Search

BACKGROUND: Glioblastoma (GBM) is a highly lethal disease despite integrated treatment comprising radiotherapy plus concomitant and adjuvant temozolomide, with a median overall survival of less than 15 months. For recurrent glioblastoma, there is yet no standard therapy, considering that Bevacizumab have failed to improve overall survival (OS) while regorafenib had a little benefit over standard chemotherapy. In addition, the disease control rate is almost exclusively stability, with a poor objective response rate. CASE REPORT: Here we present a case of rapid response to regorafenib in early glioblastoma progression at the end of adjuvant radiotherapy: after a single cycle of regorafenib the patient observed an impressive improvement in clinical condition, disappearance of headaches and a clear reduction of neoplastic tissue in MRI. A brief review about new radiological patterns in Magnetic Resonance Imaging (MRI) related to the introduction in clinical practice of antiangiogenic drugs and tyrosine kinase inhibitors has also been carried out. CONCLUSIONS: Regorafenib was certainly a first turning point in the second-line treatment of GBM, showing longer response rates and mostly disease stability than bevacizumab. A switch-maintenance strategy with tyrosine kinase inhibitors may represent a valid second-line therapeutic option. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to determine the optimal target heart rate (HR) for the use of exercise-induced T-wave alternans (TWA) as an index for risk of malignant ventricular tachyarrhythmias.Background: Rate-dependent TWA is an index of vulnerability to ventricular tachyarrhythmias. However, false positive TWA was reported to occur in normal subjects at high HR.Methods: Two groups were evaluated: Group I: 50 patients with malignant ventricular tachyarrhythmias, who received an implantable cardioverter-defibrillator (ICD); and Group II: 55 age-matched normal subjects. In both Groups, TWA was evaluated during symptom-limited bicycle exercise test.Results: Peak HR during exercise test was 103 +/- 17 beats/min in Group I, versus 124 +/- 18 beats/min in Group II (P < 0.001). In Group I, 4 patients were excluded from analysis, due to high noise level or frequent ectopy during exercise. Out of the remaining 46 patients, TWA was present in 28 patients (61%), and absent in 18 (39%). In group II, TWA was present in four subjects (7%), and absent in 51 (93%). HR at the onset of TWA was 91 +/- 11/min in Group I, and 119 +/- 12/min in Group II (P < 0.001). Receiver operated characteristics curves demonstrated that a HR of 115 beats/min was the cutoff with the best sensitivity and specificity for TWA (100 and 96%, respectively). None of the patients in Group I developed TWA at HR > 115 beats/min, while two out of four in Group II had TWA at HR > 115/minutes. However, 13 patients in Group I who had no TWA were unable to exercise to a peak HR > 115 beats/min, compared to nine subjects in Group II.Conclusions: A target HR of 115 beats/min was highly sensitive and specific for determination of exercise-induced TWA as an index of risk of malignant ventricular tachyarrhythmias. However, a significant number of patients may not be able to achieve this target HR, resulting in an indeterminate test. The value of pharmacologic testing in this group should be assessed. [ABSTRACT FROM AUTHOR]

The LQTS is a prime example of how molecular biology, ion channel, cellular, and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and acquired LQTS are due to abnormalities (intrinsic and/or acquired) of the ionic currents underlying cardiac repolarization. In this review, the continually unraveling molecular biology of congenital LQTS is discussed. The various pharmacological agents associated with the acquired LQTS are listed. Although it is difficult to predict which patients are at risk for TdP, careful assessment of the risk-benefit ratio is important before prescribing drugs known to be able to cause QT prolongation. The in vivo electrophysiological mechanism of TdP in the LQTS is described using, as a paradigm, the anthopleurin-A canine model, a surrogate for LQT3. In the LQTS, prolonged repolarization is associated with increased spatial dispersion of repolarization. Prolongation of repolarization also acts as a primary step for the generation of EADs. The focal EAD induced triggered beat(s) can infringe on the underlying substrate of inhomogeneous repolarization to initiate polymorphic reentrant VT, sometimes having the characteristic twisting QRS configuration known as TdP. The review concludes by discussion of the clinical manifestations and current management of both the congenital and acquired LQTS. The initial therapy of choice for the large majority of patients with the congenital LQTS is a beta-blocking drug. This therapy seems to be effective in LQT1 and LQT2 patients, but may not be as effective in LQT3 patients. Other therapeutic options include pacemakers, cervicothoracic sympathectomy, and the implantable cardioverter defibrillator. Recent molecular genetic studies have suggested several genotype specific therapies; however, long-term efficacy data are not available. [ABSTRACT FROM AUTHOR]

The incidence and time course of complex ventricular arrhythmias and of the abnormal signal averaged electrocardiogram were studied prospectively in 90 patients in the first two months after acute myocardial infarction. Serial recordings of both 24 hour ambulatory and signal averaged electrocardiograms were obtained 0-5 days (phase 1), 6-30 days (phase 2), and 31-60 days (phase 3) after infarction. A total of 264 ambulatory electrocardiograms and 264 signal averaged electrocardiograms were available for analysis. Complex ventricular arrhythmias were seen in 31%, 17%, and 38% of patients during phases 1, 2, and 3 respectively, and abnormal signal averaged electrocardiogram in 13%, 24%, and 16%. The incidence of complex ventricular arrhythmias was not significantly different in patients with or without an abnormal signal averaged electrocardiogram in the entire study period nor in any of the three phases after infarction. During phase 2 when abnormal signal averaged electrocardiograms were most common complex ventricular arrhythmias were least common. This lack of correlation suggests that the abnormal signal averaged electrocardiogram and complex ventricular arrhythmias after infarction have different electrophysiological bases. [ABSTRACT FROM PUBLISHER]

The role of supraventricular extrasystoles in the initiation of ventricular arrhythmia was studied in 72 consecutive patients who developed primary ventricular fibrillation during the acute phase of myocardial infarction. In six patients (8%), a total of 12 episodes of ventricular fibrillation and 16 episodes of ventricular tachycardia were initiated by supraventricular extrasystoles. Ventricular fibrillation and tachycardia were initiated by single supraventricular extrasystoles in 16 and by salvos greater than or equal to two beats in 12 episodes. The RR coupling interval of the supraventricular impulse immediately preceding ventricular tachycardia ranged from 240 to 420 ms (mean 356 (62)) and was characteristic of R-on-T (prematurity index less than 1) in 63% of episodes. Average peak serum creatine kinase activity in the six patients in whom ventricular tachycardia was initiated by a supraventricular extrasystole was 1275 units compared with 720 units in the remaining 66 patients. Five of these six patients later showed evidence of pump failure. Lignocaine or procainamide or both suppressed the ventricular arrhythmia in five of the six patients. The initiation of ventricular fibrillation or tachycardia by supraventricular extrasystoles in acute myocardial infarction is not uncommon and may reflect the increased vulnerability of the heart after a large infarct. These arrhythmias may respond to drugs that suppress ventricular irritability. [ABSTRACT FROM PUBLISHER]

We report 2 cases of exudative left pleural effusion following radiofrequency catheter ablation of cardiac arrhythmias complicated by cardiac perforation. We suggest that radiofrequency ablation may be a previously unsuspected cause of postcardiac injury syndrome. [ABSTRACT FROM AUTHOR]

Background: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy., Methods: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data., Results: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%., Conclusions: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Valentina Tuninetti: honoraria from MSD Oncology, GSK and EISAI, Elisa Virano: None declared, Vanda Salutari: Honoraria: AstraZeneca, MSD Oncology, GSK, PhamaMar, Novocure, Consulting: AstraZeneca, Novocure, Travel, Accomodations, Expenses: GSK, PharmaMar, Andrea Ricotti: None declared, Carmela Pisano: Advisory board: AstraZeneca, MSD Oncology, GSK, Monica Ducceschi: None declared, Giacinto Turitto: None declared, Giuseppa Scandurra: None declared, Maria Cristina Petrella: Honoraria from Astrazeneca, MSD, GSK, Valeria Forestieri: None declared, Monica Rizzetto: None declared, Serafina Mammoliti: None declared, Grazia Artioli: honoraria from AstraZeneca, MSD Oncology, GSK, Raffaella Cioffi: None declared, Lucia Borsotti: None declared, Marco Bellero: None declared, Chiara Rognone: None declared, Vittoria Carbone: None declared, Gabriella Ferrandina: None declared, Mara Mantiero: None declared, Carmen Azzolina: None declared, Eleonora Geninatti: None declared, Sandro Pignata: Research Funding: AstraZeneca, MSD Oncology, Roche, GSK, Pfizer, Honoraria: AstraZeneca, MSD Oncology, Roche, GSK, Novartis, EISAI, PharmaMar, Giorgio Valabrega: Consulting fees from GSK; honoraria from AstraZeneca, GSK, and MSD; travel support from AstraZeneca and PharmaMar; participation in advisory boards for AstraZeneca, EISAI, GSK, and MSD., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Non-Small Cell Lung Cancer (NSCLC) with bone metastasis and poor performance status has the worst prognosis even in strong PD-L1 expression patients. Treatment approach includes immuno- or chemo-immunotherapy, Radiotherapy (RT) and Bone-Targeted Therapy (BTT) but there is insufficient data to suggest the best time to use each of them, alone or in combination. Using an integrated and synergistic treatment strategy with immunotherapy, radiotherapy, and Denosumab as BTT is probably the best treatment planning for metastatic NSCLC for both good and poor performance status patients, although more data are needed to confirm this approach. Here we describe an interesting case report on patient with extensive bone involvement from NSCLC and PS >2 treated simultaneously with radiotherapy, immunotherapy and BTT, achieving an excellent clinical benefit, radiological and metabolic complete response, as a sort of Lazarus effect. We analyzed our result comparing with currently published data about radio-immunotherapy or immunotherapy and BTT combination even though there is no published experience about integration of all 3 treatments. Approval studies often do not represent real-world experience (RWE), so we analyzed data from both RWE and clinical trials., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes., Methods: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately., Results: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001)., Conclusion: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Funding Support and Author Disclosures Dr Parikh serves on the advisory boards of Abbott Vascular, Boston Scientific, and Medtronic. Dr Kobayashi serves as a consultant to Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Glioblastoma multiforme (GBM) is a fatal brain tumor without effective drug treatment. In this study, we highlight, for the first time, the contribution of chromatin remodeling gene Lysine (K)-specific demethylase 5C ( KDM5C ) in GBM via an extensive analysis of clinical, expression, and functional data, integrated with publicly available omic datasets. The expression analysis on GBM samples (N = 37) revealed two informative subtypes, namely KDM5C High and KDM5C Low , displaying higher/lower KDM5C levels compared to the controls. The former subtype displays a strong downregulation of brain-derived neurotrophic factor ( BDNF )-a negative KDM5C target-and a robust overexpression of hypoxia-inducible transcription factor-1A ( HIF1A ) gene, a KDM5C modulator. Additionally, a significant co-expression among the prognostic markers HIF1A , Survivin , and p75 was observed. These results, corroborated by KDM5C overexpression and hypoxia-related functional assays in T98G cells, suggest a role for the HIF1A-KDM5C axis in the hypoxic response in this tumor. Interestingly, fluorescence-guided surgery on GBM sections further revealed higher KDM5C and HIF1A levels in the tumor rim niche compared to the adjacent tumor margin, indicating a regionally restricted hyperactivity of this regulatory axis. Analyzing the TCGA expression and methylation data, we found methylation changes between the subtypes in the genes, accounting for the hypoxia response, stem cell differentiation, and inflammation. High NANOG and IL6 levels highlight a distinctive stem cell-like and proinflammatory signature in the KDM5C High subgroup and GBM niches. Taken together, our results indicate HIF1A-KDM5C as a new, relevant cancer axis in GBM, opening a new, interesting field of investigation based on KDM5C as a potential therapeutic target of the hypoxic microenvironment in GBM.

The coronavirus disease 2019 crisis is a global pandemic of a novel infectious disease with far-ranging public health implications. With regard to cardiac electrophysiology (EP) services, we discuss the "real-world" challenges and solutions that have been essential for efficient and successful (1) ramping down of standard clinical practice patterns and (2) pivoting of workflow processes to meet the demands of this pandemic. The aims of these recommendations are to outline: (1) essential practical steps to approaching procedures, as well as outpatient and inpatient care of EP patients, with relevant examples, (2) successful strategies to minimize exposure risk to patients and clinical staff while also balancing resource utilization, (3) challenges related to redeployment and restructuring of clinical and support staff, and (4) considerations regarding continued collaboration with clinical and administrative colleagues to implement these changes. While process changes will vary across practices and hospital systems, we believe that these experiences from 4 different EP sections in a large New York City hospital network currently based in the global epicenter of the coronavirus disease 2019 pandemic will prove useful for other EP practices adapting their own practices in preparation for local surges.

Congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. Although congenital LQTS remains the domain of cardiologists, cardiac electrophysiologists and specialised centres, the much more frequently acquired LQTS is the domain of physicians and other members of healthcare teams required to make therapeutic decisions. This paper reviews the electrophysiological mechanisms of acquired LQTS, its ECG characteristics, clinical presentation, and management. The paper concludes with a comprehensive review of the electrophysiological mechanisms of torsade de pointes., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.