bluuebunny/crossref_metadata_2025 huggingface dataset:
544 Two cases of constrictive pericarditis temporally associated with mRNA-1273 COVID-19 vaccination
Authors: Diana Davide , Cardillo Ilaria , Polizzi Vincenzo , Musumeci Francesco
Published: December 2021

Aims

The SARS-CoV-2 pandemic has led to the development of the mRNA vaccines in humans which are well tolerated, safe, and highly efficacious; however, post-marketing surveillance is revealing potential rare cardiac adverse effects as acute pericarditis. We herein report two cases of symptomatic constrictive pericarditis following administration of the second dose of mRNA-1273 (Moderna) SARS-CoV-2 vaccine.

Methods and results

Case summary: A 75 years old male with history of hypertension and COPD presented to our Hospital approximately one month after the second dose of mRNA-1273 SARS-CoV-2 Vaccine with dyspnoea and leg oedema. Routine analysis resulted normal, no increasing of inflammatory markers or ECG abnormalities. Echocardiogram showed circumferential fibrinous pericardial effusion without tamponade and typical features of constrictive pericarditis: annulus reversus, ventricular interdependence, expiratory diastolic flow reversal in hepatic vein, inferior vena cava plethora. Pleural ultrasound showed bilateral pleural effusion that was sampled and showed a transudate fluid. Tumoral marker and a CT Scan, autoimmunity panel, blood tests for bacteraemia and Quantiferon were negative. Cardiac magnetic resonance imaging confirmed thickening of pericardium. A 68 years old male with history of ischaemic heart disease with previous CABG, hypertension, dyslipidaemia and chronic kidney disease presented with palpitations and mild legs swelling. Approximately, 2 months before he received the second dose of mRNA-1273 SARS-CoV-2 vaccine. Routine blood examinations resulted normal, ECG showed a right bundle branch block. Echocardiogram showed a mild enlargement of LV with normal systolic function, a moderate primary mitral regurgitation and a circumferential pericardial effusion, showing signs of constrictive syndrome. CT Scan demonstrated pericardium thickness. Constrictive pericarditis may represent a subacute complication of an asymptomatic exudative acute pericarditis. Although cases of acute pericarditis have been reported after SARS-CoV-2 vaccine, to our knowledge, the association with constrictive pericarditis has not been described. The temporal link between vaccination and symptoms development as the biological plausibility of autoimmune or cross-reaction response to vaccination in predisposed subjects could suggest a possible correlation as an adverse event, even if causality could not be established.

Conclusions

We present two cases of constrictive pericarditis occurring after mRNA-1273 SARS-CoV-2 vaccination, aiming further data to confirm a causal role.
172 Two mutations, one patient: which phenotype?
Authors: Giovannetti Alessandro , Accietto Antonella , Caponetti Angelo Giuseppe , Saturi Giulia , Ponziani Alberto , Massa Paolo , Sguazzotti Maurizio , Longhi Simone , Galiè Nazzareno , Gagliardi Christian
Published: December 2021

Methods and results

Woman, 55 years old, she has as comorbidity high blood pressure and mild obesity. She came at our attention to perform screening cardiological exams after her brother, who was affected by amyloidotic TTR-related cardiomyopathy with Val30Met mutation, died for sudden cardiac death. At the first evaluation the patient is completely asymptomatic, she has not angor, dyspnoea and heartbeat. The ECG and echocardiography were negative for amyloidotic signs of heart involvement. The Tc-99-DPD scintigraphy showed no cardiac uptake (visual score = 0). To complete the diagnostic path the patient had been evaluated by a neurologist with electromyography, which was negative, and genetic test, which confirmed the presence of Val30Met mutation of TTR-gene. For this last outcome we decided to follow the patient at our clinics. In the following years the patient developed a progressive reduction of exercise tolerance and symmetric negative T waves in anterolateral and inferior lead at ECG. The echocardiogram showed a progressive medio-apical septal hypertrophy. To exclude an ischaemic cause the patient made a stress myocardial scintigraphy, which was negative for ischaemic signs, and she underwent to cardiac MRI which showed a septal thickness of 16 mm without amyloidotic radiological signs in T1-weighted and LGE sequences. For this reason, we suspected that the patient had a hypertrophic cardiomyopathy and she had been undergone another time to genetic test which confirmed the Val30Met TTR-mutation and MYBPC3 mutation. Usually, this last gene mutation for myosin binding protein C is associated with late-onset hypertrophic cardiomyopathy. Into account the new diagnosis and her sudden cardiac death family history we calculated the patient’s HCM-risk score which was under 4%, so that we did not undergo the patient to ICD implantation.

Conclusions

The case report is a rare example of coexistence of the transthyretin gene mutation and myosin binding protein C in the same patient. In this case to perform a correct diagnosis, it is crucial use an integrated multimodal approach including ECG, echocardiography and cardiac MRI.
358 Clinical characteristic and natural history of chemotherapy induced dilated cardiomyopathy
Authors: Lalario Andrea , Del Mestre Eva , Lo Casto Michele , Nuzzi Vincenzo , Cannatà Antonio
Published: December 2021

Chemotherapy can lead to chemotherapy-induced dilated cardiomyopathy (CI-DCM), recognized as one of the Non-ischaemic Dilated Cardiomyopathy (DCM) phenotypes characterized by worse outcome. Evidences on a direct comparison between idiopathic-DCM (iDCM) and CI-DCM still lack. We included all the consecutive patients enrolled in the Trieste Muscle Heart Disease Registry. C-DCM was defined according to current recommendations. Uni- and multivariable analysis and Kaplan-Meier were performed. The primary outcome was all-cause death and the secondary outcomes were cardiac death and a composite of heart failure hospitalization, heart transplantation, ventricular assist-device implantation and major ventricular arrhythmias. The study included 511 patients (499 patients affected by iDCM and 52 patients affected by CI-DCM). Compared to iDCM, CI-DCM patients were older (51 ± 14 years vs. 58 ± 3 years respectively, P < 0.001) and had a higher LVEF (35%±10 vs. 32%±9, P = 0.03). CI-DCM patients had a higher incidence of all-cause of death compared to iDCM (36.5% vs. 8.4%, P < 0.001), while the incidence of cardiac death (7% in the CI-DCM group vs. 4% in the iDCM group, P = 0. 232) and of the composite secondary outcome was comparable amongst the two groups. At multivariable analysis, the diagnosis of CI-DCM was an independent predictor of primary outcome incidence (HR: 5.79, 95% CI: 1.83–18.27), P = 0.003, together atrial fibrillation. In a well-selected DCM cohort, patients with a chemotherapic etiology had a higher incidence of all-cause mortality compared to iDCM, while the incidence of cardiac adverse events was comparable among CI-DCM and iDCM.
334 Hereditary transthyretin amyloidosis: main features and profiles of different clinical phenotypes
Authors: Massa Paolo , Caponetti Angelo Giuseppe , Saturi Giulia , Ponziani Albero , Sguazzotti Maurizio , Accietto Antonella , Dal Passo Beatrice , Longhi Simone , Bonfiglioli Rachele , Mattana Francesco , Guaraldi Pietro , Cortelli Pietro , Galié Nazzareno , Biagini Elena , Gagliardi Christian
Published: December 2021

Aims

Hereditary transthyretin-related amyloidosis (h-ATTR) is a systemic infiltrative disease caused by a single amino acid mutation on the transthyretin (TTR) gene, which destabilizes the protein and can determine its deposition on multiple organs, including heart and peripheral nervous system. We aimed to characterize and compare clinical, instrumental, and prognostic features of patients affected by h-ATTR by dividing the population into the disease’s main phenotypes (unaffected carriers, cardiac, neurological or mixed phenotype).

Methods and results

Two hundred and eighty-five subjects of a single-centre cohort with a recognized pathogenic mutation on TTR gene were retrospectively included in the analysis. Phenotypes of disease were defined at baseline. Neurological phenotype (NP) was defined according to sensorimotor and/or autonomic dysfunction, while cardiac phenotype (CP) was defined in the presence of unexplained maximum wall thickness >12 mm and other typical echocardiographic findings. Unaffected carriers (UC) and mixed phenotypes (MP) presented none or both of the above-mentioned features, respectively. Two hundred and ten patients showed clinical signs of the disease, 37 (13%) with CP, 65 (23%) with NP and 108 (38%) with MP, while 75 subjects (26%) were UC. Ile68Leu was the most represented mutation (96 subjects, 34%), followed by Val30Met (21%) and Glu89Gln (13%). NP patients (mostly Val30Met) had mPND score >1 in 45% of patients, were younger at diagnosis (mean 47 years, P < 0.001 vs. CP/MP), and sex was equally distributed. In contrast, CP patients were older at diagnosis (mean 70 years, P < 0.001 vs. CP/MP), predominantly male (as well as in MP) with a higher incidence of tunnel carpal syndrome and a shorter time interval between onset of symptoms and diagnosis (mean 17 months, P < 0.001 vs. CP/MP). NYHA class, ECG findings, left ventricular wall thickness, and ejection fraction did not significantly differ between CP and MP. After a mean follow-up of 59 months, 98 (34%) patients died. On a Kaplan–Meier survival analysis, mean survival times were 208, 123, 150, and 95 months for UC, CP, NP, and MP, respectively, with a statistically significant difference in affected patients between NP and MP (P = 0.012).

Conclusions

H-ATTR is a rare systemic disorder whose natural history, including age of onset, clinical characteristics, and instrumental findings, is strongly influenced by primary phenotypes, ranging from the excellent prognosis of unaffected carriers to the inauspicious outcome of mixed phenotypes.
577 Bisoprolol for the treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy
Authors: Monda Emanuele , Lioncino Michele , Palmiero Giuseppe , Rubino Marta , Cirillo Annapaola , Verrillo Federica , Fusco Adelaide , Caiazza Martina , Mazzella Marialuisa , Moscarella Elisabetta , Dongiglio Francesca , Sepe Joseph , Russo Maria Giovanna , Pacileo Giuseppe , Limongelli Giuseppe
Published: December 2021

Aims

To evaluate to role of bisoprolol to control symptoms and left ventricular outflow tract obstruction (LVOTO) in a consecutive cohort of adults with hypertrophic cardiomyopathy (HCM).

Methods and results

In this retrospective study, patients with HCM with an LVOT gradient ≥50mmHg after Valsalva manoeuvre and New York Heart Association (NYHA) class II-III symptoms were assigned to receive bisoprolol (starting at 1.25 mg daily). The initial dose was increased every two weeks to achieve the target in LVOT gradient <30 mmHg or the maximum tolerated dose. The primary endpoint was the achievement of a LVOT gradient <30 mmHg and ≥1 NYHA class improvement. The secondary endpoints were proportion of patients with LVOT gradient <30 mmHg or < 50 mmHg, proportion of patients with ≥1 NYHA class improvement, and change from baseline in LVOT gradient. Between December 2001 and December 2020, 92 patients were enrolled into the study. Sixteen (17%) patients on bisoprolol met the primary endpoint. Bisoprolol reduced the LVOT gradient to less than 30 mmHg in 33 (36%) patients, to less than 50 mmHg in 57 (62%), and improved NYHA class in 30 (33%). The mean reduction of LVOT gradient on bisoprolol was 28 (±14) mmHg and the percentage reduction was 42 (±21)%. In 35 (39%) patients, bisoprolol did not reduce the gradient to less than 50 mmHg requiring disopyramide and/or myectomy to achieve this goal.

Conclusions

Treatment with bisoprolol was well-tolerated and effective in relieving obstruction and improving symptoms in a significant proportion of patients with symptomatic obstructive HCM.
639 A case of acute transient constrictive pericarditis—an unusual presentation
Authors: Spissu Paolo Marco Pietro , Angius Simone , Marchetti Maria Francesca , Caggiari Ludovica , Gioi Alessandra , Mura Giulia , Mandas Martina , Licciardi Marco , Meloni Luigi , Montisci Roberta
Published: December 2021

Aims

Transient constrictive pericarditis (TCP) is a rare manifestation which can occur in up to 15% of cases of acute pericarditis and most have resolution after 3 months of anti-inflammatory therapy.

Methods and results

We present the case of a young guy who showed up at our emergency department complaining of pericarditic chest pain and fever up to 39 °C degrees since the previous 4 days. After physical examination, electrocardiogram, blood tests, chest X-ray, and echocardiography acute pericarditis with severe pericardial effusion (more than 20 mm of thickness) were diagnosed and an empiric anti-inflammatory therapy with ibuprofen and colchicine was started. After 2 weeks of therapy, patient was not clinically improving with a worsened pericardial effusion and only a mild reduction of inflammatory markers. During an echocardiographic examination, features of constrictive physiology were discovered: respirophasic interventricular septal shift, increased respiratory variation of the mitral and tricuspidal inflow, plethoric inferior vena cava, and ‘annulus reversus’ and ‘annulus paradoxus’ on Tissue Doppler Imaging (TDI). Cardiac magnetic resonance (CMR) was also performed to confirm the diagnosis of acute pericardial constriction: it revealed increased T2-weighted imaging signal and increased Delayed Gadolinium Enhanced (DGE) signal, respectively consistent with oedema and with neovascularization, both suggestive of acute pericardial inflammation. Therefore, oral low doses corticosteroid was started After 2 weeks course of ‘triple therapy’ the patient was clinically improved and the echocardiographic features of constrictive physiology were no longer present thus allowing his discharge and the continuation of therapy at home.

Conclusions

This case was remarkable because it showed that constrictive pericarditis may present in a reversible form with medical therapy, this meaning it is due to pericardial oedema, inflammation and fibrin deposition similar to acute pericarditis rather than the pericardial fibrosis and calcification more commonly seen in chronic pericardial constriction.
566 Transthyretin and light-chain cardiac amyloidosis: clinical characteristics, echocardiographic findings, and outcomes of a large cohort of patients in Northern Italy
Authors: De Angelis Maria Grazia , Tomasoni Daniela , Pancaldi Edoardo , Pezzola Elisa , Saccani Nicola , Nardi Matilde , Cani Dario Salvatore , Lombardi Carlo Mario , Metra Marco
Published: December 2021

Aims

To describe the characteristics of a cohort of patients with cardiac amyloidosis (CA) and to compare the two most common phenotypes of CA, transthyretin (ATTR) and immunoglobulin light-chain (AL).

Methods and results

One-hundred and eighty patients [n = 115 (64%) men, 74 ± 11 years] were retrospectively included from January 2013 to April 2021 in a single centre in Northern Italy. The majority [n = 102 (57%)] had ATTR-CA, whereas 78 patients (43%) had AL-CA. ATTR-CA patients were older (79 ± 7 vs. 66 ± 10 years, P < 0.001) and with higher prevalence of cardiovascular comorbidities, compared to those with AL-CA. ATTR-CA patients had higher N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and troponin levels, and lower haemoglobin and estimated glomerular filtration rate. Echocardiographic findings suggested a more advanced stage of the disease in the ATTR-CA subgroup [left ventricular ejection fraction (LVEF), 51 ± 10% vs. 60 ± 9%; global longitudinal strain (GLS), −11 ± 3% vs. −13 ± 4%; peak systolic wall motion velocity, 4.9 ± 1.7 vs. 6.4 ± 1.9; left ventricular mass index (LVMI) 316 ± 133 g/m2 vs. 157 ± 72 g/m2; left atrium volume index (LAVI) 48 ± 17 ml vs. 40 ± 16 ml; right ventricular diameter 31 ± 9 mm vs. 22 ± 5 mm; tricuspidal annular plane systolic excursion (TAPSE) 17 ± 5 vs. 19 ± 5; all P < 0.05). During a median follow-up of 15 (6–31) months, 68 (38%) patients died. All-cause death occurred in 31% vs. 46% patients with ATTR- and AL-CA, respectively. AL-CA was an independent predictor of mortality (adjusted hazard ratio 2.62, 95% confidence interval 1.55–4.43; P < 0.001). Other independent predictors of mortality were age, systolic blood pressure, Nt-proBNP, troponin and GLS. When cardiovascular (CV) death was considered, there was no significant difference between the two phenotypes (log rank P = 0.384).

Conclusions

Despite ATTR-CA patients showed worse baseline characteristics, suggesting a more advanced disease at presentation, AL-CA phenotype was associated with a higher risk of all-cause death. Of note, CV mortality was comparable between the two groups.
285 A rare case of atypical, non-triggered takotsubo recurrence
Authors: Widmann Maddalena , Lia Micaela , Rizzetto Francesca , Tavella Domenico , Prati Daniele , Ribichini Flavio Luciano
Published: December 2021

Aims

Takotsubo syndrome (TTS) is an acute and reversible heart failure syndrome that, at presentation, mimics acute myocardial infarction. The most common echocardiographic manifestation is the so-called ‘apical ballooning’, but other much less common wall motion patterns have been described. The pathophysiology of the syndrome is not fully understood, but there is considerable evidence that sympathetic stimulation plays a central role. The prevalence of this syndrome is higher in post-menopausal women and in most cases, but not invariably, precipitated by an emotional or physical triggering event. A close relation between brain and circulatory system has been observed and for this reason psychiatric and neurologic disorders are often recognized as precipitating conditions. Although many risk factor persist after the acute manifestation, Takotsubo recurrences do represent an exception, especially in the absence of a clear precipitating event.

Methods and results

A 70-year-old woman was admitted for anginal pain associated with ischaemic electrocardiographic alterations and elevation of cardiac biomarkers. The coronary angiography with left ventriculogram and the echocardiographic findings were consistent with a diagnosis of mid-ventricular Takotsubo. Cardiac magnetic resonance confirmed the absence of an ischaemic pattern or evidence of infectious myocarditis. This case represents a recurrence of TTS, in fact two years earlier the patient was hospitalized to our division for stress cardiomyopathy with typical apical ballooning. Also in the present occasion, she had a favorable clinical course, with a complete recovery of the cardiac function at subsequent evaluations. The unicity of this case lies above all in the absence of a clear trigger event. Although, an altered mental status was present because the patient suffered from anxiety and depression on pharmacological treatment, with periods of exacerbation but not in occasion of the recurrence.

Conclusions

TTS is not a benign condition, with recurrence being possible even in the absence of precipitating events. Based on registry data, annual rate of Takotsubo recurrence is 1.5–1.8% and is estimated to reach 4% in life. A variable TTS pattern at recurrence is common in up to 20% of cases. Our paper reports a unique case of recurrent Takotsubo syndrome with variable patterns of ventricular involvement, with neither physical nor psychological trigger. Nevertheless, for what concerns our case, the psychiatric condition the patient suffered from, could have played a role of permanent status of sympathetic activation, that in the end elicitates the occurrence of the syndrome. A better understanding of the pathophysiology of the syndrome is needed to find evidence-based therapeutic strategies that could prevent recurrence.
34 The diagnostic and therapeutic pathway of the patient with SCA: Nursing&Tech assistance
Authors: Santucci Stefano , Franchetti Domenico , Emanuelli David , Cerulli Martina , Marcotuttli Sara , Santucci Matteo , Gasperini Vittorio
Published: December 2021

Cardiomyopathies to be the first cause of death. The patient who suffers from acute heart disease, after clinical evaluation, is subjected to a diagnostic–therapeutic process that involves several professional figures which include the doctor and the ambulance nurse, the doctor and all the emergency room staff who accept the patient and, if the clinical indication is oriented towards a vascular occlusion disease, the doctor and the technical-nursing team of the haemodynamics service activated in urgency. To diagnose with certainty the presence of vascular disease we make use of diagnostic systems that use ionizing radiation; the haemodynamics team thus finds itself operating not only in urgent conditions but also in dangerous conditions due to the presence of ionizing radiation. Nursing and technical staff need additional skills to be able to take on roles from basic care to emergency electric shock resuscitation. The purpose of this work is to illustrate the phases of the activity that stabilize the treatment in the hemodynamics room from the acute phase to the patient.
161 Biosensor in cardiology. T-care project: a preliminary study on innovative wearable non-invasive telemonitoring system
Authors: Amati Francesca , Ezio Santobuono Vincenzo , Bozza Nicola , Latorre Maria , Memeo Riccardo , Favale Stefano
Published: December 2021

The demographic trend evolution and the modification of health needs highlight the requirement for a novel organization of the healthcare system. Telemedicine is a technological tool that allows a knockdown of geographic barriers being useful in the management of remote patient assistance. Telemedicine is roughly applied in different cardiology’s areas, from telemetric to implantable devices (loop recorders) in order to monitor cardiac rate, cardiac rhythm variations, and the onset of arrhythmic events. The aim of the present study is to assess the validity of wearable devices (T-shirt equipped with biosensors and bands with photopletimographic system) in monitoring EKG, cardiac rate, and pulse oximetry. We enrolled 38 patients, 25 of whom admitted to the Cardiology Unit, University of Bari. Main characteristics of the sample are listed in Table 1.

The difference between traditional monitoring system and wearable biosensors in not statistically significant as shown in Figure 1; therefore the devices tested in this study show a satisfying level of reliability in monitoring cardiac rate, pulse oximetry, QT interval, QRS complexes, and onset of arrhythmic events. However, alerts produced by arrhythmias different from atrial fibrillation are not completely reliable; moreover, the software and the diagnostic algorithm need to be optimized for motion artefacts. For these reasons, results need to be reproduced on a large cohort of patients.
269 Management of cardiac implantable electronic device follow-up in COVID-19 pandemic: lessons learned during Italian lock down
Authors: Piro Agostino , Magnocavallo Michele , Vetta Giampaolo , Bernardini Alessia , Mariani Marco Valerio , Chimenti Cristina , Giunta Giuseppe , Trivigno Sara , Di Iorio Martina , Mei Maria Chiara , Severino Paolo , Straito Martina , Iannucci Gino , Neccia Matteo , Rocca Domenico Giovanni Della , Manzi Giovanni , Quaglione Raffaele , Natale Andrea , Fedele Francesco , Lavalle Carlo
Published: December 2021

Aims

Remote monitoring (RM) has significantly transformed the standard of care for patients with cardiac electronic implantable devices. It provides easy access to valuable information, such as arrhythmic events, acute decompensation manifestations, and device-related issues, without the need of in-person visits.

Methods and results

Starting 1 March, 332 patients were introduced to an RM programme during the Italian lockdown to limit the risk of in-hospital exposure to severe acute respiratory syndrome-coronavirus-2. Patients were categorized into two groups based on the modality of RM delivery [home (n = 229) vs. office (n = 103) delivered]. The study aimed at assessing the efficacy of the new follow-up protocol, assessed as mean RM activation time (AT), and the need for technical support. In addition, patients’ acceptance and anxiety status were quantified via the Home Monitoring Acceptance and Satisfaction Questionnaire and the Generalized Anxiety Disorder 7-item scale. AT time was less than 48 h in 93% of patients and 7% of them required further technical support. Despite a higher number of trans-telephonic technical support in the home-delivered RM group, mean AT was similar between groups (1.33 ± 0.83 days in home-delivered vs. 1.28 ± 0.81 days in office-delivered patients; P = 0.60). A total of 28 (2.5%) urgent/emergent in-person examinations were required. A high degree of patient satisfaction was reached in both groups whereas anxiety status was higher in the office-delivered group.

Conclusions

The adoption of RM resulted in high patient satisfaction, regardless of the modality of modem delivery; nonetheless, in-office modem delivery was associated with a higher prevalence of anxiety symptoms.
731 Single centre experience tricuspid valve transcatheter edge to edge repair
Authors: Paolucci Luca , Nusca Annunziata , Cammalleri Valeria , Nobile Edoardo , De Filippis Aurelio , Vitez Luka , Carpenito Myriam , Ricottini Elisabetta , Melfi Rosetta , Cocco Nino , Mangiacapra Fabio , Gallo Paolo , Grigioni Francesco , Ussia Gian Paolo
Published: December 2021

Aims

Severe tricuspid valve regurgitation (TVR) is critically associated with an increased risk of morbidity and mortality, surgical treatment is limited by high perioperative risk. In these patients, transcatheter edge to edge valve repair (TEER) is progressively recognized as an effective treatment strategy. The aim of this work is to report the single centre experience procedural results and clinical outcomes in ‘real-world’ patients suffering TVR treated with the TriClip™ device (Abbott Vascular, Santa Clara, California).

Methods

From January up to July 2021, we screened 30 patients with severe TR, among which 8 were treated with TEER. All patients underwent cardiac computerized tomography and both transesophageal and transthoracic echocardiography, with the purpose to identify a dedicated grasping strategy. TEER was performed through right common femoral vein access, advancing a 24 F steerable guiding catheter (SGC) in the right atrium. Following, the TriClip delivery system was advanced and positioned over the valve centroid and, once oriented, the clip was opened. Under fluoroscopic and transesophageal monitoring, the clip was advanced in the right ventricle and pulled back to grasp the target leaflets. Following echocardiographic control, the clip was released.

Results

Procedural success, defined as a significative reduction of the regurgitation’s severity, was achieved in all patients. No procedural or in-hospital adverse events were reported. At 30 days follow-up, all patients were alive and no further hospitalizations occurred.

Conclusions

In our single centre experience, TEER appeared to be a valid and feasible therapeutic option in patients with severe TVR. Multicentre prospective studies are mostly needed to assess the long terms outcomes of TEER in these patients, with the purpose to introduce in the clinical practice a valid alternative to the highly risk surgical option.
341 Observational multicentre study on effectiveness and tolerability of Alirocumab in real world, the OMERO study: interim data from the first 699 patients
Authors: Luigi Catapano Alberico , Maggioni Aldo Pietro , Rossi Francesco , Tirone Giampaolo , Notarianni Lucia , Agnelli Giancarlo , Cesaro Arturo
Published: December 2021

Aims

OMERO is a prospective study, aimed to assess the long-term effectiveness, tolerability, and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-i), in the real life in Italy. The study is planned to include 800 patients, from 40 Italian sites, treated with alirocumab on top of standard lipid lowering therapy.

Methods and results

This analysis concerns 699 (out of 800) patients with all data available: 65.5% male; mean age 60.6 ± 11.09 years; 29.6% with HeFH in primary prevention; 70.4% in secondary prevention (with/without HeFH). Before ALI administration, 461 patients (66%) were treated with statins while 231 (33%) reported statin intolerance, that resulted in the statin discontinuation. Mean baseline LDL-C was 161.5 ± (53.07) mg/dl. Based on clinical judgement, ALI was initially prescribed at 75 mg Q2W dosing regimen in 60.80% of participants, whereas the remainder received 150 mg Q2W. At V1 57 patients (89.06%) switch from 75 mg Q2W to 150 mg Q2W and 7 patients (10.94%) from 150 mg Q2W to 75 mg Q2W. LDL-C level reduction from baseline (before ALI administration) to 6 months from the study enrolment (V1), was −45% (V1: mean LDL-C was 73.5 ± 45.70 mg/dl). LDL-C levels at V1 by participant category are shown in Figure 1. The rate of patients with at least one adverse event was 25.6% (of which SAE 7.4%); the rate of patients with at least one related adverse reaction to treatment was 3.8% none of them were serious.

Conclusions

OMERO confirmed in clinical practice the results observed in trials: a significant reduction of LDL-C was observed with ALI 75/150 mg Q2W in participants at high CV risk with or without HeFH. ALI was generally well tolerated.
809 Frequency and determinants of haemoglobin drop without overt bleeding in patients undergoing transcatheter aortic valve replacement
Authors: Carabetta Nicole , Sorrentino Sabato , Boccuto Fabiola , Bellantoni Antonio , Giordano Salvatore , Cacia Michele Antonio , Polimeni Alberto , Leo Isabella , Varano Ylenia , Augusto Florinda Maria , Mongiardo Annalisa , De Rosa Salvatore , Indolfi Ciro , Spaccarotella Carmen
Published: December 2021

Aims

Post-procedural bleedings have a significant impact on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). Unfortunately, the source of these bleedings is often undetermined, causing difficulties in diagnosis and related treatment. Furthermore, the frequency and determinants of ‘non-overt’ bleeding are largely lacking in TAVR studies. Accordingly, in this analysis, we aimed to assess the frequency and determinants of haemoglobin drop without overt bleeding in patients undergoing TAVR.

Methods

Patients undergoing TAVR at Magna Graecia University in Catanzaro from September 2008 to November 2020 were included in this study. Post-procedural haemoglobin (Hb) drop was calculated subtracting the lowest value observed after the procedure to the one obtained at admission (Hb drop). The association between baseline clinical and procedural variables with Hb drop was investigated with a linear regression model.

Results

Out of 407 patients undergoing TAVR at our institution, 119 (29.2%) were excluded because experiencing overt bleeding, red blood cells transfusion, were treated with only balloon angioplasty, or for procedural unsuccess. Among the 288 patients included in the final analysis, 239 (83.0%) were older than 74 y.o., 148 (51.4%) were female, 94 (32.6%) were diabetics, and 69 (24.0%) had CKD. All the patients were deemed at intermediate/high operatory risk and treated using the transfemoral approach. After TAVR, Hb significantly decreased (12.6 ± 1.6 g/dL to 9.7 ± 1.3 g/dL, P < 0.001), with an absolute mean reduction of 2.9 ± 1.23 g/dL 126 patients (43.8%) had Hb drop ≥ 3 g/dL, while 11 (3.8%) had Hb drop ≥ 5 g/dL. The table below summarizes the determinants of Hb drop. Among them, the new generation of self-expandable and balloon-expandable devices were associated with a lower post-procedural Hb drop compared to the previous generation of self-expandable devices, alongside, higher body mass index and hypertension.

Conclusions

Post-procedural reduction of Hb without overt bleeding or RBC transfusion is frequent, involving almost half of the patients undergoing TAVR. The introduction in clinical practice of new-generation valve devices is significantly associated with a reduction of this adverse event. However, further and thorough investigation should be accomplished to reclassify this large part of patients into a well-defined category.
817 Potent P2Y12 inhibitors in elderly population, insigth from praise registry
Authors: Elia Edoardo , D’Ascenzo Fabrizio , Breviario Susanna , Bruno Francesco , Marengo Giorgio , De Filippo Ovidio , Conrotto Federico , Maria De Ferrari Gaetano
Published: December 2021

Background

The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly patients with acute coronary syndrome (ACS) remains unclear.

Methods

All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones.

Results

4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16±3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p=0.94 and HR 0.38; 0.14-1.04, p=0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p=0.03 and HR 0.43; 0.14-0.89, p=0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p=0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p=0.04 and HR 2.36; 1.02-5.52, p=0.04, all 95%CI) with neutral effect on NACE and MACE.

Conclusions

In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older. 817 Figure 1
The recombination landscapes of spiny lizards (genusSceloporus)
Authors: Versoza Cyril J , Rivera Julio A , Rosenblum Erica Bree , Vital-García Cuauhcihuatl , Hews Diana K , Pfeifer Susanne P
Published: December 2021

Despite playing a critical role in evolutionary processes and outcomes, relatively little is known about rates of recombination in the vast majority of species, including squamate reptiles—the second largest order of extant vertebrates, many species of which serve as important model organisms in evolutionary and ecological studies. This paucity of data has resulted in limited resolution on questions related to the causes and consequences of rate variation between species and populations, the determinants of within-genome rate variation, as well as the general tempo of recombination rate evolution on this branch of the tree of life. In order to address these questions, it is thus necessary to begin broadening our phylogenetic sampling. We here provide the first fine-scale recombination maps for two species of spiny lizards, Sceloporus jarrovii and Sceloporus megalepidurus, which diverged at least 12 Mya. As might be expected from similarities in karyotype, population-scaled recombination landscapes are largely conserved on the broad-scale. At the same time, considerable variation exists at the fine-scale, highlighting the importance of incorporating species-specific recombination maps in future population genomic studies.
Barcoded reciprocal hemizygosity analysis via sequencing illuminates the complex genetic basis of yeast thermotolerance
Authors: Abrams Melanie B , Chuong Julie N , AlZaben Faisal , Dubin Claire A , Skerker Jeffrey M , Brem Rachel B
Published: December 2021

Decades of successes in statistical genetics have revealed the molecular underpinnings of traits as they vary across individuals of a given species. But standard methods in the field cannot be applied to divergences between reproductively isolated taxa. Genome-wide reciprocal hemizygosity mapping (RH-seq), a mutagenesis screen in an interspecies hybrid background, holds promise as a method to accelerate the progress of interspecies genetics research. Here, we describe an improvement to RH-seq in which mutants harbor barcodes for cheap and straightforward sequencing after selection in a condition of interest. As a proof of concept for the new tool, we carried out genetic dissection of the difference in thermotolerance between two reproductively isolated budding yeast species. Experimental screening identified dozens of candidate loci at which variation between the species contributed to the thermotolerance trait. Hits were enriched for mitosis genes and other housekeeping factors, and among them were multiple loci with robust sequence signatures of positive selection. Together, these results shed new light on the mechanisms by which evolution solved the problems of cell survival and division at high temperature in the yeast clade, and they illustrate the power of the barcoded RH-seq approach.
Populations, Traits, and Their Spatial Structure in Humans
Authors: Sohail Mashaal , Izarraras-Gomez Alan , Ortega-Del Vecchyo Diego
Published: December 2021

The spatial distribution of genetic variants is jointly determined by geography, past demographic processes, natural selection, and its interplay with environmental variation. A fraction of these genetic variants are “causal alleles” that affect the manifestation of a complex trait. The effect exerted by these causal alleles on complex traits can be independent or dependent on the environment. Understanding the evolutionary processes that shape the spatial structure of causal alleles is key to comprehend the spatial distribution of complex traits. Natural selection, past population size changes, range expansions, consanguinity, assortative mating, archaic introgression, admixture, and the environment can alter the frequencies, effect sizes, and heterozygosities of causal alleles. This provides a genetic axis along which complex traits can vary. However, complex traits also vary along biogeographical and sociocultural axes which are often correlated with genetic axes in complex ways. The purpose of this review is to consider these genetic and environmental axes in concert and examine the ways they can help us decipher the variation in complex traits that is visible in humans today. This initiative necessarily implies a discussion of populations, traits, the ability to infer and interpret “genetic” components of complex traits, and how these have been impacted by adaptive events. In this review, we provide a history-aware discussion on these topics using both the recent and more distant past of our academic discipline and its relevant contexts.
Validation of the 3M™ Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) for the Detection of Shiga Toxin Gene (stx and eae) in Fresh Raw Beef Trim, Fresh Raw Ground Beef and Fresh Spinach: AOAC Performance Tested MethodSM 071902
Authors: Rosauer Micki L , Barnes Christina , Silbernagel Karen M , Koch Kateland M
Published: December 2021

Background

The 3M™ Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) method is based on gene amplification using real time loop-mediated isothermal amplification with the 3M Molecular Detection System for the rapid and specific detection of Shiga toxin gene (stx1 and/or stx2) and intimin gene (eae) from Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC) in enriched foods.

Objective

The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) method was evaluated for AOAC®  Performance Tested MethodsSM certification.

Methods

Matrix studies, inclusivity/exclusivity, robustness, product stability, and lot-to-lot variability testing were conducted to assess the method’s performance.

Results

The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) demonstrated equivalent results to the US Department of Agriculture–Food Safety and Inspection Service Microbiology Laboratory Guidebook 5C.00 for fresh raw beef trim and fresh raw ground beef, and to the US Food and Drug Administration Bacteriological Analytical Manual Chapter 4A for fresh spinach. The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) detected 50 of 50 E. coli strains with stx1 and/or stx2 genes, and the eae gene, and detected zero of 40 strains from the exclusivity panel. Robustness testing indicated that small variations in critical test parameters did not adversely affect the assay’s performance. Product consistency and stability testing demonstrated no differences between the lots evaluated.

Conclusion

The data collected demonstrates that the 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) is a reliable method for the rapid and specific detection of STEC in raw beef trim, raw ground beef, and spinach.

Highlights

The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) method is suitable for the rapid and specific detection of STECs in raw beef trim, raw ground beef, and spinach.
Radio Galaxy Zoo: giant radio galaxy classification using multidomain deep learning
Authors: Tang H , Scaife A M M , Wong O I , Shabala S S
Published: December 2021

In this work we explore the potential of multidomain multibranch convolutional neural networks (CNNs) for identifying comparatively rare giant radio galaxies from large volumes of survey data, such as those expected for new generation radio telescopes like the SKA and its precursors. The approach presented here allows models to learn jointly from multiple survey inputs, in this case NVSS and FIRST, as well as incorporating numerical redshift information. We find that the inclusion of multiresolution survey data results in correction of 39 per cent of the misclassifications seen from equivalent single domain networks for the classification problem considered in this work. We also show that the inclusion of redshift information can moderately improve the classification of giant radio galaxies.
A new model for simulating circumstellar dynamics in young stellar clusters
Authors: Wiśniowski T , Rickman H , Wajer P
Published: December 2021

Simulations of angular momentum transfer from a surrounding star cluster to distant planetesimals orbiting around a cluster member have been used since more than two decades to study the formation of small body populations in the outskirts of the Solar system (Oort Cloud and sednoids). We present a new model for these interactions, for the first time combining two features of earlier works: (1) a self-consistent treatment of cluster evolution based on N-body simulations, and (2) a treatment of circumstellar dynamics as resulting from a combination of a smooth tidal field representing the whole cluster and close encounters by individual cluster members. The model is expected to be both flexible, accurate, and efficient in terms of CPU time and hence a suitable tool when simulating large or long-lived clusters or when many independent runs are needed for statistical significance. We describe the model in detail and give examples of its outputs. These are of relevance not only for the perihelion extraction of small bodies but also for the stability properties of young or nascent planetary systems or protoplanetary discs.
Supervised learning with word embeddings derived from PubMed captures latent knowledge about protein kinases and cancer
Authors: Ravanmehr Vida , Blau Hannah , Cappelletti Luca , Fontana Tommaso , Carmody Leigh , Coleman Ben , George Joshy , Reese Justin , Joachimiak Marcin , Bocci Giovanni , Hansen Peter , Bult Carol , Rueter Jens , Casiraghi Elena , Valentini Giorgio , Mungall Christopher , Oprea Tudor I , Robinson Peter N
Published: December 2021

Inhibiting protein kinases (PKs) that cause cancers has been an important topic in cancer therapy for years. So far, almost 8% of >530 PKs have been targeted by FDA-approved medications, and around 150 protein kinase inhibitors (PKIs) have been tested in clinical trials. We present an approach based on natural language processing and machine learning to investigate the relations between PKs and cancers, predicting PKs whose inhibition would be efficacious to treat a certain cancer. Our approach represents PKs and cancers as semantically meaningful 100-dimensional vectors based on word and concept neighborhoods in PubMed abstracts. We use information about phase I-IV trials in ClinicalTrials.gov to construct a training set for random forest classification. Our results with historical data show that associations between PKs and specific cancers can be predicted years in advance with good accuracy. Our tool can be used to predict the relevance of inhibiting PKs for specific cancers and to support the design of well-focused clinical trials to discover novel PKIs for cancer therapy.
A Rare Bird: Diagnosis of Psittacosis Meningitis by Clinical Metagenomic Next-Generation Sequencing
Authors: Davar K , Wilson M R , Miller S , Chiu C Y , Vijayan T
Published: December 2021

Psittacosis is a zoonotic infectious disease caused by the transmission of Chlamydia psittaci; it often presents as a pulmonary infection but rarely as disseminated disease. Because diagnoses of psittacosis are often underreported due to infrequent pathogen-specific testing, clinical metagenomic next-generation sequencing may be helpful to diagnose such an uncommon syndrome.
Circulation of Non-SARS-CoV-2 Respiratory Pathogens and Coinfection with SARS-CoV-2 Amid the COVID-19 Pandemic
Authors: Uhteg Katharine , Amadi Adannaya , Forman Michael , Mostafa Heba H
Published: December 2021

Background

Our understanding of the cocirculation of infrequently targeted respiratory pathogens and their contribution to symptoms during the coronavirus disease 2019 (COVID-19) pandemic is currently limited. This research aims at (1) understanding the epidemiology of respiratory pathogens since the start of the pandemic, (2) assessing the contribution of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/influenza/respiratory syncytial virus (RSV) respiratory pathogens to symptoms, and (3) evaluating coinfection rates in SARS-CoV-2-positive patients, both vaccinated and unvaccinated.

Methods

Retrospective analysis of respiratory pathogens identified by the Johns Hopkins Diagnostic Laboratory between December 2019 and October 2021 was performed. In addition, we assessed the contribution of respiratory pathogens other than SARS-CoV-2 to symptomatic disease by retesting 2 cohorts of specimens that were (1) collected from symptomatic patients and (2) received limited respiratory pathogen testing. The first cohort was patients who tested negative by the standard-of-care SARS-CoV-2/influenza/RSV testing. The second was a cohort of SARS-CoV-2-positive, symptomatic, fully COVID-19 immunized and unimmunized patients.

Results

Between December 2019 and October 2021, a total of 11 806, 62 829, and 579 666 specimens were tested for an extended respiratory panel, influenza/RSV with or without SARS-CoV-2 panel, or SARS-CoV-2, respectively. Positivity rates of different targets differed between different months and were impacted by the COVID-19 pandemic. The SARS-CoV-2-negative cohort had 8.5% positivity for other respiratory pathogens that included primarily enterovirus/rhinovirus (5.8%). In the SARS-CoV-2-positive cohort, no other respiratory pathogens were detected.

Conclusions

The COVID-19 pandemic impacted the circulation of certain respiratory pathogens. Other respiratory viral pathogens were associated with symptomatic infections; however, coinfections with SARS-CoV-2 were highly uncommon.