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BACKGROUND: Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs. OBJECTIVES: The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR. METHODS: We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate. RESULTS: Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355). CONCLUSIONS: The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis.
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Insuficiência da Valva Aórtica , Valva Aórtica , Próteses Valvulares Cardíacas , Desenho de Prótese , Sistema de Registros , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter , Humanos , Insuficiência da Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/mortalidade , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Feminino , Masculino , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Idoso de 80 Anos ou mais , Fatores de Risco , Valva Aórtica/cirurgia , Valva Aórtica/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Substituição da Valva Aórtica Transcateter/instrumentação , Readmissão do Paciente , Recuperação de Função Fisiológica , Europa (Continente) , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , HemodinâmicaRESUMO
Aortic valve stenosis is a disease characterized by thickening and narrowing of the aortic valve (AV), most commonly due to calcification, which leads to left ventricular outflow obstruction called calcific aortic valve disease (CAVD). CAVD presents as a progressive clinical syndrome with cardiorespiratory symptoms, often with rapid deterioration. The modern-day pathophysiology of CAVD involves a complex interplay of genetic factors, chronic inflammation, lipid deposition, and valve calcification, with early CAVD stages resembling atherosclerosis. Various imaging modalities have been used to evaluate CAVD, with a recent trend of using advanced imaging to measure numerous AV parameters, such as peak jet velocity. Significant improvements in mortality have been achieved with transcatheter AV repair, but numerous therapeutics and modalities are being researched to delay the progression of CAVD. This article aims to provide a comprehensive review of CAVD, explore recent developments, and provide insights into future treatments with various novel modalities.
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Non-ST-segment elevation myocardial infarction (NSTEMI) is a leading cause of emergency hospitalization across Europe. This study evaluates the in-hospital and mid-term outcomes of patients who underwent coronary artery bypass graft (CABG) after NSTEMI. A retrospective analysis of all cases who underwent isolated CABG after NSTEMI from September 2017 to September 2022 at our center. Patients were stratified according to in-hospital survival. Patient characteristics, operative details, and procedural complications were compared between those who survived and those who did not. Predictors of in-hospital and mid-term mortality were evaluated using logistic and Cox regression modeling. Kaplan-Meier analysis was used to generate a survival curve for all alive patients at the time of discharge. Among 1,011 patients (median age 64 [56 to 72] years, 852 [84.3%] male), 735 (72.7%) underwent urgent, 239 (23.6%) elective, and 37 (3.7%) emergency CABG. The in-hospital mortality was 1.5% (15/1,011 patients). Those who died were more likely to be New York Heart Association class III/IV, have left ventricular ejection fraction <21%, severe renal impairment, peripheral vascular disease (PVD), or poor mobility. Emergency procedures, preoperative ventilation, inotropic support, and intra-aortic balloon pump (IABP) use were also more prevalent among those who died. Logistic regression modeling revealed new postoperative stroke (odds ratio 22.0, 95% confidence interval 3.6 to 135.5, p = 0.001), preoperative IABP use (11.4; 2.4 to 53.7, p = 0.002), new hemodialysis (9.6; 2.7 to 34.7, p <0.001), PVD (5.6; 1.6 to 20.0, p = 0.008), and poor mobility (odds ratio 4.8, 95% confidence interval 1.3 to 18.2, p = 0.022) as independent predictors of in-hospital mortality. In conclusion, new postoperative stroke, preoperative IABP use, new hemodialysis, PVD, and poor mobility are independent predictors of mortality in patients with NSTEMI who underwent isolated CABG.
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Ponte de Artéria Coronária , Mortalidade Hospitalar , Infarto do Miocárdio sem Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Idoso , Mortalidade Hospitalar/tendências , Pessoa de Meia-Idade , Estudos Retrospectivos , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida/tendências , Fatores de RiscoRESUMO
BACKGROUND: Extracellular volume fraction (ECV) is a marker for myocardial fibrosis and infiltration, can be quantified using cardiac computed tomography (ECVCT), and has prognostic utility in several diseases. This study aims to map out regional differences in ECVCT to obtain greater insights into the pathophysiological mechanisms of ECV expansion and its clinical implications. METHODS: Three prospective cohorts were included: patients with aortic stenosis (AS) and coexisting AS and transthyretin cardiac amyloidosis were referred for a transcatheter aortic valve replacement and had ECG-gated CT angiography and Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy to differentiate between the 2 cohorts. Controls had CT angiography and cardiac magnetic resonance demonstrating no significant coronary artery disease or infarction. Global and regional ECVCT was analyzed, and its association with mortality was assessed for patients with AS. RESULTS: In 199 patients, controls (n=65; 66% male), AS (n=115), and coexisting AS and transthyretin cardiac amyloidosis (n=19) had a global ECVCT of 26.1 (25.0-27.8%) versus 29.1 (27.5-31.1%) versus 37.4 (32.5-46.6%), respectively; P<0.001. Across cohorts, ECVCT was higher at the base (versus apex), the inferoseptum (versus anterolateral wall), and the subendocardium (versus subepicardium); P<0.05 for all. Among patients with AS, epicardial ECVCT, rather than any other regional value or global ECVCT, was the strongest predictor of mortality at a median of 3.9 (max 6.3) years (adjusted hazard ratio, 1.21 [95% CI, 1.08-1.36]; P=0.002). CONCLUSIONS: Regional differences in ECVCT suggest a predilection for fibrosis and amyloid infiltration at the base, subendocardium, inferior wall, and septum more than the anterior and lateral myocardium. ECVCT can predict long-term mortality with the subepicardium demonstrating the strongest discriminatory power. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03029026 and NCT03094143.
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Neuropatias Amiloides Familiares , Estenose da Valva Aórtica , Angiografia por Tomografia Computadorizada , Fibrose , Miocárdio , Humanos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/mortalidade , Masculino , Feminino , Idoso , Estudos Prospectivos , Angiografia por Tomografia Computadorizada/métodos , Idoso de 80 Anos ou mais , Miocárdio/patologia , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/mortalidade , Valor Preditivo dos Testes , Prognóstico , Angiografia Coronária/métodos , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Pessoa de Meia-IdadeRESUMO
The Navitor transcatheter heart valve (THV) is the latest iteration of the Portico self-expanding valve system. Early prospective studies have shown promising outcomes, however, there is a lack of complementary 'real-world' data. This study aimed to assess early safety and efficacy outcomes of the Navitor THV using registry data from 6 high-volume United Kingdom transcatheter aortic valve replacement (TAVR) centers. Demographic, procedural, and in-hospital outcome data were retrieved from 6 United Kingdom centers. The primary safety end point was 30-day mortality. Primary efficacy end points were procedural success, mean aortic gradient, and ≥moderate paravalvular leak. Secondary end points included rates of new permanent pacemaker implantation, stroke, and vascular injury. A total of 574 patients (mean age 83.4 years; 54.5% female) underwent Navitor TAVR between January 2020 and May 2023. The 30-day mortality in this patient cohort was 1.6%. Procedural success was 98.1%, mean echo-derived gradient post-TAVR was 7.7 ± 4.8 mm Hg (95% confidence interval [CI] 7.2 to 8.3, p <0.001) and 5.1% of patients had ≥moderate paravalvular leak (sample proportion estimate [pÌ] = 0.051, 95% CI [0.035, 0.073], p <0.001). New permanent pacemaker implantation to discharge was required in 11% (pÌ = 0.119, 95% CI 0.088 to 0.158, p <0.001), stroke occurred in 1.2% of patients (pÌ = 0.017, 95% CI 0.006 to 0.036, p <0.001) and significant vascular injury in 1.6% (pÌ = 0.014, 95% CI 0.005 to 0.032, p <0.001). In conclusion, early procedural outcomes with Navitor TAVR compare favorably to new-generation THVs. Procedural success was high with a low incidence of complications.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Sistema de Registros , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/métodos , Feminino , Masculino , Reino Unido/epidemiologia , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/cirurgia , Desenho de Prótese , Idoso , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Valva Aórtica/cirurgiaRESUMO
The following is a case of vitreoretinal lymphoma masquerading as central serous chorioretinopathy (CSCR). A 74-year-old man presented with blurred vision in the left eye with unilateral subretinal fluid in the setting of exogenous corticosteroid use, which was diagnosed as CSCR and resolved with corticosteroid cessation. He later experienced a similar self-limited episode in the right eye. Subsequently, he developed bilateral vitritis with yellow-white subretinal pigment epithelial infiltrates. Vitreous biopsy confirmed a diagnosis of large B-cell lymphoma. Vitreoretinal lymphoma can masquerade as a number of ocular pathologies, including CSCR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:467-470.].
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Coriorretinopatia Serosa Central , Angiofluoresceinografia , Neoplasias da Retina , Tomografia de Coerência Óptica , Corpo Vítreo , Humanos , Masculino , Coriorretinopatia Serosa Central/diagnóstico , Idoso , Diagnóstico Diferencial , Neoplasias da Retina/diagnóstico , Corpo Vítreo/patologia , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Linfoma Intraocular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Fundo de OlhoAssuntos
Síndrome Coronariana Aguda , Oclusão Coronária , Eletrocardiografia , Humanos , Oclusão Coronária/diagnóstico , Oclusão Coronária/cirurgia , Angiografia Coronária , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgiaRESUMO
OBJECTIVE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiac disorder caused by deposition of wild type or mutated transthyretin. As ATTR-CM is associated with conduction disease, we sought to determine its prevalence in patients with idiopathic high-degree atrioventricular (AV) block requiring permanent pacemaker (PPM) implantation. METHODS: Consecutive patients aged 70-85 years undergoing PPM implantation for idiopathic high-degree AV block between November 2019 and November 2021 were offered a 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan. Demographics, comorbidities, electrocardiographic and imaging data from the time of device implantation were retrospectively collected. RESULTS: 39 patients (79.5% male, mean (SD) age at device implantation 76.2 (2.9) years) had a DPD scan. 3/39 (7.7%, all male) had a result consistent with ATTR-CM (Perugini grade 2 or 3). Mean (SD) maximum wall thickness of those with a positive DPD scan was 19.0 mm (3.6 mm) vs 11.4 mm (2.7 mm) in those with a negative scan (p=0.06). All patients diagnosed with ATTR-CM had spinal canal stenosis and two had carpal tunnel syndrome. CONCLUSIONS: ATTR-CM should be considered in older patients requiring permanent pacing for high-degree AV block, particularly in the presence of left ventricular hypertrophy, carpal tunnel syndrome or spinal canal stenosis.
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Amiloidose , Bloqueio Atrioventricular , Síndrome do Túnel Carpal , Humanos , Masculino , Idoso , Feminino , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/terapia , Estudos Retrospectivos , Prevalência , Pré-Albumina , Síndrome do Túnel Carpal/complicações , Constrição Patológica/complicaçõesRESUMO
BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16â241 patients with 19â401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.
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Amiloidose , Cardiomiopatias , Humanos , Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Inteligência Artificial , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
Hansen solubility parameters (HSP) of 15 commercially relevant biobased and biodegradable polyesters were experimentally determined by applying a novel approach to the classic solubility study method. In this approach, the extent of swelling in polymer films was determined using a simple equation based on the mass difference between swollen and nonswollen film samples to obtain normalized solvent uptake (N). Using N and HSPiP software, highly accurate HSP values were obtained for all 15 polyesters. Qualitative evaluation of the HSP values was conducted by predicting the miscibility of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHB-co-HHx, 7 mol % HHx) and poly(lactic acid) (PLA) with a novel lignin-based plasticizer (ethyl 3-(4-ethoxy-3-methoxyphenyl)propanoate, EP) with a relative energy difference (RED) less than 0.4. Additionally, an HSP-predicted plasticizer (di(2-ethylhexyl) adipate, DA) with a larger RED (>0.7) was used to demonstrate the effects of less-miscible additives. Plasticized samples were analyzed by differential scanning calorimetry and polarized optical microscopy (POM) to determine the Tg depression, with EP showing linear Tg depression up to 50% plasticizer loading, whereas DA shows minimal Tg depression past 10% loading. Further analysis by POM reveals that the DA phase separates from both polymers at loadings as low as 2.5% (PHB-co-HHx, 7 mol % HHx) and 5% (PLA), while the EP phase separates at a much higher loading of 50% (PHB-co-HHx, 7 mol% HHx) and 30% (PLA).
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In the Targeted therapy with a localised abluminal coated, low-dose sirolimus-eluting, biodegreadable polymer coronary stent (TARGET; NCT02520180) All Comers trial the biodegradable polymer (BP) sirolimus-eluting FIREHAWK stent was noninferior to the durable polymer (DP) everolimus-eluting XIENCE stent with respect to target lesion failure (TLF) at 1 and 5 years; however, the long-term safety and efficacy in the setting of acute coronary syndromes (ACS) are not known. We sought to assess the long-term outcomes in ACS versus chronic coronary syndromes (CCS) with BP sirolimus-eluting stent (SES) versus DP everolimus-eluting stent (EES). The TARGET AC study was a multicenter, open-label, noninferiority trial of all comer patients randomly allocated 1:1 to BP SES or DP EES (stratified by ST-elevation myocardial infarction and study site). In this predefined substudy, the outcomes were compared based on clinical presentation (ACS vs CCS) and treatment allocation. A total of 1,653 patients were enrolled (728 with ACS and 922 with CCS), with 94% completing the 5-year follow-up. The baseline characteristics were well-matched between the 2 stent types; however, co-morbidities were more prevalent in the CCS than in the ACS population. TLF (15.5% vs 17.7%, p = 0.24), patient-oriented outcomes (32.0% vs 34.4%, p = 0.31), and stent thrombosis (4.1% vs 3.3%, p = 0.40) were similar between patients with ACS and patients with CCS. In the ACS cohort, the outcomes at 5 years for BP SES versus DP EES were similar for TLF (16.0% vs 14.9%, p = 0.70), ischemia-driven target lesion revascularization (5.6% vs 8.3%, p = 0.17), and definite/probable stent thrombosis (2.7% vs 4.6%, p = 0.18). The same was true for the CCS cohort, with 5-year outcomes for BP SES versus DP EES for TLF (18.0% vs 17.4%, p = 0.82), ischemia-driven target lesion revascularization (6.4% vs 5.0%, p = 0.37), and definite/probable stent thrombosis (3.0% vs 1.8%, p = 0.26). In conclusion, in the TARGET AC trial, 1 in 3 patients had a major adverse event at 5 years, irrespective of CCS or ACS presentation. Long-term, the BP sirolimus-eluting FIREHAWK stent was as safe and effective as the DP everolimus-eluting XIENCE stent across the spectrum of clinical presentations.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Humanos , Implantes Absorvíveis , Síndrome Coronariana Aguda/cirurgia , Doença da Artéria Coronariana/terapia , Everolimo/farmacologia , Intervenção Coronária Percutânea/efeitos adversos , Polímeros , Desenho de Prótese , Fatores de Risco , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Trombose/etiologia , Resultado do TratamentoRESUMO
Personalized interventions are deemed vital given the intricate characteristics, advancement, inherent genetic composition, and diversity of cardiovascular diseases (CVDs). The appropriate utilization of artificial intelligence (AI) and machine learning (ML) methodologies can yield novel understandings of CVDs, enabling improved personalized treatments through predictive analysis and deep phenotyping. In this study, we proposed and employed a novel approach combining traditional statistics and a nexus of cutting-edge AI/ML techniques to identify significant biomarkers for our predictive engine by analyzing the complete transcriptome of CVD patients. After robust gene expression data pre-processing, we utilized three statistical tests (Pearson correlation, Chi-square test, and ANOVA) to assess the differences in transcriptomic expression and clinical characteristics between healthy individuals and CVD patients. Next, the recursive feature elimination classifier assigned rankings to transcriptomic features based on their relation to the case-control variable. The top ten percent of commonly observed significant biomarkers were evaluated using four unique ML classifiers (Random Forest, Support Vector Machine, Xtreme Gradient Boosting Decision Trees, and k-Nearest Neighbors). After optimizing hyperparameters, the ensembled models, which were implemented using a soft voting classifier, accurately differentiated between patients and healthy individuals. We have uncovered 18 transcriptomic biomarkers that are highly significant in the CVD population that were used to predict disease with up to 96% accuracy. Additionally, we cross-validated our results with clinical records collected from patients in our cohort. The identified biomarkers served as potential indicators for early detection of CVDs. With its successful implementation, our newly developed predictive engine provides a valuable framework for identifying patients with CVDs based on their biomarker profiles.
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Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Medicina de Precisão , Aprendizado de Máquina , BiomarcadoresRESUMO
Purpose: To present a patient with cystoid macular edema (CME) associated with ponesimod use and offer suggestions for the management of this condition. Methods: A case report is presented. Results: A 75-year-old woman with relapsing-remitting multiple sclerosis had an unremarkable baseline ophthalmic examination prior to starting ponesimod. At her 9-month follow-up, an examination showed the development of CME in the left eye. The patient's macular edema fully resolved after transitioning off ponesimod to an alternative systemic medication and starting treatment with a topical corticosteroid and nonsteroidal anti-inflammatory drug. Conclusions: To our knowledge, this is the first case report discussing the entity and management of ponesimod-associated macular edema. Ponesimod cessation and concomitant topical therapy can result in successful resolution of macular edema.
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AIMS: Surgical ablation of atrial fibrillation (AF) has been demonstrated to be a safe procedure conducted concomitantly alongside cardiac surgery. However, there are conflicting guideline recommendations surrounding indications for surgical ablation. We conducted a systematic review of current recommendations on concomitant surgical AF ablation. METHODS AND RESULTS: We identified publications from MEDLINE and EMBASE between January 2011 and December 2022 and additionally searched Guideline libraries and websites of relevant organizations in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 895 studies screened, 4 were rigorously developed (AGREE-II > 50%) and included. All guidelines agreed on the definitions of paroxysmal, persistent, and longstanding AF based on duration and refraction to current treatment modalities. In the Australia-New Zealand (CSANZ) and European (EACTS) guidelines, opportunistic screening for patients >65 years is recommended. The EACTS recommends systematic screening for those aged >75 or at high stroke risk (Class IIa, Level B). However, this was not recommended by American Heart Association or Society of Thoracic Surgeons guidelines. All guidelines identified surgical AF ablation during concomitant cardiac surgery as safe and recommended for consideration by a Heart Team with notable variation in recommendation strength and the specific indication (three guidelines fail to specify any indication for surgery). Only the STS recommended left atrial appendage occlusion (LAAO) alongside surgical ablation (Class IIa, Level C). CONCLUSION: Disagreements exist in recommendations for specific indications for concomitant AF ablation and LAAO, with the decision subject to Heart Team assessment. Further evidence is needed to develop recommendations for specific indications for concomitant AF procedures and guidelines need to be made congruent.
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Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Acidente Vascular Cerebral , Cirurgia Torácica , Estados Unidos , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , AustráliaRESUMO
OBJECTIVES: Grading the severity of moderate mixed aortic stenosis and regurgitation (MAVD) is challenging and the disease poorly understood. Identifying markers of haemodynamic severity will improve risk stratification and potentially guide timely treatment. This study aims to identify prognostic haemodynamic markers in patients with moderate MAVD. METHODS: Moderate MAVD was defined as coexisting moderate aortic stenosis (aortic valve area (AVA) 1.0-1.5 cm2) and moderate aortic regurgitation (vena contracta (VC) 0.3-0.6 cm). Consecutive patients diagnosed between 2015 and 2019 were included from a multicentre registry. The primary composite outcome of death or heart failure hospitalisation was evaluated among these patients. Demographics, comorbidities, echocardiography and treatment data were assessed for their prognostic significance. RESULTS: 207 patients with moderate MAVD were included, aged 78 (66-84) years, 56% male sex, AVA 1.2 (1.1-1.4) cm2 and VC 0.4 (0.4-0.5) cm. Over a follow-up of 3.5 (2.5-4.7) years, the composite outcome was met in 89 patients (43%). Univariable associations with the primary outcome included older age, previous myocardial infarction, previous cerebrovascular event, atrial fibrillation, New York Heart Association >2, worse renal function, tricuspid regurgitation ≥2 and mitral regurgitation ≥2. Markers of biventricular systolic function, cardiac remodelling and transaortic valve haemodynamics demonstrated an inverse association with the primary composite outcome. In multivariable analysis, peak aortic jet velocity (Vmax) was independently and inversely associated with the composite outcome (HR: 0.63, 95% CI 0.43 to 0.93; p=0.021) in an adjusted model along with age (HR: 1.05, 95% CI 1.03 to 1.08; p<0.001), creatinine (HR: 1.002, 95% CI 1.001 to 1.003; p=0.005), previous cerebrovascular event (85% vs 42%; HR: 3.04, 95% CI 1.54 to 5.99; p=0.001) and left ventricular ejection fraction (LVEF) (HR: 0.97, 95% CI 0.95 to 0.99; p=0.007). Patients with Vmax ≤2.8 m/s and LVEF ≤50% (n=27) had the worst outcome compared with the rest of the population (72% vs 41%; HR: 3.87, 95% CI 2.20 to 6.80; p<0.001). CONCLUSIONS: Patients with truly moderate MAVD have a high incidence of death and heart failure hospitalisation (43% at 3.5 (2.5-4.7) years). Within this group, a high-risk group characterised by disproportionately low aortic Vmax (≤2.8 m/s) and adverse remodelling (LVEF ≤50%) have the worst outcomes.
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Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/mortalidade , Insuficiência da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/mortalidade , Hemodinâmica , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de RiscoRESUMO
INTRODUCTION: The incorporation of a three-dimensional (3D) framework enables the surgeon to strategically plan their surgical intervention through the utilisation of the printed model. This encompasses the process of ascertaining the surgical approach, choosing the suitable reduction technique, finding the required implant dimensions, defining the ideal placement and alignment of the implant, and conducting a simulated practise of the procedure using a 3D printed duplicate of the anatomical structures. Therefore, we designed this study to evaluate the role of two imaging modalities (computed tomography (CT) and magnetic resonance imaging (MRI)) for pre-surgical planning for orthopaedic surgeries. METHODOLOGY: The present investigation entailed a prospective analysis of total knee arthroplasties (TKAs) that were performed using patient-specific instrumentation (PSI) from 2019 to 2022. After performing the bone resection operation utilising a customised cutting jig specific to each patient, the exact thickness of the resected bone was evaluated using a vernier calliper. In the MRI group, the researchers directly compared the cutting thickness during surgery with the consistency planned before the operation. In contrast, the CT group added the presumed cartilage thickness (2 mm) to the actual thickness of the bone that was removed from the lateral condyles. RESULTS: The planned incision thickness in the distal femoral was 8.5 ± 0.8 in the CT group and 8.9 ± 0.5 in the MRI group, while the actual incision thickness was reported as 9.8 ± 0.54 in CT and 8.3 ± 1.1; however, no significant mean difference was found between both groups. The planned incision thickness was 2.6 ± 1.1 in the CT group and 2.43 ± 1.66 in the MRI group, while the actual thickness was observed as 2.5 ± 0.6 and 2.88 ± 1.12 without significant difference (p = 0.86). CONCLUSION: While magnetic resonance imaging (MRI) allows for the visualisation of cartilage, it has been observed that the MRI-based patient-specific instrumentation (PSI) system does not exhibit superior accuracy in projecting bone incision thickness compared to the computed tomography (CT)-based PSI system.
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Aim: To investigate the limitations of diagnosing glaucoma in patients with coexistent neurodegenerative disease (NDD) by collecting information on demographics, examination findings, optical coherence tomography (OCT), and visual field (VF) tests. Materials and methods: Retrospective cohort study of patients with primary open-angle glaucoma and coexistent dementia, multiple sclerosis (MS), Parkinson's disease (PD), or cerebrovascular accident (CVA) from 2014 to 2020. We included patients with a minimum of 3 years of follow-up. Demographics, ophthalmic exam, OCT, and VF findings were reported and compared across NDD groups using the Chi-squared and analysis of variance tests. Results: We included 199 patients with glaucoma and coexistent NDD, including dementia (51.3%), CVA (11.2%), PD (18.1%), and MS (19.6%). Cupping, neuroretinal rim thinning, pallor, and peripapillary atrophy of the optic nerve were most frequently observed. There was a high number of missing values from OCT to VF tests, and zero patients had a complete OCT or VF test. Additionally, 67.8 and 77.4% of patients received <1 OCT and VF/year, respectively. Retinal nerve fiber layer (RNFL) thinning was observed most frequently in the superior (33.2% OD and 30.7% OS) and inferior (25.6% OD and 30.2% OS) quadrants, with the most significant thinning seen in CVA patients compared to other NDDs (p < 0.05). Glaucoma hemifield tests (GHTs) were abnormal in 23.1% OD and 22.6% OS, and the average mean deviation was -7.43 [standard deviation (SD) 8.23] OD and -8.79 (SD 7.99) OS. Conclusion: The OCT and VF tests are frequently unavailable and may be confounded in patients with coexistent glaucoma and NDDs, complicating glaucoma diagnosis and management. Clinical significance: Diagnosing and managing glaucoma in patients with coexistent NDD is difficult, given the lack of available and reliable OCT and VF testing data. Providers may be forced to rely on intraocular pressure (IOP) and other imperfect measures. How to cite this article: Ciociola EC, Patel K, Blahnik T, et al. A Retrospective Cohort Study on the Difficulties of Diagnosing and Managing Glaucoma in Patients with Coexistent Neurodegenerative Disease. J Curr Glaucoma Pract 2023;17(3):126-133.
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The functional role of CD8+ lymphocytes in tuberculosis remains poorly understood. We depleted innate and/or adaptive CD8+ lymphocytes in macaques and showed that loss of all CD8α+ cells (using anti-CD8α antibody) significantly impaired early control of Mycobacterium tuberculosis (Mtb) infection, leading to increased granulomas, lung inflammation, and bacterial burden. Analysis of barcoded Mtb from infected macaques demonstrated that depletion of all CD8+ lymphocytes allowed increased establishment of Mtb in lungs and dissemination within lungs and to lymph nodes, while depletion of only adaptive CD8+ T cells (with anti-CD8ß antibody) worsened bacterial control in lymph nodes. Flow cytometry and single-cell RNA sequencing revealed polyfunctional cytotoxic CD8+ lymphocytes in control granulomas, while CD8-depleted animals were unexpectedly enriched in CD4 and γδ T cells adopting incomplete cytotoxic signatures. Ligand-receptor analyses identified IL-15 signaling in granulomas as a driver of cytotoxic T cells. These data support that CD8+ lymphocytes are required for early protection against Mtb and suggest polyfunctional cytotoxic responses as a vaccine target.
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Mycobacterium tuberculosis , Tuberculose , Animais , Macaca , Tuberculose/microbiologia , Linfócitos T CD8-Positivos , Granuloma , Linfócitos T CD4-PositivosRESUMO
Aortic regurgitation (AR) is associated with morbidity and premature mortality. Surgical aortic valve replacement is not an option for many patients due to an adverse surgical risk profile, whilst transcatheter aortic valve implantation with most available prostheses has demonstrated suboptimal implantation success and outcomes. The JenaValve Trilogy™ system provides an attractive solution for such patients as it utilizes clips that directly attach onto the native valve leaflets to anchor. Initially designed for transapical delivery, the current transfemoral delivery system is under investigation in the United States and approved for aortic stenosis and regurgitation in Europe. We present an expert review on the technical aspects of the Trilogy system, provide a guide for implantation, discuss the available evidence for the technology and provide illustrative case examples.