Automatic identification of ablation targets in persistent atrial fibrillation: Initial experience with a new mapping tool.

INTRODUCTION: Strategies beyond pulmonary vein isolation (PVI) in persistent atrial fibrillation (persAF) are debated. A novel mapping tool provides algorithmic detection of ablation targets based on electrogram (EGM) properties specific to stable localized rotational activations. METHODS: The mapping tool was used on 31 patients (20 de novo). The algorithm was used to optimize PVI line placement and guide additional ablations. Targets were detected by calculating local cycle length (L-CL) and local spread of activation within that L-CL (Duty Cycle; DC) for EGMs with consistent morphology and activation. At least two left atrial (LA) maps (pre-PVI and post-PVI) were acquired in atrial fibrillation (AF) in all patients (except those with AF termination during PVI). Extra-pulmonary vein (PV) targets were compared between the two LA maps in each patient. Follow-up included Holter monitoring every 3 months. RESULTS: Patients had a median of 3 extra-PV drivers/targets. The majority (81%) were localized in the same areas between the two LA maps. All patients had progressive AF organization demonstrated by global activation slowing: histogram peak L-CL increased from 162 to 171 ms (post-PVI; p = .0003) than to 175 ms (posttarget ablation; p = .04). Moreover, L-CL dispersion was reduced by ablation; in 50% their values tended to cluster around two dominant cycles. In de novo patients AF terminated to sinus rhythm or atrial tachycardia (AT) within 48 h postprocedure in 88% of cases, and at 18 months mean follow-up recurrence occurred in only five (25%) patients (three persAF, two AT). There were no complications. CONCLUSION: The algorithmic detection of EGMs consistent with localized reentry during sequential mapping of persAF provided reproducible targets for ablation. This allowed personalized PVI and limited, highly-selective, extra-PV ablation. Results of this initial experience included progressive organization of AF with ablation and a low recurrence rate after a single procedure.

Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs.

In this work, we have developed a microfluidic cytotoxicity assay for a cell culture and detection platform, which enables both fluid handling and electrochemical/optical detection. The cytotoxic effect of anticancer drugs doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes, developed for targeted drug delivery, was evaluated using real-time impedance monitoring. The time-dependent effect of DOX on HeLa cells was monitored and found to have a delayed onset of cytotoxicity in microfluidics compared with static culture conditions based on data obtained in our previous study. The result of a fluorescent microscopic annexin V/propidium iodide assay, performed in microfluidics, confirmed the outcome of the real-time impedance assay. In addition, the response of HeLa cells to OX-induced cytotoxicity proved to be slower than toxicity induced by DOX. A difference in the time-dependent cytotoxic response of fibrosarcoma cells (HT1080) to free OX and OX-loaded liposomes was observed and attributed to incomplete degradation of the liposomes, which results in lower drug availability. The matrix metalloproteinase (MMP)-dependent release of OX from OX-loaded liposomes was also confirmed using laryngopharynx carcinoma cells (FaDu). The comparison and the observed differences between the cytotoxic effects under microfluidic and static conditions highlight the importance of comparative studies as basis for implementation of microfluidic cytotoxic assays.

Novel biomarkers of diabetic kidney disease: current status and potential clinical application.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Although both albuminuria and glomerular filtration rate (GFR) are well-established diagnostic/prognostic biomarkers of DKD, they have important limitations. There is, thus, increasing quest to find novel biomarkers to identify the disease in an early stage and to improve risk stratification. In this review, we will outline the major pitfalls of currently available markers, describe promising novel biomarkers, and discuss their potential clinical relevance. In particular, we will focus on the importance of recent advancements in multi-omic technologies in the discovery of new DKD biomarkers. In addition, we will provide an update on new emerging approaches to explore renal function and structure, using functional tests and imaging.

Treatment with eltrombopag of severe immune thrombocytopenia and hemolytic anemia associated with COVID-19 pneumonia: a case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Whether SARS-CoV-2 can trigger an autoimmune reaction against platelets and red blood cells remains unclear. Herein, we report a case of COVID-19 pneumonia associated with severe immune thrombocytopenia and hemolytic anemia. An 83-year-old woman was admitted to the hospital because of both dyspnea and diffuse mucocutaneous bleeding. Exams revealed hemolytic anemia (HA), severe immune thrombocytopenia (ITP), and bilateral pneumonia. Molecular testing confirmed a diagnosis of COVID-19 pneumonia. Thrombocytopenia did not respond to first-line treatment with immunoglobulin, corticosteroids, and platelet transfusions. Addition to therapy of the thrombopoietin receptor agonist, eltrombopag, resulted in full recovery. COVID-19 can be associated with ITP and HA. There are neither guidelines nor clinical experience on the treatment of COVID-19-associated ITP and our case, showing complete response to eltrombopag, may help clinicians in their practice during the COVID-19 pandemic. PLAIN LANGUAGE SUMMARY: The case of an 83-year-old woman with COVID-19 pneumonia associated with two severe blood diseases that cause platelet and red cell destruction Coronavirus disease 2019 (COVID-19) is caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We do not know exactly whether this virus can stimulate our immune system to react against platelets and red blood cells. Herein, we report a case of COVID-19 pneumonia associated with two severe blood diseases, immune thrombocytopenia, which causes platelet destruction, and hemolytic anemia, which causes red cell destruction. An 83-year-old woman was admitted to the hospital because of both difficulty in breathing and diffuse bleeding in mucosae and skin. Exams revealed hemolytic anemia, severe immune thrombocytopenia, and pneumonia in both lungs. Molecular testing confirmed a diagnosis of COVID-19 pneumonia. The first treatment with immunoglobulin, corticosteroids, and platelet transfusions was not enough to cure thrombocytopenia; the addition of eltrombopag which acts on the thrombopoietin receptor agonist resulted in full recovery. COVID-19 can be present together with immune thrombocytopenia and hemolytic anemia. As there are no guidelines on the treatment of immune thrombocytopenia in patients with COVID-19 and the clinical experience is limited, the complete response achieved with eltrombopag may help clinicians in their practice during the COVID-19 pandemic.