Risultati per: AGA: linee guida sulla de-prescrizione degli inibitori della pompa protonica

Circulation, Volume 148, Issue Suppl_1, Page A18288-A18288, November 6, 2023. Hypoplastic Left Heart Syndrome (HLHS) is a complex form of congenital heart disease, characterized by severe underdevelopment of the left ventricle, stenosis or atresia of the mitral and aortic valves, and hypoplasia of the ascending aorta and aortic arch. Despite advances in surgical and palliative strategies leading to improved neonatal survival outcomes, HLHS is still associated with early mortality and long-term morbidity. Elucidation of HLHS etiology is compounded by its complex inheritance mechanism and heterogenous genetic landscape, with studies indicating a multigenic etiology. We performed exome sequencing on a parent-offspring trio in which the proband was affected with HLHS and identified a novelde novomissense variant in the gene,RBFOX2,that was bioinformatically predicted to be pathogenic. RBFOX2 belongs to a family of RNA-binding proteins that is broadly expressed in all tissues and regulates splicing and transcription of many targets, including those involved in heart development. In order to determine the in vivo pathogenicity of theRBFOX2variant, we generated a knock-in mouse model harboring orthologous missense RBFOX2 variant using CRISPR/Cas9 technology.RBFOX2KI/KImice were found to be embryonic lethal. Morphological analysis revealed 100% of homozygous mutants exhibit gross developmental defects. Normal Mendelian ratios are found at E9.5 but homozygous mutants display severe growth retardation from E9.5 to E11.5. Histologic analysis demonstrated underdevelopment of the ventricular chambers starting at E9.5. Overall, these mutant mice, harboring a clinically relevant human HLHS variant inRBFOX2, display highly penetrant hypoplastic hearts with significant growth retardation. The use of this new murine model will pave the way for better cellular and molecular characterization of the deficits in RBFOX2 function that contribute to HLHS.

Circulation, Volume 148, Issue Suppl_1, Page A15872-A15872, November 6, 2023. IntroductionGuideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) includes four medication classes and improves survival. However, uptake and adherence to GDMT remain low. Simulation models to project long-term benefits can inform ongoing trials of GDMT implementation strategies (such as a polypill). As such, we sought to develop and validate a mathematical model of HFrEF and GDMT treatment.MethodsWe developed a state-transition, Markov model to simulate hospitalizations, urgent care visits, and cardiovascular and non-cardiovascular death among patients with HFrEF on 0, 2, 3, and 4 GDMT drugs. Input parameters were derived from trials, epidemiologic cohorts, national surveys, and published literature. External validation compared model-projected all-cause mortality with data from the Seattle-HF model and three major HFrEF trials (eplerenone in EMPHASIS-HF, sacubitril/valsartan in PARADIGM-HF, and dapagliflozin in DAPA-HF). Goodness-of-fit was assessed by root-mean-square-error (RMSE), with RMSE ≤ 5.0 considered to be a good fit.ResultsIn external validation, the model accurately replicated 5-year survival curves from the Seattle-HF model among treatment-naïve patients age 65 years (RMSE 1.9), 75 years (RMSE 1.2), and 85 years (RMSE 1.9). Model projections demonstrated good fit among individuals on various combinations of GDMT, with RMSE 0.6-2.8 across all combinations tested (Figure). For a 65-year-old with HFrEF, our model projected a mean survival of 6.3 years without GDMT, increased by 2.5 years on 2-drug, 3.4 years on 3-drug, and 4.7 years on 4-drug GDMT.ConclusionOur model replicated survival outcomes with GDMT in HFrEF and demonstrated improved survival associated with more classes of GDMT. Future work will project the long-term health and economic impacts of implementation strategies to improve GDMT uptake and adherence, incorporating healthcare costs and quality-of-life measures.

Circulation, Volume 148, Issue Suppl_1, Page A18152-A18152, November 6, 2023. Introduction:Recently, percutaneous ventricular assist device (p-LVAD) has been widely applicable for cardiogenic shock. Clinically significant aortic insufficiency (AI) is contraindication for p-LVAD, nevertheless p-LVAD itself can cause de novo AI (dAI) during the support. However the detail of dAI during p-LVAD support was not fully investigated. The aim of this study was to evaluate the clinical impact of AI during p-LVAD support and also investigate the mechanism and risk factor of dAI.Methods:Seventy-seven consecutive patients who underwent p-LVAD support (average age 66.7 years, Impella CP/2.5 in 65 and 5.5/5.0 in 12 cases) from 2018 to 2022 were retrospectively evaluated. The average support periods was 8.0±6.9 days. dAI was defined as development of AI ≥ moderate during p-LVAD support. Aortic valve pathology was examined using autopsy specimens in eight patients.Results:Three patients had AI ≥ moderate before p-LVAD support and underwent surgical intervention (AVR in 2 and AV repair in 1) during p-LVAD support. dAI was observed in 8 patients (10.3%, moderate in 7 and severe in 1). Moderate dAI in four of these patients improved after cardiac recovery and weaning of p-LVAD support. However, in 3 other patients with dAI ≥ moderate developed hemodynamic instability and deceased due to heart failure. In only a patient, moderate dAI remained after p-LVAD weaning with stable hemodynamics. Progression of AI after p-LVAD removal was not observed in all patients. In-hospital mortality was higher in the patient with dAI (75.0 vs. 47.8%, p=0.14). Pathological evaluation revealed hemorrhagic change at LV side of aortic valve with hemosiderin-laden macrophages in 3 autopsy specimens, which suggested contact of p-LVAD catheter. The univariate analysis identified mild AI before p-LVAD support as independent risk factor for dAI (Odd ratio 5.5, 95%CI 0.074-0.45, p

Circulation, Volume 148, Issue Suppl_1, Page A18979-A18979, November 6, 2023. Introduction:Corrected QT interval (QTc) prolongation is the known side effect of multiple medications especially in antipsychotic and antiarrhythmic family. Patients with either inherited or secondary prolonged QTc should be monitored closely as they can develop life threatening complications like Torsades de-pointes and ventricular fibrillation. Here we present a case of cardiac arrest secondary to dexmedetomidine.Case:A 49-year-old female with history of bipolar disorder was admitted to intensive unit for seizure after intentional ingestion of uncounted amount of diphenhydramine pills. Patient was intubated for airway protection and started on propofol. Her vitals at the time of admission included the pulse rate of 76, blood pressure of 102/49 mmHg. Her urine drug screen was positive for TCA and cannabinoids. Her ECG at the time of admission was significant for prolonged QTC of 600msec that improved to 460msec in the consecutive ECGs after administration of total of 4mg intravenous magnesium. Continuous EEG was negative for seizure and she was weaned off sedation. After awakening, she became agitated, after pushes of benzodiazepines, was eventually started on dexmedetomidine. Twenty minutes after starting low dose dexmedetomidine, patient was noted to be in cardiac arrest. Reviewing telemetry prior to event, revealed the R on T phenomenon and Torsades de pointes that lasted for few seconds with progression into ventricular fibrillation.Discussion:Currently dexmedetomidine is labeled with a low to possible risk of Torsade de pointes and QTC prolongation. Dexmedetomidine induced Torsade de pointes might be explained by bradycardia in patients which causes further prolongation of QT interval. Studies have shown that continuous IV infusion of dexmedetomidine at rate of 0.3 mcg/kg/hour can worsen QTC prolongation.Conclusions:In this case we present a case of VFib arrest secondary to Torsade after twenty minutes of infusion of dexmedetomidine without any sign of bradycardia prior to the event. This carries a significant importance as it shows this drug carries a potential risk of QTc prolongation similar to previous studies. Whether this side effect is dose dependent or not requires further investigation.

Circulation, Volume 148, Issue Suppl_1, Page A11698-A11698, November 6, 2023. Introduction:Endocarditis of the aortic valve has a propensity to create A-V conduction disturbances in up to 10% of cases. Torsades de pointes (TdP) is polymorphic ventricular tachycardia in the setting of prolonged QT interval and bradycardia that is typically preceded by a short-long-short sequence of ventricular activation. We present a case of infective endocarditis with aortic root abscess leading to acute 2:1 A-V conduction and culminating in TdP.Case Summary:A 30-year-old male with history of IV drug use and bioprosthetic aortic valve repair presented with pleuritic chest pain, nausea and vomiting. He was febrile and tachycardic with a systolic murmur at the right upper sternal border. Initial electrocardiogram showed sinus rhythm with no conduction abnormalities.ATransthoracic echocardiography showed a large aortic valve vegetation with an abscess cavity.EBlood cultures grew Streptococcus oralis. Two days later, he developed VT/VF arrest requiring external defibrillation. Preceding ECGs and telemetry showed sinus tachycardia with new left bundle branch block and prolonged QTc.BThis progressed to 2:1 AV blockCwith abrupt transition to relative bradycardia and ventricular ectopy leading to short-long-short ventricular intervals and subsequent TdP.DA temporary pacemaker was placed, and he underwent an aortic root reconstruction with valve replacement.Discussion:While both the etiology of TdP and aortic root abscesses leading to conduction system disease are well described, this case exhibits the real time progression of aortic abscess involvement. The patient presented with a normal QRS morphology. During hospitalization, he developed new LBBB, and the appropriate sinus tachycardia then deteriorated into 2:1 AV conduction leading to relative bradycardia. This abrupt transition with QTc prolongation sets up the nidus for ventricular ectopy (due to early after depolarizations) with salvos of short-long-short sequences causing TdP.

Circulation, Volume 148, Issue Suppl_1, Page A15381-A15381, November 6, 2023. Introduction:Drug-coated balloon (DCB) may be an alternative to stents in the treatment of large native coronary artery disease. However, the complications of acute elastic recoil and coronary dissections confine the practical application of DCB. Little is known about the clinical outcomes of different types of dissection after DCB angioplasty with or without stenting.Aims:This study sought to investigate the clinical outcomes of post-DCB dissection in large de novo coronary artery disease.Methods:This was a retrospective observational study. A consecutive series of patients with large native coronary artery disease (reference diameter ≥ 3.0 mm) who occurred coronary dissections after the treatment of DCB angioplasty were included. These patients were divided into stented groups and non-stented groups depending on whether bail-out stents were employed. Post-angioplasty coronary artery dissections were classified into type A-F. The cumulative incidence of major adverse cardiac events (MACE) was compared between the two groups.Results:Between March 2017 and October 2022, 676 patients with large de novo coronary artery disease developed post-DCB angioplasty dissection, 554 of which treated with DCB only, 122 of which underwent bail-out stent implantation. These dissections were type A (60.5%), B (30.9%), C (6.5%), D (1.9%) and F (0.1%), respectively. During a mean follow-up of 1 year, MACE occurred in 60 patients (9 in the stented group and 51 in the non-stented group; 7.4% vs. 9.2%; p=0.522). For type B dissection, the rate of MACE was similar in the stented group than that in the non-stented group (11.1% vs. 8.2%; p=0.502). For type C dissection, the rate of MACE was numerically higher in the non-stented group than that in the stented group (9.5% vs. 0%; p=0.222).Conclusions:For post-DCB angioplasty dissection in large de-novo coronary artery disease, type B dissection requires no bail-out stent implantation and type C dissection deserves further investigation.

Circulation, Volume 148, Issue Suppl_1, Page A12381-A12381, November 6, 2023. Background:The development of de novo multiple myeloma in a patient with transthyretin amyloid cardiomyopathy (ATTR-CM) is rare and is often associated with poor prognosis. Early and definitive diagnosis is crucial to improve survival.Case:A 63-year-old male was evaluated for heart failure. He had a history of hypertension, sick sinus syndrome status post dual chamber pacemaker, non-sustained ventricular tachycardia requiring ablation in addition to bilateral carpal tunnel syndrome, spontaneous biceps tendon rupture, and lumbar spinal stenosis. Transthoracic echocardiogram showed progressive severe left ventricular hypertrophy with a septal thickness of 2.0cm with a normal left ventricular ejection fraction.Decision-Making:Given his history, an amyloid evaluation was performed. Serum and urine assessment for light chain amyloidosis revealed elevated kappa free light chains with kappa/lambda free light chain ratio of 19.30. Bone marrow biopsy at that time showed normocellular bone marrow with less than 3% plasma cells. An abdominal fat pad biopsy was inconclusive. A cardiac MRI was unobtainable given non-compatible pacemaker leads and a technetium-99m pyrophosphate scintigraphy was deferred given his abnormal light chains. An endomyocardial biopsy was performed and revealed wild-type ATTR deposition by mass spectrometry. Serum genetic test confirmed the absence of TTR gene mutation. The patient was started on Tafamadis. Six months later, he was noted to have progressive elevation in kappa free light chains on serial evaluation and underwent a repeat bone marrow biopsy. This showed plasma cell myeloma with 25-30% marrow cellularity and flow cytometry consistent with kappa light chain multiple myeloma. He was started on Daratumumab, Lenalidomide, and Dexamethasone. This resulted in normalization of his free light chain ratio and morphologic remission on repeat bone marrow biopsy.Conclusion:In patients who are found to have monoclonal gammopathy, an endomyocardial biopsy is crucial to evaluate for amyloid cardiomyopathy. These patients should also be monitored for the progression to multiple myeloma.

Circulation, Volume 148, Issue Suppl_1, Page A18340-A18340, November 6, 2023. Introduction:The diagnosis of the Long COVID multi-organ syndrome is impeded by lack of circulating biomarkers.Hypothesis:We hypothesized, that post-COVID syndrome is associated with circulating protein de-regulation, enabling diagnosis of long COVID syndrome.Methods:Consecutive patients (70% female, 55±8y) with long COVID syndrome (n=70, 64.3% female, 49±6y) and non-diseased, non-vaccinated healthy controls (n=23, 70% female, 55±8y) of the Vienna POSTCOV Registry (EC 1008/2021) were included, and blood samples were collected. Proteomics was performed by using the Olink proteomics technology (Olink Proteomics, Uppsala, Sweden), by using cardiovascular, Immunologic, inflammation and neurologic protein (3×96 protein) panels. Protein-protein interaction network were built by selecting the significantly dysregulated proteins from the 4 panels, and were classified into functional groups.Results:Multiplex protein panel revealed 34 significantly de-regulated proteins as compared to controls. Gene ontology categorized the 29 upregulated proteins into several pathways with significant (false discovery rate

The evolution of axillary surgery for patients with breast cancer represents a model of patient-centered, evidence-based de-escalation of therapy. Starting with the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial, published over 40 years ago, where the principle of axillary dissection mainly as a staging procedure was first enunciated, the trajectory of this operation has steadily progressed in the direction that “less is more.” Following NSABP B-04, the motivation for providing axillary dissection became the joint imperative of accurate nodal staging and local control. This paradigm persisted until the evidence-based replacement of axillary dissection with the far less morbid approach of sentinel node biopsy for pathological staging of the clinically negative axilla. The use of axillary dissection was further eroded by the landmark American College of Surgeons Oncology Group Z0011 trial, which demonstrated that diseased lymph nodes could be left intact without impairing breast cancer outcomes, given effective systemic therapy. Most recently, the 10-year results of the AMAROS trial demonstrated equivalent outcomes in women who received axillary dissection or axillary radiotherapy for limited nodal disease in the axilla, with reduced rates of arm lymphedema.

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The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert commentary on the current landscape of artificial intelligence in the evaluation and management of colorectal polyps.