Takotsubo cardiomyopathy in a female patient with acute ureterolithiasis

Introduction: Takotsubo (stress cardiomyopathy/transient apical ballooning/broken heart syndrome) is disorder associated with transient left ventricular disfunction. It usually occurs in older women, 50% of them with neurologic or psychiatric conditions, or after emotional or physical stress, but also in absence of those triggers, and in younger population and men too. An excessive release of catecholamines seems to be pivotal role in the development of stress cardiomyopathy. Usually patients present with acute heart failure or acute coronary syndrome. Echocardiographically is almost undistinguishable from acute myocardial infarction due to left descending coronary artery occlusion.1,2 Case report: We herein present the case of 50-years-old female with nonregulated hypertension, dyslipidemia and obesity, presented with renal colic accompanied with nonspecific chest pain and dyspnea within 36 hours before admission. Initially she was presented to urologist due to dilation of channel system of the right kidney; radiographically possible stone in prevesical part of right ureter. Since her electrocardiogram showed subacute myocardial infarction with ST-segment elevation of anteroseptal region (Figure 1) with troponin T elevation up to 0.53 ug/L, she was admitted to Coronary Unit at the Department of Internal Medicine. Echocardiography showed closely suspicions on Takotsubo cardiomyopathy with preserved left ventricular systolic function (Figure 2), no valvular disease or intracavitary gradient. Her laboratory test results showed progression of deterioration of renal function and oliguria (urea 18,3 mmol/l, creatinine 264 mmol/l, eGFR EPI 17.4 mL/min), inflammation markers were high (Leucocytes 19 x 109, CRP 270 ug/L) predicting urosepsis and obstruction of the right kidney needed to be solved promptly. She was amicably transferred to tertiary center where urologists first resolved kidney obstruction since her kidney function was compromised, and after resolving urosepsis and full recovery she underwent coronarography that confirmed Takotsubo cardiomyopathy with no coronary artery obstruction lesions. Patient was managed with conservative therapy: ACE inhibitors, beta-blockers, analgesics and low molecular weight heparin. After six weeks she came for control echocardiography examination showing full recovery of apical ballooning and electrocardiographically complete resolution of earlier signs of anteroseptal infarction (Figure 3). Conclusion: Reversible left ventricular dysfunction (in this case we saw typical wall motion abnormality – apical ballooning with preserved global systolic function) seem to be pathognomonic in Takotsubo syndrome, and timelines of recovery is variable from patient to patient

Inflammation as a procoagulant state for thrombus manifestation in a patient with secondary dilated cardiomyopathy

Introduction: Inflammation is the dynamic process of defense made of chronological changes which are repercussions of the body on injury or infection, It is made of complex biological and biochemical reactions which includes crucial cells of the immune system and many lots of biological mediators stimulated with mechanical injuries, toxins, infections and reaction hypersensitivity. Because of the disorders of the homeostatic system it is bigger probability of appearing thromboembolic incidence especially in patients with some disorders. Dilated cardiomyopathy is disease with structural and functional changes of heart muscle.1-6 In the following case report the 43-year-old male with earlier known secondary dilated cardiomyopathy who presented with a pneumonia and thrombus in left and right ventricle. Case report: 44-year-old male patient with earlier known secondary dilated cardiomyopathy (post myocardial; from 2014) was hospitalized because of right pneumonia and heart failure. He was presented with dyspnea and chest pain and with elevated inflammation markers, D-dimer, and NT-proBNP). Because of chest pain we did the CT pulmonary angiography and we exclude pulmonary embolism. Echocardiography showed the dilatated (EDD 75 mm) left ventricle (LV) with reduced EF 25-28%. In akinetic apical part of the LV we noticed the thrombus (7x6 mm) (Figure 1). The right ventricle (RV) was dilatated (40 mm) with reduced contractility: TAPSE 13 mm, and RVEF around 30%. In the RV we noticed thrombus (32x22 mm) (Figure 2). With the TEE we confirm the formation of the thrombus (20x30 mm) in the apical part of the LV. With the antibiotic therapy (piperacillin with tazobactam and then with azithromycin and tetracycline and with the other medicaments) we achieve regression of pneumonia and resolution of symptoms of heart failure. In the further processing (in the tertial institution) with the cardiac magnetic resonance we prove that the formation in the left and the right heart was thrombus. The patient was prepared for heart transplantation. Conclusion: Every additional disease can complicate the earlier known heart disease especially with inflammation which has the procoagulant activity that encourages appearing thrombus. We must be more careful in the patient with some of the heart disease so that we do not predict it

Macros to Quantify Exosome Release and Autophagy at the Neuromuscular Junction of Drosophila Melanogaster

Automatic quantification of image parameters is a powerful and necessary tool to explore and analyze crucial cell biological processes. This article describes two ImageJ/Fiji automated macros to approach the analysis of synaptic autophagy and exosome release from 2D confocal images. Emerging studies point out that exosome biogenesis and autophagy share molecular and organelle components. Indeed, the crosstalk between these two processes may be relevant for brain physiology, neuronal development, and the onset/progression of neurodegenerative disorders. In this context, we describe here the macros “Autophagoquant” and “Exoquant” to assess the quantification of autophagosomes and exosomes at the neuronal presynapse of the Neuromuscular Junction (NMJ) in Drosophila melanogaster using confocal microscopy images. The Drosophila NMJ is a valuable model for the study of synapse biology, autophagy, and exosome release. By use of Autophagoquant and Exoquant, researchers can have an unbiased, standardized, and rapid tool to analyze autophagy and exosomal release in Drosophila NMJ.Code available at: https://github.com/IreneSaMi/Exoquant-AutophagoquantIdEx Bordeau

Arrhythmogenic right ventricular cardiomyopathy without arrhythmias?

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiovascular disease that predisposes to ventricular arrhythmias potentially leading to sudden cardiac death (SCD). In 1994 and 2010, an International Task Force document proposed guidelines for the standardized diagnosis of ARVC based on electrocardiographic (ECG), arrhythmic, morphological, histopathologic, and clinical-genetic factors.1-3 Our case report shows how important is to diagnose this disease, because the patients with ARVC should undergo lifelong clinical follow-up to periodically evaluate new onset or worsening of symptoms, progression of morphological and/or functional ventricular abnormalities, and ventricular arrhythmias in order to reassess the risk of SCD

A patient with permanent atrial fibrillation and very high bleeding risk – when is the optimal time to refer for left atrial appendage occluder device implantation?

Introduction: Most patients with atrial fibrillation (AF) should receive anticoagulant therapy to reduce the risk of systemic embolization. However, there are varying degrees of bleeding risk associated with anticoagulation thus reducing the number of candidates for this therapy. The left atrial appendage (LAA) is the usual source of clot embolisms. Percutaneous approaches, often referred to as LAA exclusion procedures, mechanically prevent embolization of LAA thrombi.1,2 We consider the placement of percutaneous LAA Occlusion Device (Amplatzer Amulet device) a good choice for patients with high bleeding risk

Uptake of the Necrotic Serpin in Drosophila melanogaster via the Lipophorin Receptor-1

The humoral response to fungal and Gram-positive infections is regulated by the serpin-family inhibitor, Necrotic. Following immune-challenge, a proteolytic cascade is activated which signals through the Toll receptor. Toll activation results in a range of antibiotic peptides being synthesised in the fat-body and exported to the haemolymph. As with mammalian serpins, Necrotic turnover in Drosophila is rapid. This serpin is synthesised in the fat-body, but its site of degradation has been unclear. By “freezing” endocytosis with a temperature sensitive Dynamin mutation, we demonstrate that Necrotic is removed from the haemolymph in two groups of giant cells: the garland and pericardial athrocytes. Necrotic uptake responds rapidly to infection, being visibly increased after 30 mins and peaking at 6–8 hours. Co-localisation of anti-Nec with anti-AP50, Rab5, and Rab7 antibodies establishes that the serpin is processed through multi-vesicular bodies and delivered to the lysosome, where it co-localises with the ubiquitin-binding protein, HRS. Nec does not co-localise with Rab11, indicating that the serpin is not re-exported from athrocytes. Instead, mutations which block late endosome/lysosome fusion (dor, hk, and car) cause accumulation of Necrotic-positive endosomes, even in the absence of infection. Knockdown of the 6 Drosophila orthologues of the mammalian LDL receptor family with dsRNA identifies LpR1 as an enhancer of the immune response. Uptake of Necrotic from the haemolymph is blocked by a chromosomal deletion of LpR1. In conclusion, we identify the cells and the receptor molecule responsible for the uptake and degradation of the Necrotic serpin in Drosophila melanogaster. The scavenging of serpin/proteinase complexes may be a critical step in the regulation of proteolytic cascades

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570