bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acidic environments trigger intracellular H+-sensing FAK proteins to re-balance sarcolemmal acid–base transporters and auto-regulate cardiomyocyte pH
Authors: Wilson Abigail D , Richards Mark A , Curtis M Kate , Gunadasa-Rohling Mala , Monterisi Stefania , Loonat Aminah A , Miller Jack J , Ball Vicky , Lewis Andrew , Tyler Damian J , Moshnikova Anna , Andreev Oleg A , Reshetnyak Yana K , Carr Carolyn , Swietach Pawel 
Published: December 2021

Abstract

Aims
In cardiomyocytes, acute disturbances to intracellular pH (pHi) are promptly corrected by a system of finely tuned sarcolemmal acid–base transporters. However, these fluxes become thermodynamically re-balanced in acidic environments, which inadvertently causes their set-point pHi to fall outside the physiological range. It is unclear whether an adaptive mechanism exists to correct this thermodynamic challenge, and return pHi to normal.

Methods and results
Following left ventricle cryo-damage, a diffuse pattern of low extracellular pH (pHe) was detected by acid-sensing pHLIP. Despite this, pHi measured in the beating heart (13C NMR) was normal. Myocytes had adapted to their acidic environment by reducing Cl−/HCO3− exchange (CBE)-dependent acid-loading and increasing Na+/H+ exchange (NHE1)-dependent acid-extrusion, as measured by fluorescence (cSNARF1). The outcome of this adaptation on pHi is revealed as a cytoplasmic alkalinization when cells are superfused at physiological pHe. Conversely, mice given oral bicarbonate (to improve systemic buffering) had reduced myocardial NHE1 expression, consistent with a needs-dependent expression of pHi-regulatory transporters. The response to sustained acidity could be replicated in vitro using neonatal ventricular myocytes incubated at low pHe for 48 h. The adaptive increase in NHE1 and decrease in CBE activities was linked to Slc9a1 (NHE1) up-regulation and Slc4a2 (AE2) down-regulation. This response was triggered by intracellular H+ ions because it persisted in the absence of CO2/HCO3− and became ablated when acidic incubation media had lower chloride, a solution manoeuvre that reduces the extent of pHi-decrease. Pharmacological inhibition of FAK-family non-receptor kinases, previously characterized as pH-sensors, ablated this pHi autoregulation. In support of a pHi-sensing role, FAK protein Pyk2 (auto)phosphorylation was reduced within minutes of exposure to acidity, ahead of adaptive changes to pHi control.

Conclusions
Cardiomyocytes fine-tune the expression of pHi-regulators so that pHi is at least 7.0. This autoregulatory feedback mechanism defines physiological pHi and protects it during pHe vulnerabilities.
The US Context of the Restatement of the Law (Fourth): The Foreign Relations Law of the United States
Authors: Stephan Paul 
Published: December 2021

Abstract
This article describes the creation and development of the Restatement of the Law (Fourth): The Foreign Relations Law of the United States from the perspective of its coordinating reporter. The article first describes how the American Law Institute goes about creating restatements of the law, emphasizing aspects of the process that a European audience might find unfamiliar. It looks at aspects of the US legal system, especially the significant role of the judiciary as authors of law, and explains how this role shapes a document that has US judges as one of its significant audiences. It then discusses how conflict over the content of foreign relations law and the role of international law in US domestic law affects the Restatement and how the reporters seek to navigate these troubled waters. Finally, it explores the areas where the new Restatement (Fourth) parts company with its famous predecessor, the Restatement (Third), supervised by the late professor Louis Henkin. The article argues that the changes represent two things: a transformation of the world of foreign relations in the 35 years since the earlier work and a corresponding move towards modesty on the part of the professors who made this Restatement.
76 Right mini-thoracotomy surgical Cox-maze (left atrial lesion) vs. catheter ablation using contact force-sensing technology in patients with persistent atrial fibrillation
Authors: D'Ambrosio Gabriele , Raffa Santi , Romano Silvio , Alothman Obaida , Borisov Georgi , Karam Issa , Thomas Kuntze , Geller J. Christoph 
Published: December 2021

Abstract

Aims
Pulmonary vein isolation (PVI) often is not sufficient in patients (pts) with persistent atrial fibrillation (AF). Substrate modification (SM) by catheter ablation (CA) of low-voltage zones (LVZ) has yielded favourable results, but those studies were performed before the introduction of contact force (CF) sensing technology. Surgical ablation (SA) studies support the hypothesis that empiric bi-atrial linear ablation (Cox Maze IV procedure) is able to improve success, but there is less data on outcome of patients undergoing left atrial (LA) linear lesions alone. In current guidelines, both CA and SA have Class IIa indication in pts with persistent AF. In this single-centre retrospective study, we analysed the long-term outcomes of CA and SA in pts with persistent AF.

Methods and results
In the CA group (Figure 1), pts underwent PVI and additional SM in the presence of LVZ (roof line and supero-septal line) using TactiCath™ or SmartTouch™ ablation catheters aiming at contact values ≥10 g &lt; 20 g and FTI &gt;400 g/s. Ablation was performed in a temperature-controlled fashion with energy of 30 W except at the posterior wall (20–25 W). In the SA group (Figure 2), pts underwent ablation procedure (creation of a pure LA endocardial lesion set consistent with the Cox Maze IV) performed by a right mini-thoracotomy approach using the Atricure™ cryoablation probe, a left atrial appendage (LAA) epicardial exclusion using the Atriclip™ system, and mitral valve repair in the presence of severe mitral valve regurgitation. No right atrial lesions were created. 196 pts were included. 120 pts underwent CA [median age: 65 (58–72) years, median LA volume index (LAVI): 66 (56–75) ml/m2], in pts with LVZs PVI + SM was performed [bidirectional block of lines in 100%]. 76 pts underwent SA [median age: 64 (58–74) years, median LAVI 90 (78–103) ml/m2], in 42 pts a mitral valve repair was performed. At 24 months (figure), 89% and 68% of pts were free of AF in the SA and CA group, respectively, mainly without antiarrhythmic drugs (92% SA group and 89% CA group).

Conclusions
In patients with persistent AF, SA performed by a right mini-thoracotomy approach with linear lesions limited to LA leads to excellent 2-year freedom from AF despite significantly larger LAVI compared with the CA group. LAA epicardial exclusion likely contributed to surgical efficacy by eliminating the LAA as trigger/driver.
655 The valuable interaction among cardiac surgeon and electrophysiologist for transvenous rotational mechanical lead extraction
Authors: Migliore Federico , Tarzia Vincenzo , Bernardo Dall’Aglio Pietro , Falzone Pasquale Valerio , Iliceto Sabino , Gerosa Gino 
Published: December 2021

Abstract

Aims
Recent studies have shown that evolution RL bidirectional rotational mechanical sheath (Cook Medical, USA) is an effective and safe technique for transvenous lead extraction (TLE). We reported our experience with the bidirectional rotational mechanical tools using a multidisciplinary approach highlighting the value of a joint cardiac surgeon and electrophysiologist collaboration.

Methods and results
The study population comprised 84 patients (77% male; mean age 65 ± 18 years) undergoing TLE. After multidisciplinary evaluation, a combined procedure was considered. The main indication for TLE was infection in 54 cases (64%).Overall, 152 leads were extracted with a mean implant duration of 94 ± 63 months (range: 6–421). Complete procedural success rate, clinical success rate, and lead removal with clinical success rate were 91.6% (77/84), 97.6% (82/84), and 98.6% (150/152), respectively. Eighteen combined procedures were performed in 12 patients (14%), such as ‘hybrid approach’ (n = 2) or TLE concomitant to: (i) transcatheter aspiration procedure for large vegetation (n = 8); (ii) left ventricular assistance device implantation as bridge to cardiac transplantation (n = 1); (iii) permanent pacing with epicardial leads (n = 6); and (iv) tricuspid valve replacement (n = 1).One major complication (1.2%) and 11 (13%) minor complications were encountered. No injury to the superior vena cava occurred and no procedure-related deaths were reported. During a mean time follow-up of 21 ± 18 months, 17 patients (20%) died. They were more often diabetics (P = 0.02), and they underwent TLE more often for infection (P = 0.004).

Conclusions
Our results support the finding that excellent outcomes can be achieved in performing TLE of chronically implanted leads by using the evolution RL bidirectional rotational mechanical sheath and a multidisciplinary team approach involving both electrophysiologist and cardiac surgeon as first line operators.
707 Transvenous radiofrequency ablation of epicardial posterior-septal accessory pathways in children with WPW syndrome: can technology and imaging innovations improve the outcome?
Authors: Pazzano Vincenzo , Tamborrino Pietro Paolo , Di Mambro Corrado , Silvetti Massimo Stefano , Drago Fabrizio 
Published: December 2021

Abstract

Aims
The aim of the study was to analyse our recent single-centre experience about epicardial posterior-septal accessory pathways transcatheter ablation in children and young patients using radiofrequency through the coronary sinus, in order to understand which mapping and ablation strategy is associated with higher success rate and safety.

Methods and results
We reviewed all the cases of ablation of overt accessory pathways (in Wolff–Parkinson–White syndrome) with epicardial posterior-septal localization performed in children or young patients at our institution in the last 5 years. Twenty-two paediatric patients (mean age: 13 ± 3 years) with epicardial posterior-septal accessory pathways (15 in coronary sinus and 7 in the Middle Cardiac Vein) underwent radiofrequency transcatheter ablation with CARTO 3TM. Acute success rate was 77%. No patient was lost to follow-up (mean time 14.4 ± 9 months). The recurrence rate was 18%. Two patients underwent a successful redo-procedure; the overall long-term success rate was 68%. NAVISTAR® catheter presented the highest acute success rate in the coronary sinus. NAVISTAR SMARTTOUCH® was the only catheter that did not present recurrences after the acute success and it was successfully used in two patients previously unsuccessfully treated with a NAVISTAR THERMOCOOL®. Integration with angio-CT of coronary sinus branches obtained with CARTOMERGE was associated with higher success rate in patients with a previous failed ablation attempt.

Conclusions
Epicardial posterior-septal accessory pathways can be successfully treated with transvenous radiofrequency ablation in more than half of the cases in children/young patients. Acute success rate does not seem to depend on catheters used but contact-force catheter seems to be useful in cases with recurrences. Image integration with cardiac-CT reconstruction of coronary sinus branches anatomy can be useful to better guide ablation in case of previously failed attempts.
537 Oversensing due to micro-air bubbles leading to inappropriate shocks in patient with subcutaneous implantable cardioverter defibrillator
Authors: Seganfreddo Francesca , Golino Michele , Ceriani Francesca , Matteo Federica , Morello Matteo , Licciardello Claudio , Marazzato Jacopo , Vilotta Manola , Caravati Fabrizio , De Ponti Roberto 
Published: December 2021

Abstract

Aims
Subcutaneous air has been reported as uncommon cause of early device malfunction after implantation of subcutaneous implantable cardioverter defibrillator (S-ICD).

Methods and results
A 43-year-old man was admitted to our hospital due to syncopal episodes. During a brain computed tomography (CT), he was resuscitated from cardiac arrest due to ventricular fibrillation. Further investigations excluded ischaemic heart disease and cardiac magnetic resonance showed signs of prior myocarditis. After successful screening, an S-ICD was inserted for secondary prevention using the standard technique. The chest X-ray excluded acute post-procedural complications. Three days after implantation, he experienced two inappropriate shocks while conscious. Device interrogation revealed frequent high-amplitude signals followed by two shocks (Figure 1A and B) that could be interpreted as oversensing. During provocative maneuvers on the generator case, minimal and intermittent noise only on the secondary sensing vector was observed. Lateral and antero-posterior chest X-ray excluded subcutaneous air. However, the general agreement based on previous reports was that oversensing as observed in Figures 1A and B was typical for noise due to micro-air bubbles in the connection between the lead and the generator case. As a consequence, the sensing vector was successfully changed and no other inappropriate shocks were observed during follow-up.

Conclusions
Entrapped micro-air bubbles in the connection between the leads and the generator case can cause inappropriate shocks in the early period after S-ICD implantation. Timely recognition of this complication is important to prevent inappropriate shocks. It can occur shortly after the procedure even if the intra-procedural parameters were normal and chest X-ray excluded acute complications. As demonstrated in our case, the device can be reprogrammed using another sensing vector to solve these oversensing problems.
549 The role of conventional and speckle tracking echocardiography in the evaluation of leadless endocardial pacing with Micra-AV
Authors: Soldato Nicolò , Bozza Nicola , Basile Paolo , Pontone Gianluca , Siena Paola , Memeo Riccardo , Santobuono Vincenzo Ezio , Carella Maria Cristina , Favale Stefano , Guaricci Andrea Igoren 
Published: December 2021

Abstract

Aims
Micra-AV pacing system is a leadless pacemaker (LP) implanted in the right ventricle which can provide atrio-ventricular (AV) synchronous pacing. Echocardiographic data assessing left ventricle contractility 24–48 h after Micra AV implantation are lacking. To evaluate via conventional echocardiography and speckle-tracking echocardiography (STE), which was the best pacing modality (VVI vs. VDD) able to ensure the most efficient hemodynamic performance assessed by left ventricle ejection fraction (LF-EF) and global longitudinal strain (GLS).

Methods and results
We studied nine patients with high degree AV-block, enrolled in our Institution in a range of time of 5 months. All patients had first degree AV block (PQ interval between 160 and 340 ms). They were considered suitable candidates for MICRA-AV implantation according to current guidelines. Both LF-EF and GLS were performed 24–48 h after device implantation by two experienced echocardiographic physicians. The mean age of the population was 79 ± 8 years (8 were male, 89%). Risk factors more represented were hypertension and dyslipidaemia. The maximum PQ interval was 256 ± 51 ms. VDD pacing modality allows better LV-EF values than those obtained with a VVI stimulation (with a difference that was statistically significant difference, P-value = 0.008). Similarly, we obtained better GLS values during VDD pacing as respect to VVI (P-value = 0.008).

Conclusions
Left ventricle ejection fraction and LV-GLS improve early after leadless MICRA-AV implantation during VDD as compared to VVI pacing modality.
726 Outcomes of ischaemic stroke in patients with atrial fibrillation
Authors: Strisciuglio Teresa , Pergolae Valerio , Ammirati Giuseppe , Addeo Lucio , Todde Gaetano , Esposito Giovanni , Rapacciuolo Antonio 
Published: December 2021

Abstract

Aims
Atrial fibrillation (AF) increases the risk of ischaemic strokes (IS) and is associated with a more severe neurological impairment. We sought to investigate whether AF also impacts the neurological recovery and whether patients with AF have a different response to the treatment.

Methods and results
Data of patients admitted to the Stroke Unit of our institution from January to December 2020 were retrieved from the local database. The stroke severity was calculated by mean of the National Institute of Health Stroke Scale (NIHSS) at hospital admission (NIHSSad), at 24 h (NIHSS24) and at discharge (NIHSSdis). The functional capacity was assessed by the modified Rankin score (mRS). As for the neurological recovery, this was assessed by the delta NIHSS at 24 h (Δ24 = NIHSS24−NIHSSad) and at discharge (Δdis = NIHSSdis−NIHSSad). Out of 545 patients with IS 64 had known history of AF or were admitted with AF. Patients with AF had higher NIHSSad (13.9 ± 7 vs. 8.5 ± 7; P &lt; 0.001) and NIHSS24 (9.6 ± 8 vs. 6.4 ± 7; P = 0.007) than patients without, however the neurological improvement was greater (Δdis −7.4 ± 9 vs. −3.4 ± 6; P = 0.002), indeed the NIHSSdis was similar (4.2 ± 5 vs. 4.2 ± 6; P = 0.98). Patients with AF also had a more impaired mRS before the ischaemic event and at discharge (2.4 ± 1.9 vs. 1.6 ± 1.7, P = 0.02; 1.2 ± 1.2 vs. 0.4 ± 0.9, P &lt; 0.001). Among AF patients with CHADVASC ≥ 3, 34% of them were taking antiplatelet therapy, 31% anticoagulants, and 35% didn’t take any therapy. Of interest, no differences in the NIHSSad nor in the NIHSSdis were found between them and neither in the Δdis. As for the treatment of AF patients, no differences in the neurological recovery were observed between those treated with intravenous thrombolysis and those not treated at all (Δdis 2.8 ± 5 vs. 2.8 ± 8, P = 1), whereas the Δdis was significantly higher in patients treated with mechanical thrombectomy (−11.7 ± 7, P = 0.007).

Conclusions
Patients with AF experience more severe stroke, however the neurological recovery is greater than in patients without the arrhythmia. The treatment with antiplatelets or anticoagulants before the event does not reduce the severity of the stroke and does not influence the improvement of the NIHSS at discharge. The mechanical thrombectomy is more effective in reducing the neurological impairment.
487 Instrumental evaluation of mild cognitive decline in hypertensive patients: the role of transcranial doppler
Authors: Junior Ferruzzi Germano , Visco Valeria , Loria Francesco , Donnarumma Sofia , Galasso Gennaro , Iaccarino Guido , Vecchione Carmine , Ciccarelli Michele 
Published: December 2021

Abstract

Aims
Hypertension is a known risk factor for stroke and vascular dementia. Recent studies have also shown that arterial hypertension represents a clear risk factor for mild cognitive decline and its evolution into Alzheimer’s disease. Really, mild cognitive decline significantly compromises the patient’s quality of life, reducing compliance with therapy and increasing mortality and hospitalization. Diagnosis of dementia is challenging and requires both ruling out potentially treatable underlying causes and ruling in a diagnosis of dementia subtype. Currently, this diagnosis is based on the execution of second-level investigations (e.g. neuroimaging), that are expensive and not always available. For this reason, we analysed a population of hypertensive patients without atrial fibrillation and/or cerebrovascular and/or neurodegenerative diseases, with the aim of verifying the existence of an association between cognitive impairment and flows on the middle cerebral artery (MCA).

Methods
We considered 33 hypertensive patients (age 64.90 co1.40 years; 72% male). Specifically, we considered anthropometric, clinical, laboratory, and echocardiographic parameters. Also, we administered: an accurate, sensitive, and specific screening test (QMCI) for the assessment of intermediate cognitive decline (MCI), which explores spatial and temporal orientation, registration, delayed recall, clock design, logical memory and verbal fluency in a concise time (5 min—score 0–100); a compliance questionnaire (Morisky medication adherence scale); a questionnaire on nutritional status (MNA). Finally, we recorded transcranial Doppler flows on the MCA.

Results
There is no QMCItot score compatible with dementia (&lt;20) among the patients analysed. A statistically significant inverse association emerged between total QMCI score and Morisky score (P &lt; 0.0001); in addition, the analysis of the different sections of the QMCI questionnaire showed: an inverse relationship between the Morisky score and the clock test (P 0.013), delayed recall (P 0.024) and logical memory (P 0.028). By comparing the Doppler velocities sampled on the MCA with QMCI scores, a statistically significant inverse relationship was found between mean flow velocity and orientation at QMCI (P 0.023), between PSV and orientation (P 0.017) and between EDV and orientation (P 0.049) (Figure).

Conclusions
In conclusion, our study demonstrates for the first time the existence of a significant association between the QMCI and the sampling of the MCA at the ultrasound Doppler. Studies on a larger population will be needed to confirm this association and to test the translational relevance, in particular to tailor therapeutic approach in patients with abnormal MCA Doppler.
435 Renal denervation in a patient with uncontrolled arterial hypertension secondary to polycystic kidney disease
Authors: Widmann Maddalena , Fezzi Simone , Castaldi Gianluca , Tavella Domenico , Pighi Michele , Ribichini Flavio Luciano 
Published: December 2021

Abstract

Aims
Autosomal dominant polycystic kidney disease (ADPKD) represents the most common inherited cause of chronic kidney disease. Typical manifestations of this condition include secondary hypertension, abdominal pain, haematuria and urinary tract infections. Despite the progressive increase in the use of antihypertensive therapy in patients with ADPKD in the last decades, reaching blood pressure target is often difficult in this setting due to the complex physiopathology of arterial hypertension in ADPKD. Catheter-based renal sympathetic denervation (RDN) represents nowadays a therapeutic strategy to approach resistant hypertension. Based on consistent results of several sham-controlled clinical trials, the evidence of safety and efficacy of this procedure is increasing, also in patients with multiple comorbidities including chronic kidney disease. Patients with ADPKD often develop chronic severe kidney-related pain, caused by distension of the renal capsule due to the expansion of the cysts. RDN was proposed to be an effective therapeutic option able to relieve loin pain.

Methods
A 49-year-old man affected by ADPKD was referred to our centre for resistant uncontrolled arterial hypertension, despite combined therapy with five antihypertensive drugs. He also complained about intense loin pain and 3 years earlier underwent two surgical interventions to remove voluminous renal cysts, that did not relieve chronic pain. His kidney function was moderately decreased at presentation, with progressive decline in the previous years. After a multi-disciplinary discussion with a nephrologist and algologist, the patient was proposed for RDN with the aim of lowering blood pressure and reducing pain. He was treated in July 2018, and after the procedure, was observed a better control of blood pressure but no benefits on pain. Because of the persistence of intractable loin pain, the patient was submitted to a second RDN in December 2018. Also, after this procedure, blood pressure declined remarkably, decreasing his need for antihypertensive medications without a significant worsening of kidney function. Unfortunately, no benefit on chronic pain was observed.

Results
ADPKD is characterized by the progressive bilateral development of focal renal cysts. Cardiovascular complications, mainly related to hypertension, are a major cause of morbidity and mortality for these patients. RDN could be a valid and safe therapeutic option for the treatment of secondary hypertension in this setting.