The Development of the Extravascular Defibrillator with Substernal Lead Placement: A New Frontier for Device-Based Treatment of Sudden Cardiac Arrest

Introduction: The extravascular ICD (EV ICD) system with substernal lead placement is a novel non-transvenous alternative to current commercially available ICD systems. The EV ICD provides defibrillation and pacing therapies without the potential long-term complications of endovascular lead placement. Methods: This paper summarizes the development of the EV ICD, including the pre-clinical and clinical evaluations that have contributed to system and procedural refinements to date. Results: Extensive pre-clinical research evaluations and 4 human clinical studies with >140 combined acute and chronic implants have enabled the development and refinement of the EV ICD system, currently in worldwide pivotal study. Conclusion: The EV ICD may represent a clinically valuable solution in protecting patients from sudden cardiac death while avoiding the long-term consequences of transvenous hardware. The EV ICD offers advantages over transvenous and subcutaneous systems by avoiding placement in the heart and vasculature; relative to subcutaneous systems, EV ICD requires less energy for defibrillation, enabling a smaller device, and provides pacing features such as anti-tachycardia and asystole pacing in a single system.

Single-Center Evaluation of Treatment Success Using Two Different Protocols for MRI–Guided Transurethral Ultrasound Ablation of Localized Prostate Cancer

ObjectivesTo assess differences in 24-month oncologic and functional outcomes in men with low to intermediate-risk prostate cancer treated with MRI-guided transurethral ultrasound ablation (TULSA) using intentionally conservative versus intensified treatment parameters.Patients and MethodsPatients from a single center involved in two multicenter trials were included in this analysis. This included 14 of 30 patients with Gleason 3 + 3 from a Phase I study using intentionally conservative treatment parameters, and 15 of 115 patients with Gleason ≤ 3 + 4 from a pivotal study using intensified parameters. Follow-up data compared across these cohorts included 12-month biopsy and MRI for all patients, and 24-month PSA, micturition and quality of life (IIEF, IPSS, IPSS-QOL). The prognostic value of baseline parameters and PSA kinetics on 12-month histological recurrence was evaluated by logistic regression.Results12-month biopsy revealed clinically significant residual disease in 4 (29%) and 2 (14%) patients from the Phase I and pivotal studies, respectively. PSA nadir was 0.7 ng/ml for Phase I and 0.5 ng/ml for pivotal study patients. Patient age at diagnosis, use of MRI fusion/systematic prostate biopsy, number of obtained cores at initial biopsy, PSA course, and PSA nadir were identified as prognostic factors for treatment success. All but one patient from each cohort maintained erection firmness sufficient for penetration. No cases of pad use were reported at 24 months. There were no Grade 4 or higher adverse events, and no late toxicity related to the procedure.ConclusionTwo-year follow-up demonstrated the efficacy of TULSA for the treatment of localized prostate cancer, and the durability of PSA and functional outcomes. Intensifying treatment parameters in the pivotal trial had no impact on safety or functional outcomes through 24 months, while reducing the recurrence rate for clinically significant disease. Careful patient selection by MRI fusion/systematic prostate biopsy and adequate follow-up through routine 12-month biopsy are recommended.

Alveolar Nitric Oxide as a Biomarker of COVID-19 Lung Sequelae: A Pivotal Study

Since SARS-CoV-2 emerged in 2019, strict monitoring of post-COVID-19 patients in order to ensure the early detection of sequelae and/or chronic organ damage that could been associated with the infection has been essential. Potential involvement of the NO pathway in the development of post-COVID-19 lung fibrotic alterations is feasible, since the majority of respiratory cells can produce NO, and fractional exhaled NO (FeNO) represents a biomarker of airway inflammation. The aim of this study was to investigate the potential utility of multiple-flow FeNO parameters in a post-COVID-19 population and to compare it with other indicators of lung damage proposed in the literature. We enrolled 20 patients hospitalized for COVID-19, who underwent clinical, respiratory functional (including PFTs and FeNO) and radiological follow-up after discharge. Compared with age- and sex-matched healthy controls, post-COVID-19 patients showed significantly higher FeNO 350 mL/s and CaNO levels. Moreover, among the parameters included in the follow-up, CaNO showed the best accuracy in indicating predominant fibrotic changes and GGO at CT scan. To our knowledge, this preliminary study has investigated for the first time multiple-flow FeNO parameters in a post-COVID-19 population. The evidence of increased CaNO values may imply the persistence of alveolar and bronchiolar inflammation and/or a mild impairment of the alveolar-capillary membrane in these patients.

Safety and Tolerability of the BNT162b2 mRNA COVID-19 Vaccine in Dialyzed Patients. COViNEPH Project

Background and Objectives: The Pfizer-BioNTech (BNT162b2) COVID-19 mRNA vaccine has demonstrated excellent efficacy and safety in phase 3 trials. However, no dialyzed patients were included, and therefore safety data for this patient group is lacking. The aim of the study was to assess the safety and tolerances of vaccinations with BNT162b2 performed in chronically dialyzed patients. Materials and Methods: We performed a prospective cohort study including a group of 190 dialyzed patients (65% male) at median age 68.0 (55–74) years. 169 (89.0%) patients were treated with hemodialysis and 21 (11.0%) with peritoneal dialysis. The control group consisted of 160 people (61% male) without chronic kidney disease at median age 63 (range 53–77) years. Both groups were vaccinated with BNT162b2 with a 21-day interval between the first and the second dose. Solicited local and systemic reactogenicity, unsolicited adverse events and antipyretic and pain medication use were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA Center for Biologics Evaluation and Research guidelines. Results: 59.8% (dose 1), 61.4% (dose 2) and 15.9% (dose 1), 29.4% (dose 2) dialyzed patients reported at least one local and one systemic reaction respectively within seven days after the vaccination. Many local and systemic solicited reactions were observed less frequently in dialyzed patients than in the age and sex matched control group and much less frequently than reported in the pivotal study. They were mostly mild to moderate, short-lived, and more frequently reported in younger individuals and women. No related unsolicited adverse events were observed. Conclusions: We have shown here that BNT162b2, an mRNA vaccine from Pfizer-BioNTech against SARS-COV-2 is safe and well-tolerated by dialyzed patients. The results can be useful for the nephrological community to resolve patients’ doubts and reduce their vaccine hesitancy.