bluuebunny/crossref_metadata_2025 huggingface dataset:
AUTOIMMUNE MYOCARDITIS IN MELANOMA IMMUNOTHERAPY–COMPLEX CLINICA PRESENTATION AND ADVERSE THERAPEUTIC RESPONSE
Authors: Di Marino M , Galanti K , Testa S , Ricci M , Magnano R , Pezzi L , D‘Alleva A , Genovesi E , Forlani D , Vitulli P , Paloscia L , Gallina S , Di Marco M
Published: May 2024

A 68–year–old Caucasian female presented to the ED with cardiac chest pain and dyspnea. The patient had a history of arterial hypertension and was equipped with a biventricular pacemaker due to atrial fibrillation with low ventricular response. She had recently been diagnosed with metastatic melanoma and initiated treatment with nivolumab and ipilimumab two weeks prior. Troponin levels were elevated (700 ng/ml), and no ST–segment elevation was observed on the electrocardiogram (ECG). In suspicion of NSTEMI–ACS, coronary angiography was performed, revealing an intact epicardial coronary circulation without stenotic lesions. The echocardiogram showed borderline left ventricular systolic function (EF 50%), and the right ventricle exhibited initial signs of reduced systolic function (TAPSE, 15 mm; S RV, 9.5 m/s). The following day, there was a deterioration in hemodynamics and respiratory exchange, with evidence of apical and mid–distal interventricular septum hypokinesia of the left ventricle (EF 40%) and dilated right ventricle (BD 4.8 cm; MD 4 cm) with severely reduced systolic function (TAPSE 10 mm, S RV 7 m/s, FAC, 20%), and severe tricuspid regurgitation. Urgent computed tomography pulmonary angiography (CTPA) excluded pulmonary embolism. Additionally, there was a new troponin increase (5000 ng/ml) and elevated hepatic biomarkers. The clinical picture raised suspicion of myocarditis related to immune checkpoint inhibitor therapy. Corticosteroid therapy was initiated with a daily administration of methylprednisolone 1000 mg. Diagnostic confirmation was sought through autoimmune panel and viral marker assessments, which yielded negative results. Endomyocardial biopsy (EMB) revealed CD4 and CD8–positive lymphocytic infiltration and myocardial necrosis. Despite initial clinical improvement, an arrhythmic storm developed. Despite treatment with a defibrillator, intravenous antiarrhythmic therapy (beta–blocker, amiodarone, and lidocaine), and sedation, the patient unfortunately succumbed. Immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of many solid tumors. However, the dysregulation of immune mechanisms can rarely (2%) lead to autoimmune events involving multiple organs. Myocarditis, despite optimal treatment, is characterized by a mortality rate exceeding 50%, representing a significant challenge in the Intensive Care Unit.
DILATED CARDIOMYOPATHY, GUIDELINES PERSONALIZATION OF CARE
Authors: Spinelli A , Macchiusi A , Marino G , Di Fusco S , Pignalberi C , Colivicchi F
Published: May 2024

The term Dilated cardiomyopathy (CMD) refers to a family of diseases characterized by complex interactions between environment and genetic predisposition. Diagnostic tools as cardiac magnetic resonance imaging (MRI) must be systematically implemented in clinical practice to define the etiological cause and undertake a specific therapeutic treatment. We present the case of a young man with CMD and severe left ventricular dysfunction (ejection fraction, EF: 14%; left ventricular end–diastolic volume (LVEDV): 251 ml/m2; left ventricular end–systolic volume (LVESV): 197 ml/m2. The patient has a family history of sudden cardiac death (SCD). He is affected by a psychiatric pathology (ADHD) and has a history of alcohol and drug addiction. Many diagnostic hypotheses have been considered for etiological research (viral myocarditis, genetic or alcoholic–induced cardiomyopathy, toxic substances such as narcotics and psychiatric drug–induced cardiomyopathy). MRI after 11 days in hospital confirmed FE 14%, LVEDV: 320 ml/m2, LVESV: 275 ml/m2; reduction of the wall thickness at the antero–septal wall to the middle tract; areas of altered signal, hyperintense in T2W sequences, at the left ventricular myocardial wall suspected of myocardial edema, associated with extended signal hyperintensity of periventricular tissue, which show marked enhancement immediately after intravenous contrast agent administration (Fig. 1). The underlying psychiatric pathology and the possibility of poor adherence to the maintenance of the wearable defibrillator did not facilitate the clinical follow–up which should have included the identification of the etiological cause and the appropriate treatment guaranteeing the temporary prevention of SCD. So, it was decided to make a personalized therapeutic choice, the patient underwent implantation of a subcutaneous defibrillator, pending a better diagnostic definition and the possible need of other therapies as cardiac transplantation/implantation of mechanical assistance device.
ENTRECTINIB–INDUCED ACUTE RIGHT HEART FAILURE IN A PATIENT WITH METASTATIC LUNG ADENOCARCINOMA
Authors: Saaidi S , Bertolini R , Piroli F , Manca F , Cioni E , Tarantini L , Navazio A
Published: May 2024

We report a case report of a 45–year–old woman with a recent diagnosis of stage IV lung adenocarcinoma (PDL1 60%) with brain metastases, who started entrectinib 600 mg orally once daily. Four days after entrectinib initiation, the patient activated the emergency medical services for acute onset of marked fatigue and hypotension. The ECG performed by the emergency unit showed a marked ST–segment elevation in the infero–lateral leads. Therefore, emergent coronary angiography was performed and no evidence of coronary disease was reported. Subsequently, the patient was admitted to the Coronary Care Unit. Clinical evaluation revealed labile hemodynamics, as the patient presented mental confusion, persistent hypotension (BP 90/50 mmHg) and bradycardia (HR 30 bpm). Laboratory testing showed elevated NT–pro BNP, troponin I and transaminases, normal CRP. The electrocardiogram showed persistent diffuse ST–segment elevation. Transthoracic echocardiogram showed severe dilatation and hypokinesia of the right ventricular (GLS VDx –4.5%), with diastolic “D–shape”, normal left ventricular ejection fraction, no significant valvular disease, circumferential pericardial effusion. Clinical, laboratory and instrumental findings suggested a condition of acute right heart failure. We performed urgent computed tomography pulmonary angiography (CTPA) which resulted negative for acute pulmonary embolism. Hence, supportive therapy with dobutamine, norepinephrine and fluid resuscitation was started, with subsequent hemodynamic stabilization. Since no other etiology was demonstrated by the extensive testing, we attributed the acute right ventricular dysfunction to the recent introduction of entrectinib therapy. Therefore, the drug was discontinued. During the hospitalization we observed a rapid normalization of electrocardiogram and right ventricle function by transthoracic echocardiogram, accompanied by a progressive improvement of laboratory parameters. In order to better define right ventricle function and dimension, the patient underwent cardiac magnetic resonance imaging which showed a normal right ventricle ejection fraction (RV EF 52%), the absence of myocardial edema or late gadolinium enhancement and normal volume of the right ventricle. After six days of hospitalization the patient was discharged. Our case report adds to the limited available literature of cardiac toxicity of entrectinib.
CARDIOVASCULAR TOXICITY IN METASTATIC PROSTATE CANCER TREATMENT: BALANCING RISKS, TREATING CONSEQUENCES
Authors: Livrieri A , Massari F , Scicchitano P , De Feo D , Pinto M , Abruzzese S , Tangorra M , Trotta F , Cannito A , Caldarola P , Potenza A
Published: May 2024

Introduction

Enzalutamide inhibits the receptor of androgen hormones. It is administered for treating metastasized prostate cancer. Enzalutamide is known to have a cardiotoxic effect.

Case Report

A 76 year–old man on–treatment for hypertension and overall good health underwent radical prostatectomy and bilateral ileo–obturator lymphadenectomy in 2021 for prostate cancer. In July 2023, infiltrated lymph node and lung/bone metastases were identified. Therefore, oncologist started Enzalutamide administration, i.e. Androgen Deprivation Therapy. Ecocardiography before therapy showed no alterations in cardiac morphology with normal left ventricle ejection fraction (LVEF). Three months after Enzalutamide administration, he experienced worsening dyspnea and peripheral lower extremity edema. He was admitted to the emergency Department of our hospital due to worsening dyspnea at rest, diffuse crackles and increased values in brain natriuretic peptide (BNP, 3203 pg/mL) and troponins. He was transferred to Intensive Care Unit for acute heart failure. Instrumental findings: 2D ECHOCARDIOGRAPHY: LVEF ∼20%, marked global hypocontractility at strain evaluation (GLS –9.3%); LUNG ULTRASOUND: abundant bilateral basal pleural effusion on the right extending to the middle field with atelectasis of the contiguous parenchyma; 24h Holter ECG: frequent supraventricular and ventricular ectopic arrhythmias. He begins non–invasive ventilation (NIV), high–dose diuretics, and Levosimendan. We observed amelioration in symptoms, reduction in pleural effusion, peripheral edema, and BNP levels (from 3203 pg/ml to 468.6 pg/ml). We proceed with weaning from NIV by monitoring respiratory function and performance by means of blood gas analysis. Amelioration in congestion status was evaluated by bioimpedance. After clinical stabilization, coronary angiography was performed which highlighted a bi–vessel obstructive coronary artery disease (long critical stenosis, ∼80%, on the proximal–middle section of the left anterior descending artery, ∼70% at middle section of circumflex and proximal section of first margianl). Therefore, revascularization by PCI plus DES was performed on proximal–middle LAD and on CX–MO1. Patient was discharged soon after in stable condition and underwent outpatient follow–up.

Conclusions

Enzalutamide might provoke important cardiotoxic effects. It might induce acute cardiac impairment and/or coronary artery diseases. Further analysis and evaluations should be performed.
SEPTAL COLLATERAL PERFORATION COMPLICATED BY INTRAVENTRICULAR SEPTAL HEMATOMA: RESOLUTION BY COIL EMBOLIZATION
Authors: Minghini A
Published: May 2024

A 76–year–old man with effort angina was admitted to our cardiology department for an elective coronary angiography (CA). Diagnostic CA revealed severely calcified three–vessel coronary artery disease (CAD) with chronic total occlusions (CTO) of the right dominant coronary artery (RCA) and left circumflex artery (LCX), and severe calcific stenosis of the left descending artery (LAD). An urgent percutaneous coronary intervention (PCI) to treat the LAD was carried out because of ECG modifications and chest pain immediately after CA. During the procedure a septal collateral perforation occurred leading to abrupt development of a large intraventricular septal hematoma (IVSH). Urgent embolization of the culprit vessel with coils was performed using block and deliver (BAD) technique. Rapid hematoma expansion involved another proximal septal collateral. A prompt second coil embolization was carried out arresting the growth of the septal hematoma. The patient was discharged in stable condition and complete resolution of IVSH was confirmed by transthoracic echocardiogram two months later. Timely management of the septal perforation and close echocardiographic monitoring resulted in complete hematoma resolution and a satisfactory outcome.
A CASE OF ARRHYTHMIC MITRAL VALVE PROLAPSE
Authors: Rocchi F , Lorenzini B , Sciarra L
Published: May 2024

Mitral valve prolapse (MVP) is a common valvular abnormality and the natural history of MVP is generally benign. However, MVP has been associated with an increased risk for arrhythmic sudden cardiac death (SCD). Moreover, ventricular and supraventricular arrhythmias are common in patients with MVP. Therefore, risk stratification for SCD is particularly challenging in patients diagnosed with MVP. There are several marker that may be associated with heightened risk of SCD including family history of SCD, T–wave inversion in the inferior leads on the 12–lead ECG, ventricular arrhythmias on ambulatory ECG, echocardiographic measures such as several mitral regurgitation, leaflet redundancy, mitral anular disjunction (MAD), left ventricular systolic dysfunction as well as myocardial fibrosis in the left ventricular inferolateral basal region and papillary muscles detected by magnetic resonance imaging. It is important to identify patients at high arrhythmic risk to implement appropriate primary prevention strategy of SCD. We report the asymptomatic patient with MVP and higher risk of SCD.A 48 years–old man was asymptomatic and with no relevant personal and family history. He finded frequent ventricular ectopic beats, with LBBB and DBBB morphology and superior axis at exercise stress test during screening for competitive sport eligibility. The previous transthoracic echocardiogram showed the mitral valve with a myxomatous appearance and prolapse of both leaflets, as well as MAD and preserved biventricular systolic function.The electrocardiogram (ECG) showed sinus rhythm with non–specific ventricular repolarization alterations. Coronary computed tomography angiography excluded coronary disease. The 24–hour Holter ECG revealed very frequent premature ventricular contractions (PVCs), 17% of all beats, polymorphic with LBBB or DBBB morphology and superior axis, in bigeminy and trigeminy, with frequent doublets and triplets. The patient was referred for cardiac magnetic resonance imaging (CMRI), which revealed basal inferior–lateral fibrosis by late gadolinium enhancement, mitral valve prolapse and mitral anular disjunction, with a distance of 15 mm.The patient is diagnosed MPV at high arrhythmic risk. Was initiated medical therapy with beta–blockers, frequent monitoring and abstention from intense–moderate physical activity.
IF YOU WANT TO GO FAST, GO ALONE. IF YOU WANT TO GO FAR, ABLATE AF: A CASE REPORT
Authors: Piscione M , Dajana P , Crispino E , Frau L , Halasz G , Ussi G , Grigioni F , Gabrielli D
Published: May 2024

We report a case of a 70–years–old woman who was admitted at the Emergency Department of our hospital with chest discomfort, palpitations and dyspnoea at rest. Her cardiovascular risk factors were: arterial systemic hypertension and atrial fibrillation. She had been diagnosed with Fabry disease about twenty years before and she had undergone bilateral septal myectomy to alleviate left ventricular outflow tract obstruction. She had been previously implanted with a pacemaker and her last left ventricular ejection fraction was of 50%. The patient had associated symptoms and signs, including monolateral mild hearing loss, neuropathic pain in treatment with corticosteroids and verticillate cornea. At the entrance in CICU, the EKG showed: atrial fibrillation at 160 bpm, left ventricular hypertrophy by t voltage criteria with secondary repolarization abnormalities. PA=90/45 mmHg, SpO2=85% in room air. The transthoracic echocardiogram demonstrated a reduced left ventricular ejection fraction (EF=35%) with increased filling pressure. A chest tomography showed multiple heterogeneous parenchymal consolidations, suggestive of active bronchopneumonic foci, which were treated with antibiotics. A transesophageal echocardiogram demonstrated Windsock–like appearance of the auricle, with the detection of stratified thrombus and microcalcification. The rhythm was unsuccessfully controlled with Esmolole c.i., Verapamil c.i. and Metoprolole with bolus injection and intravenous administration. It was started Noradrenaline and Furosemide infusion. Because of low pressure values and high inflammatory markers, low dose of Dobutamine was initiated but the patient developed ventricular fibrillation which was successfully shocked. After that, she was urgently transferred in Intensive Care Unit. After three days, she returned to CICU with Landiolol c.i.. and inotropes. She was gradually weaned off inotropes and the inflammatory markers got improved but the heart rate was not under control. After the test with Adenosine, it was decided to ablate the atrioventricular node with relief of signs and symptoms.

Conclusions

Fabry disease is a X–linked recessive lysosomal storage disorder. In our case, it is demonstrated that the increase in the heart rate allows to maintain the cardiac output so it is considered a measure of compensation of hypotension and septic vasodilation. However, once the pneumonia is resolved, it is possible to ablate and pace since medical therapy is not effective.
AN ISOLATED ACUTE RIGHT VENTRICULAR INFARCTION
Authors: Cortese F , Costantino M , Clemente M , Stolfi L , Di Marino S , Luzi G
Published: May 2024

Isolated right ventricular infarction occurs only in about 3% of the overall myocardial ischemic episodes. Clinical presentation is often insidious and variable case by case. The correct diagnosis is therefore crucial for a proper management, and a good prognosis in the short and long term. A 72–year–old patient suffering from arterial hypertension went to the emergency room of our hospital for malaise and asthenia for about 12 hours that have increased in 3–4 hours before the arrival. He was sweating, tachypneic with normal value of the oxygen saturation to the finger (SpO2:96%), with arterial hypotension (pressure values = 85/50 mmHg), turgor of the jugular veins in the absence of peripheral edema. Cardiac examination revealed no pathological noises and lung examination revealed clear lung fields. Electrocardiogram showed sinus tachycardia at a rate of 118 bpm, second degree atrioventricular (AV) block 2:1 type and an AV conduction delay with a first–degree AV block (P–Q interval: 320–330 msec). A pulmonary P wave was present and the QRS complex showed predominant R waves in V2–V3 with slight repolarization abnormalities (figure, panel A). An ST–elevation in right precordial leads, V3R and V4R was evident. (figure, panel B). Echocardiographic evaluation showed a hypertrophic left ventricle with normal volume and function, with marked enlarged right sections (figure, panels C–H). Moreover, we can observe the flattening of the interventricular septum with a D shaped left ventricle. Septal flattening occurred only in diastole, expression of RV volume overload (figure, panels F–H). After taking 180 mg of ticagrelor administrated orally and 150 mg of aspirin intravenously, the patient was immediately transferred to the catheterization laboratory for emergency coronary angiography. Coronary angiography highlighting an ostial thrombotic obstruction of a co–dominant right coronary artery (RCA) in the absence of significant stenosis of the left coronary circulation (figure, panels I–M). Primary percutaneous coronary intervention of RCA was performed with STENT implantation with a good postoperative result. (figure, panels L). During the hospital stay, the patient showed a good clinical status without any CV events, with progressively normalization of electrocardiographic abnormalities and persistent sinus rhythm. He was discharged after ten days.
NAPHAZOLINE ABUSE: A RARE CASE OF MINOCA
Authors: Galasso M
Published: May 2024

Nasal vasoconstrictors are some of the most widely used over–the–counter drugs, considered by many consumers as relatively safe with few significant side effects. At recommended dosage, the drug produces local vasoconstriction in nasal mucous membranes. However, the use of such drugs has been linked to cardiovascular adverse effects, including hypertension, arrhythmias, prolongation of the QT interval, and angina pectoris. The various cardiovascular adverse effects may occur with both oral and nasal administration and after a single dose or prolonged treatment, without dose–effect and independently of vascular status and age. While the effects of ephedrine and pseudoephedrine have been widely studied, the effects of naphazoline are less well known. We describe the case of a previously healthy man who experienced a MINOCA (myocardial infarction with non–obstructive coronary arteries) after abuse of recommended dose of Naphazoline. To our knowledge, this is the first time that a strict temporal relation between the occurrence of MINOCA and topical naphazoline abuse is being described.
A COMPLEX POST CARDIAC–ARREST SYNDROME: FROM UNCERTAIN NEUROLOGICAL OUTCOME TO HEMORRHAGIC COMPLICATION
Authors: Vitale E , Sorini Dini C , Cesareo F , Righini F , Ceschia N , Valente S
Published: May 2024

A 49–years–old woman with type II diabetes mellitus, hypothyroidism and Churg–Strauss syndrome experienced chest pain with loss of consciousness. Emergency service was called and CPR promptly started. Cardiac arrest with shockable rhythm was documented, DC–shock performed with sign of anterior STEMI after ROSC, then refractory cardiac arrest appeared. The patient was centralized in our hospital and VA–ECMO was positioned through a percutaneous femoral access in cath–lab. Coronary angiography showed acute occlusion of the mid–proximal LAD and subocclusive stenosis of the dominant Cx for which PCI with DES was performed, then intra–aortic balloon pump (IABP) was implanted. At ICCU admission the patient was supported by ECMO and IABP with MAP 65 mmHg and lactates 3.5 mmol/L. Echocardiography and chest X–ray showed severe biventricular dysfunction and pulmonary overload (Fig 1). She was ventilated via ECMO circuit and mechanical ventilation setting protective TV values of 6 ml/kg. Diuresis was good with low dose of furosemide, lactates progressively decreased. Temperature control was set within 36°C with the cooling system of the ECMO circuit. Cardioaspirin, ticagrelor and bivalirudin were administered. At early neurological stratification EEG documented absence of epileptiform anomalies, responsiveness to painful stimuli, SSPE showed normal and symmetrical morphology, NSE at 48 h was 59 ng/mL, she opened eyes and performed simple orders. Levosimendan was administered with partial recovery of the right ventricular dysfunction leading to ECMO removal on 5th day. Due to poor consciousness recovery despite sedation reduction, percutaneous tracheostomy was performed on 8th day, IABP removed and the following day all vasopressors suspended. Neurological improvement allowed transition to spontaneous breathing and weaning from mechanical ventilation; on 19th day tracheostomy was removed. Massive enterorrhagia appeared after ECMO removal (figure 2). The colonoscopy showed ischemic pancolitis, therefore ticagrelor was suspended. On 18th day clopidogrel was reintroduced based on hemoglobin stability and endoscopic improvement. She was discharged from the cardiology department after a total length of stay of thirty days, with normal neurological status, no motor deficits, recovery of left and right ventricular function, stable hemoglobin levels.
CONCOMITANT ACUTE CORONARY SYNDROME AND PEPTIC ULCER PERFORATION. A DRAMATIC LIFE–THREATING COMBINATION STILL UNRESOLVED
Authors: Schettino M , Bezante G , Porto I
Published: May 2024

Acute myocardial infarction with ST–segment elevation (STEMI) and ulcer peptic perforation are two different conditions that could manifest at the same time. We reported a 79–year–old Caucasian man with hypertension, dyslipidemia and CAD (previous stenting on RCA and LAD) with chest pain, vomiting and tarry stool, with normal vital signs. ECG: ST–segment elevation in inferior leads. Hemoglobin: 7.4 g/dl. TnI: negative. The Chest X–ray was normal. The coronary angiography showed a multivessel disease with a sub–occlusion of RCA, a restenosis borderline of LAD and a critical stenosis of OM. Multiple dilatations on culprit lesion with balloon were performed. There was a regression of the ST–segment elevation in the inferior leads, so the interventional cardiologist decided not to stent the vessel. After PCI, clopidogrel loading dose 600 mg was prescribed and two blood transfusions were administered. The echocardiography showed a mildly reduced ejection fraction with abnormalities of inferior, posterior and lateral walls. Subsequently, the patient was stable, asymptomatic with normal vital signs but, progressively, the blood pressure dropped, and the patient became tachypnoic. The echocardiogram showed micro–bubbles moving in all the left and right cardiac chambers. Chest X–ray showed subdiaphragmatic free air and CT demonstrated free intraperitoneal air and air inside the systemic and portal venous circulation, suggesting a perforated viscus. The patient was transferred directly to the operating room in unstable hemodynamic condition, and there for the first time he complained abdominal pain. During surgery the perforation was found in the first segment of the posterior region of duodenal tract and, because of unstable clinical conditions, a conservative treatment was made with a Petzer sound’s application and a plastic of the perforation with stitches and omentoplasty. The patient passed away three days later because of sepsis. The concomitant presence of STEMI and peptic ulcer perforation is rare, but possible event. In our case it might have been reasonable not to give the DAPT or to halve the loading dose, but this has not been supported by clinical studies. There are no clear guidelines or algorithms to choose what to treat first, and up to now the patient’s management depends on the clinical presentation and the algorithms used in clinical practice are those defined by the 112 staff together with the Emergency Department teams.
ECHOCARDIOGRAPHIC PREDICTORS OF RESIDUAL MR ≥ 2+ AND CLINICAL OUTCOMES ONE YEAR AFTER MITRACLIP IMPLANTATION
Authors: Costantino M , Stolfi L , D‘Addeo G , Cortese F , Fiorilli R
Published: May 2024

Introduction

The extent of residual mitral regurgitation (MR) (1+ vs ≥ 2+) has a notable impact on the outcome of MitraClip (MC) repair of significant functional MR.

Aim

The aim of the study was to analyze the one–year results in our series of patients with functional MR treated with MC.

Materials and Methods

Between 2020 and 2022, 58 consecutive patients underwent percutaneous mitral valve repair with MC technology. All patients had moderate–severe MR on a functional basis.

Results

At one year 10 patients died (mortality 17.2%). The remaining 48 patients had complete follow–up for up to one year and were included in the statistical analysis: The incidence of new hospitalizations was 8.3%; The incidence of grade 1+ and ≥ 2+ MR was 54.1% (26) and 45.9% (22), respectively; In patients with MR ≥ 2+ the clinical and instrumental outcomes were worse than in patients with MR 1+; Posterior leaflet height and extent of immediate postprocedural MR were independent predictors of MR ≥ 2+. In multivariable analysis, preprocedural posterior leaflet height (PLH) (OR 0.16, p = 0.02) and immediate postprocedural MR degree (IPOMR) (OR 12.4, p = 0.03) were predictive; preprocedural Ejection Fraction (EF) was almost significant (OR 0.87, p = 0.08) (Figure 1).

Conclusions

Percutaneous repair with MC of moderate/severe functional MR has favorable one–year outcomes in terms of mortality and rehospitalizations. The best results are obtained in cases with residual MR 1+. Echocardiographic parameters are independent predictors of residual MR ≥ 2+.
CCT‘S CRYSTAL BALL: PREDICTING CARDIOVASCULAR RISK IN AORTIC VALVE STENOSIS PATIENTS UNDERGOING VALVE REPLACEMENT
Authors: Savo M , Pergola V , Bariani R , De Amicis M , Cozza E , Amato F , Martini M , Sonego P , De Conti G , Rigato L , Mattesi G , Bauce B , Illiceto S , Motta R
Published: May 2024

Background and Aims

Currently, computed tomography cardiac imaging (CTCI) plays a fundamental role in the pre–procedural planning of degenerative–calcific aortic valve stenosis(AS) correction. However, its prognostic role in assessing mortality and major adverse cardiovascular events (MACE) has not been extensively explored. CTCI allows for the evaluation of coronary artery calcification(CAC), mitral annular calcifications (MAC), aortic valve calcifications (CVA), and thoracic aorta calcifications (CAT). The aim of our study was to assess whether the presence and extent of CAC, MAC, CVA, and CAT could influence non–cardiovascular mortality (NCM), cardiovascular mortality (CM), and MACE in patients undergoing valve replacement(VR).

Materials and Methods

We collected retrospectivelly clinical and instrumental data and reviewed CTCI using a semi–quantitative approach. CACs were classified according to the visual 2022 Coronary Artery Disease–Reporting and Data System. MACs were defined following the Guerrero et al. study, CVAs according to the Win Registry and CATs were assessed in the ascending aorta, aortic arch, and descending aorta according to the Vos classification.

Results

244 patients(59% male, mean age 80.1±6.6 years), with 91% undergoing transfemoral VR, were enrolled(2016–2018). CM was significantly higher in patients with hypertension,cerebro/peripheral vascular disease, stage IV–V renal insufficiency and history of atrial fibrillation (p=0.012,p<0.001,p=0.005, p=0.034 and p=0.024, respectively). CM was also more pronounced in patients with STS SCORE≥6.7±5.2 and EuroSCOREII≥ 5.5±5.8(p=0.016 and p=0.037). Extensive CAC(p=0.019), a MAC score>7(p=0.051), moderate and severe AVC (p=0.029 and p=0.053) and TAC>270° in aortic arch(p=0.019) were linked to CM. In multivariate analysis, a high MAC score and the presence of moderate AVC persisted as risk factors for CM. The presence of a MAC score >7(p=0.006) and the extension of descending TAC >1.5 mm (p=0.034) were associated with an increased risk of NCM.The presence of extensive TAC (≥270°) measured in the aortic arch and descending aorta were associated with MACE (p=0.034 and p=0.0504 respectively).

Conclusions

CTCI emerges as a crucial tool for evaluating prognostic risk in patients undergoing VR for AS. This type of evaluation can assist clinicians in pre–procedural planning and patient management, allowing for better identification of high–risk patients and optimization of therapeutic strategies
Current of injury amplitude during left bundle branch area pacing implantation: impact of filter settings, ventricular pacing, and lead type
Authors: Burri Haran , Valiton Valérian , Spadotto Alberto , Herbert Julia , Masson Nicolas
Published: May 2024

Aims

Monitoring current of injury (COI) during left bundle branch area pacing (LBBAP) implantation is useful to evaluate lead depth. Technical aspects for recording COI amplitude have not been well studied. Our aims were to evaluate the impact of high-pass filter settings on electrogram recordings during LBBAP implantation.

Methods and results

Consecutive patients with successful LBBAP implantation had unipolar recordings of COI at final lead position at different high-pass filter settings (0.01–1 Hz) from the tip electrode during sensing and pacing, and from the ring electrode during sensing. Duration of saturation-induced signal loss was also measured at each filter setting. COI amplitudes were compared between lumenless and stylet-driven leads. A total of 156 patients (96 males, aged 81.4 ± 9.6 years) were included. Higher filter settings led to significantly lower COI amplitudes. In 50 patients with COI amplitude < 10 mV, the magnitude of the drop was on average 1–1.5 mV (and up to 4 mV) between 0.05 and 0.5 Hz, meaning that cut-offs may not be used interchangeably. Saturation-induced signal loss was on average 10 s at 0.05 Hz and only 2 s with 0.5 Hz. When pacing was interrupted, the sensed COI amplitude varied (either higher or lower) by up to 4 mV, implying that it is advisable to periodically interrupt pacing to evaluate the sensed COI when reaching levels of ∼10 mV. Lead type did not impact COI amplitude.

Conclusion

High-pass filters have a significant impact on electrogram characteristics at LBBAP implantation, with the 0.5 Hz settings having the most favourable profile.
The use of healthcare services and disabling chronic pain: results from the cross-sectional population-based Andalusian Health Survey
Authors: Cáceres-Matos Rocío , Gil-García Eugenia , Vázquez-Santiago Soledad , Cabrera-León Andrés
Published: May 2024

Background

Several factors seem to be related to the use of healthcare services, and chronic pain (CP) is among these characteristics. The objective is to describe the number of visits to a doctor’s surgery or emergency rooms, and the periods of hospitalization; to identify characteristics associated with frequent healthcare use, including disabling chronic pain (DCP) and non-disabling chronic pain (n-DCP).

Methods

Representative population-based cross-sectional study of 6569 people older than 16 years from southern Spain was collected. The frequency of visits to a doctor’s surgery or emergency rooms and periods of hospitalization were defined as at or above the 90th percentile. Binary logistic regression analyses were conducted separately on women and men to identify characteristics associated with being frequent visitors.

Results

People with DCP are more frequent visitors to a doctor’s surgery and emergency rooms and endure longer periods of hospitalization compared to people with n-DCP and without pain. In logistic regression models, people with DCP are twice as likely to over-visit a doctor’s surgery; to endure longer periods of hospitalization and more visits to an emergency room service. No relationship was found in n-DCP.

Conclusions

Disability seems to modulate a greater use of health services among the population with CP, doubling it when compared to n-DCP and n-CP, both in women and men. Understanding the role of disability in the use of healthcare services for individuals with CP allows for the identification of needs and strategies to optimize resources.
Individuals in Securitization: Explaining US Presidents’ Choice to (De)Securitize North Korea
Authors: Schotthöfer Alexander
Published: May 2024

Securitization and desecuritization demonstrate how threat (de)constructions can lead to conflictual or cooperative foreign policies. However, due to its focus on collectivities, securitization theory cannot tell us why leaders choose either securitization or desecuritization. Understanding this choice is crucial because (de)securitization processes can prescribe possible foreign policy options and thus affect the likelihood of conflict and cooperation. To account for leaders’ choices, I draw on political psychology and demonstrate the utility of my approach through an explanation of two US presidents’ preferences for (de)securitizing North Korea. Using leadership trait and operational code analysis, I show that psychological variables shaped Bill Clinton’s and George W. Bush’s preferences because they affected their threat perception and inclination toward conflictual or cooperative actions. These preferences had substantial consequences: While Clinton’s desecuritization attempt led to improvements in US–North Korean relations, Bush’s effort to resecuritize North Korea effectively reversed this progress.
Illuminating the Cryptococcus neoformans species complex: unveiling intracellular structures with fluorescent-protein-based markers
Authors: Shi Ran , Lin Xiaorong
Published: May 2024

Cryptococcus neoformans is a fungal pathogen of the top critical priority recognized by the World Health Organization. This clinically important fungus also serves as a eukaryotic model organism. A variety of resources have been generated to facilitate investigation of the C. neoformans species complex, including congenic pairs, well-annotated genomes, genetic editing tools, and gene deletion sets. Here, we generated a set of strains with all major organelles fluorescently marked. We tested short organelle-specific targeting sequences and successfully labeled the following organelles by fusing the targeting sequences with a fluorescence protein: the plasma membrane, the nucleus, the peroxisome, and the mitochondrion. We used native cryptococcal Golgi and late endosomal proteins fused with a fluorescent protein to label these two organelles. These fluorescence markers were verified via colocalization using organelle-specific dyes. All the constructs for the fluorescent protein tags were integrated in an intergenic safe haven region. These organelle-marked strains were examined for growth and various phenotypes. We demonstrated that these tagged strains could be employed to track cryptococcal interaction with the host in phagocytosis assays. These strains also allowed us to discover remarkable differences in the dynamics of proteins targeted to different organelles during sexual reproduction. Additionally, we revealed that “dormant” spores transcribed and synthesized their own proteins and trafficked the proteins to the appropriate subcellular compartments, demonstrating that spores are metabolically active. We anticipate that these newly generated fluorescent markers will greatly facilitate further investigation of cryptococcal biology and pathogenesis.
Even low levels of cannibalism can bias population estimates for Pacific hake
Authors: Wassermann Sophia N , Adams Grant D , Haltuch Melissa A , Kaplan Isaac C , Marshall Kristin N , Punt André E
Published: May 2024

By incorporating trophic interactions and temperature-dependent bioenergetics, multi-species models such as CEATTLE (climate-enhanced age-based model with temperature-specific trophic linkages and energetics) are a step towards ecosystem-based stock assessment and management of high-value commercial species such as Pacific hake (Merluccius productus). Hake are generalist predators and previous studies in the California Current Ecosystem have determined that their diet consists of ∼30% cannibalism. We used CEATTLE to include cannibalism in a model of hake population dynamics and re-examined hake diet data to determine the proportion by age that can attributed to cannibalism. The proportion was highly variable, ranging between 0 and 80% of stomach contents by weight. When included in the CEATTLE model, the estimated spawning biomass, total biomass, and recruitment increased by 15, 23, and 58%, on average, relative to the single-species model, due to the estimation of time- and age-varying predation mortality, primarily for age-1 hake. The effects of cannibalism varied over time, with further increases in total biomass and recruitment resulting from the age structure of the population following large cohorts in 1980 and 1984. Results from the cannibalism model could be used to inform the estimation of time- and age-varying mortality in the single-species assessment and as a pathway for including ecosystem information in management through environmental and trophic drivers of variability in mortality.
Predicted range expansion of Prostephanus truncatus (Coleoptera: Bostrichidae) under projected climate change scenarios
Authors: Harman Rachel R , Morrison William R , Ludwick Dalton , Gerken Alison R
Published: May 2024

The larger grain borer (Prostephanus truncatus [Horn] [Coleoptera: Bostrichidae]) is a wood-boring insect native to Central America and adapted to stored maize and cassava. It was accidentally introduced to Tanzania and became a pest across central Africa. Unlike many grain pests, P. truncatus populations can establish and move within forests. Consequently, novel infestations can occur without human influence. The objectives of our study were to (i) develop an updated current suitability projection for P. truncatus, (ii) assess its potential future distribution under different climate change scenarios, and (iii) identify climate variables that best inform the model. We used WALLACE and MaxEnt to predict potential global distribution by incorporating bioclimatic variables and occurrence records. Future models were projected for 2050 and 2070 with Representative Concentration Pathways (RCPs) 2.6 (low change) and 8.5 (high change). Distribution was most limited by high precipitation and cold temperatures. Globally, highly suitable areas (> 75%) primarily occurred along coastal and equatorial regions with novel areas in northern South America, India, southeastern Asia, Indonesia, and the Philippines, totaling 7% under current conditions. Highly suitable areas at RCPs 2.6 and 8.5 are estimated to increase to 12% and 15%, respectively, by 2050 and increase to 19% in 2070 under RCP 8.5. Centroids of highly suitable areas show distribution centers moving more inshore and away from the equator. Notably, the result is a range expansion, not a shift. Results can be used to decrease biosecurity risks through more spatially explicit and timely surveillance programs for targeting the exclusion of this pest.
A game theoretic decision forest for feature selection and classification
Authors: Suciu Mihai-Alexandru , Ioana Lung Rodica
Published: May 2024

Classification and feature selection are two of the most intertwined problems in machine learning. Decision trees (DTs) are straightforward models that address these problems offering also the advantage of explainability. However, solutions that are based on them are either tailored for the problem they solve or their performance is dependent on the split criterion used. A game-theoretic decision forest model is proposed to approach both issues. DTs in the forest use a splitting mechanism based on the Nash equilibrium concept. A feature importance measure is computed after each tree is built. The selection of features for the next trees is based on the information provided by this measure. To make predictions, training data is aggregated from all leaves that contain the data tested, and logistic regression is further used. Numerical experiments illustrate the efficiency of the approach. A real data example that studies country income groups and world development indicators using the proposed approach is presented.
The antitumor effect of extracellular vesicles derived from cytokine-activated CD8+ T cells
Authors: Zhang Lin , Meng Yuan , An Yang , Yang Xuena , Wei Feng , Ren Xiubao
Published: May 2024

Extracellular vesicles (EVs) are nano-sized membrane particles secreted by various cell types that are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells, and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we report the EVs released by cytokine-activated CD8+ T (caCD8) cells and its cytotoxicity against cancer cells. CaCD8 cells can release EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokine cocktail ex vivo. The isolated vesicles have typical EV characteristics, such as an oval shape and a size distribution between 30 and 200 nm, as well as CD81 expression. Notably, caCD8-EVs displayed cytotoxicity against various cancer cells in vitro. Furthermore, mechanism analysis demonstrates that caCD8-EVs not only contain typical cytotoxic proteins (i.e. granzyme B and perforin), but also significantly enrich interferon γ (IFNγ) compared with caCD8 cells. EV-derived IFNγ participates in EV-induced apoptosis in cancer cells. Therefore, our data reveal antitumor effects of EVs secreted from caCD8 cells and the potential role of the EV-derived IFNγ.
PHOSPHATE1-mediated phosphate translocation from roots to shoots regulates floral transition in plants
Authors: Dai Senhuan , Chen Huiying , Shi Yutao , Xiao Xinlong , Xu Lei , Qin Cheng , Zhu Yiyong , Yi Keke , Lei Mingguang , Zeng Houqing
Published: May 2024

Phosphorus nutrition has been known for a long time to influence floral transition in plants, but the underlying mechanism is unclear. Arabidopsis phosphate transporter PHOSPHATE1 (PHO1) plays a critical role in phosphate translocation from roots to shoots, but whether and how it regulates floral transition is unknown. Here, we show that knockout mutation of PHO1 delays flowering under both long- and short-day conditions. The late flowering of pho1 mutants can be partially rescued by Pi supplementation in rosettes or shoot apices. Grafting assay indicates that the late flowering of pho1 mutants is a result of impaired phosphate translocation from roots to shoots. Knockout mutation of SPX1 and SPX2, two negative regulators of the phosphate starvation response, partially rescues the late flowering of pho1 mutants. PHO1 is epistatic to PHO2, a negative regulator of PHO1, in flowering time regulation. Loss of PHO1 represses the expression of some floral activators, including FT encoding florigen, and induces the expression of some floral repressors in shoots. Genetic analyses indicate that at least jasmonic acid signaling is partially responsible for the late flowering of pho1 mutants. In addition, we find that rice PHO1;2, the homolog of PHO1, plays a similar role in floral transition. These results suggest that PHO1 integrates phosphorus nutrition and flowering time, and could be used as a potential target in modulating phosphorus nutrition-mediated flowering time in plants.
asteRIa enables robust interaction modeling between chromatin modifications and epigenetic readers
Authors: Stadler Mara , Lukauskas Saulius , Bartke Till , Müller Christian L
Published: May 2024

Chromatin, the nucleoprotein complex consisting of DNA and histone proteins, plays a crucial role in regulating gene expression by controlling access to DNA. Chromatin modifications are key players in this regulation, as they help to orchestrate DNA transcription, replication, and repair. These modifications recruit epigenetic ‘reader’ proteins, which mediate downstream events. Most modifications occur in distinctive combinations within a nucleosome, suggesting that epigenetic information can be encoded in combinatorial chromatin modifications. A detailed understanding of how multiple modifications cooperate in recruiting such proteins has, however, remained largely elusive. Here, we integrate nucleosome affinity purification data with high-throughput quantitative proteomics and hierarchical interaction modeling to estimate combinatorial effects of chromatin modifications on protein recruitment. This is facilitated by the computational workflow asteRIa which combines hierarchical interaction modeling, stability-based model selection, and replicate-consistency checks for a stable estimation of Robust Interactions among chromatin modifications. asteRIa identifies several epigenetic reader candidates responding to specific interactions between chromatin modifications. For the polycomb protein CBX8, we independently validate our results using genome-wide ChIP-Seq and bisulphite sequencing datasets. We provide the first quantitative framework for identifying cooperative effects of chromatin modifications on protein binding.
KinomeMETA: a web platform for kinome-wide polypharmacology profiling with meta-learning
Authors: Li Zhaojun , Qu Ning , Zhou Jingyi , Sun Jingjing , Ren Qun , Meng Jingyi , Wang Guangchao , Wang Rongyan , Liu Jin , Chen Yijie , Zhang Sulin , Zheng Mingyue , Li Xutong
Published: May 2024

Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/.