotronik, Boston Scientific, Medtronic and Zoll, outside the submitted work. H.A.K.H. received lecture honorary and/or a fellowship grant from AstraZeneca, Boston Scientific and Zoll, outside the submitted work. J.E. received a fellowship grant from Biotronik outside the submitted work. E.A. has no conflicts to declare. N.K. received lecture honorary from Abbott outside the submitted work. S.H. received a fellowship grant from Boston Scientific and lecture honorary from Abbott and Medtronic, outside the submitted work. D.D. received lecture honorary, travel grants and/or a fellowship grant from Abbott, Astra Zeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Medtronic, Microport, Pfizer, Sanofi and Zoll, outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Boda-Heggemann reports consulting fees from EBAMed SA and a research grant from Elekta, outside the submitted work. Dr. Andratschke reports grants from SPHN Imaging – Swiss National Funds, from Clinical Research Priority Program University of Zurich, during the conduct of the study; personal fees from Debiopharm, personal fees from Astrazeneca, grants, personal fees and non-financial support from ViewRay, grants from Brainlab, outside the submitted work. Dr. Buergy reports consulting fees by NB Capital ApS / Nordic Biotech, honoraria by b.e. Imaging GmbH and participation on a Data Safety Monitoring Board or Advisory Board by PharmaMar S.A., outside the submitted work. Dr. Krug reports research funding by Merck KGaA, outside the submitted work. Dr. Saguner received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, BMS/Pfizer, and Medtronic; and speaker /advisory board fees from Abbott, Bayer Healthcare, Daiichi-Sankyo, Medtronic and Novartis, outside the submitted work. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Aims: Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K., Methods and Results: Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study. Besides routine clinical work-up, ajmaline challenge was performed after informed consent. A total of 23 subjects (11 female, mean age 27 ± 14 years) from 4 unrelated families with a family history of sudden cardiac death and familial diagnosis of the SCN5A-E1784K mutation underwent ajmaline challenge and genetic testing. Sixteen subjects (9 female) were found to be heterozygous carriers of SCN5A-E1784K. Ajmaline challenge was positive in 12 out of the 16 (75%) mutation carriers, but negative in all non-carriers. Following ajmaline, a significant shortening of the rate-corrected JT (JTc) interval was observed in mutation carriers. The baseline JTc interval was significantly longer in mutation carriers with a positive ajmaline challenge compared with those with a negative one., Conclusion: Overlap of LQT3 and BrS in patients carrying the most common mutation is high. Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Authors 2016. For permissions please email: journals.permissions@oup.com.)