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1.
Circulation ; 149(23): e1239-e1311, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38718139

RESUMO

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.


Assuntos
American Heart Association , Cardiologia , Cardiomiopatia Hipertrófica , Humanos , Cardiologia/normas , Cardiomiopatia Hipertrófica/terapia , Cardiomiopatia Hipertrófica/diagnóstico , Gerenciamento Clínico , Estados Unidos
2.
J Nucl Cardiol ; 32: 101811, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244976

RESUMO

BACKGROUND: There is currently little information regarding the usage and comparative predictors of mortality among patients referred for single-photon emission computed tomography (SPECT) versus positron emission tomography (PET) myocardial perfusion imaging (MPI) within multimodality imaging laboratories. METHODS: We compared the clinical characteristics and mortality outcomes among 15,718 patients referred for SPECT-MPI and 6202 patients referred for PET-MPI between 2008 and 2017. RESULTS: Approximately two-thirds of MPI studies were performed using SPECT-MPI. The PET-MPI group was substantially older and included more patients with known coronary artery disease (CAD), hypertension, diabetes, and myocardial ischemia. The annualized mortality rate was also higher in the PET-MPI group, and this difference persisted after propensity matching 3615 SPECT-MPI and 3615 PET-MPI patients to have similar clinical profiles. Among the SPECT-MPI patients, the most potent predictor of mortality was exercise ability and performance, including consideration of patients' mode of stress testing and exercise duration. Among the PET-MPI patients, myocardial flow reserve (MFR) was the most potent predictor of mortality. CONCLUSIONS: In our real-world setting, PET-MPI was more commonly employed among older patients with more cardiac risk factors than SPECT-MPI patients. The most potent predictors of mortality in our SPECT and PET-MPI groups were variables exclusive to each test: exercise ability/capacity for SPECT-MPI patients and MFR for PET-MPI patients.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Doença da Artéria Coronariana/diagnóstico por imagem , Exercício Físico
3.
Vasc Med ; : 1358863X241247537, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708691

RESUMO

BACKGROUND: There is wide variation in stress test utilization before major vascular surgery and adherence to practice guidelines is unclear. We defined rates of stress test compliance at our institution and led a quality improvement initiative to improve compliance with American Heart Association (ACC/AHA) guidelines. METHODS: We implemented a stress testing order set in the electronic medical record at one tertiary hospital. We reviewed all patients who underwent elective, major vascular surgery in the 6 months before (Jan 1, 2022 - Jul 1, 2022) and 6 months after (Aug 1, 2022 - Jan 31, 2023) implementation. We studied stress test guideline compliance, changes in medical or surgical management, and major adverse cardiac events (MACE). RESULTS: Before order set implementation, 37/122 patients (30%) underwent stress testing within the past year (29 specifically ordered preoperatively) with 66% (19/29) guideline compliance. After order set implementation, 50/173 patients (29%) underwent stress testing within the past year (41 specifically ordered preoperatively) with 80% (33/41) guideline compliance. In the pre- and postimplementation cohorts, stress testing led to a cardiovascular medication change or preoperative coronary revascularization in 24% (7/29) and 27% (11/41) of patients, and a staged surgery or less invasive anesthetic strategy in 14% (4/29) and 4.9% (2/41) of patients, respectively. All unindicated stress tests were surgeon-ordered and none led to a change in management. There was no change in MACE after order set implementation. CONCLUSIONS: Electronic medical record-based guidance of perioperative stress testing led to a slight decrease in overall stress testing and an increase in guideline-compliant testing. Our study highlights a need for improved preoperative cardiovascular risk assessment prior to major vascular surgery, which may eliminate unnecessary testing and more effectively guide perioperative decision-making.

4.
Curr Cardiol Rep ; 26(6): 497-503, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38722493

RESUMO

PURPOSE OF REVIEW: This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). RECENT FINDINGS: The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.


Assuntos
Doença da Artéria Coronariana , Teste de Esforço , Intervenção Coronária Percutânea , Padrão de Cuidado , Humanos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Análise Custo-Benefício , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco
5.
Phytochem Anal ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103248

RESUMO

OBJECTIVE: Cannabis sativa L. is renowned for its medicinal and recreational uses. With the increasing global legalization of C. sativa L.-based products for medicinal purposes, there is a growing need for well-characterized products. While the stability of cannabinoids such as tetrahydrocannabinol and cannabidiol is well understood, information on the chemical and enantiomeric stability of terpenes remains scarce. This is despite the fact that terpenes are also thought to have pharmacological activity and may contribute to the overall effect of C. sativa L. METHODS: To address these challenges, four analytical methods based on chiral, polar, and apolar gas chromatographic separation combined with either MS or FID detection were developed and validated. These methods successfully separated and quantified a total of 29 terpenes, including 13 enantiomers and 5 diastereomers specific to C. sativa L. Furthermore, terpenes and authentic C. sativa L. flowers and extracts were subjected to UV and heat treatments to observe potential degradation reactions over time. RESULTS: Each terpene generates a unique pattern of degradation products resulting in a diverse array of oxidation and cyclization products. P-cymene was identified as a major product of terpene aging. Notably, no enantiomeric conversion was detected, suggesting that the formation of (-)-α-pinene in cannabis extracts, for example, originates from other terpenes. CONCLUSION: Terpenes have different degradation rates, even though they are structurally similar. In addition, cultivar- and growth-condition-specific enantiomeric ratios were observed in C. sativa L., confirming that enantiomer production is species-specific and has to be considered for therapeutical applications.

6.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892037

RESUMO

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.


Assuntos
Adenosina , Doença da Artéria Coronariana , Humanos , Adenosina/metabolismo , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/tratamento farmacológico , Animais , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia
7.
Catheter Cardiovasc Interv ; 101(6): 1128-1133, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36994878

RESUMO

OBJECTIVES: The current study sought to determine whether low-dose dobutamine stress echocardiography (DSE) during transcatheter edge-to-edge mitral valve repair (TMVR) can predict residual mitral regurgitation (MR) at discharge. BACKGROUND: In most patients, TMVR can successfully reduce MR from severe to mild or moderate. However, general anesthesia during the intervention affects hemodynamics and MR assessment. At discharge transthoracic echocardiogram residual MR (>moderate) is present in 10%-30% of patients which is associated with worse clinical outcome. METHODS: In consecutive patients the severity of MR was determined at baseline, immediately after TMVR clip implantation and subsequently during low-dose DSE (both under general anesthesia) and at discharge. RESULTS: A total of 39 patients were included (mean age 76.1 ± 8.1 years, 39% male, 56% functional MR, 41% left ventricular ejection fraction < 45%). An increase of MR during DSE was seen in 11 patients, of whom 6 (55%) showed >moderate MR at discharge. None of the 28 patients without an increase of MR during DSE showed >moderate MR at discharge. The diagnostic performance of the test could be established at a sensitivity of 100% and a specificity of 85% in unselected patients. CONCLUSIONS: DSE during TMVR is a useful tool to predict residual MR at discharge. It could support procedural decision making, including implantation of additional clips and thus potentially improve clinical outcome.


Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/etiologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Volume Sistólico , Ecocardiografia sob Estresse , Resultado do Tratamento , Função Ventricular Esquerda , Cateterismo Cardíaco/efeitos adversos
8.
Pharm Res ; 40(6): 1435-1446, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36414838

RESUMO

This study applies an emerging analytical technology, wNMR (water proton nuclear magnetic resonance), to assess the stability of aluminum adjuvants and antigen-adjuvant complexes against physical stresses, including gravitation, flow and freeze/thaw. Results from wNMR are verified by conventional analytical technologies, including static light scattering and microfluidic imaging. The results show that wNMR can quickly and noninvasively determine whether an aluminum adjuvant or antigen-adjuvant complex sample has been altered by physical stresses.


Assuntos
Adjuvantes Imunológicos , Alumínio , Alumínio/química , Adjuvantes Imunológicos/química , Antígenos/química
9.
J Cardiovasc Magn Reson ; 25(1): 29, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308923

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. METHODS: Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m2 (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters. RESULTS: Of 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0-8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50-20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83-7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049). CONCLUSIONS: In patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.


Assuntos
Meios de Contraste , Dermopatia Fibrosante Nefrogênica , Masculino , Humanos , Feminino , Gadolínio , Prognóstico , Estudos Retrospectivos , Valor Preditivo dos Testes , Espectroscopia de Ressonância Magnética
10.
J Nucl Cardiol ; 30(6): 2303-2313, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37861920

RESUMO

OBJECTIVE: To assess the frequency, change in prevalence, and prognostic significance of dyspnea among contemporary patients referred for cardiac stress testing. PATIENTS AND METHODS: We evaluated the prevalence of dyspnea and its relationship to all-cause mortality among 33,564 patients undergoing stress/rest SPECT-MPI between January 1, 2002 and December 31, 2017. Dyspnea was assessed as a single-item question. Patients were divided into three temporal groups. RESULTS: The overall prevalence of dyspnea in our cohort was 30.2%. However, there was a stepwise increase in the temporal prevalence of dyspnea, which was present in 25.6% of patients studied between 2002 and 2006, 30.5% of patients studied between 2007 and 2011, and 38.7% of patients studied between 2012 and 2017. There was a temporal increase in the prevalence of dyspnea in each age, symptom, and risk factor subgroup. The adjusted hazard ratio for mortality was higher among patients with dyspnea vs those without dyspnea both among all patients, and within each chest pain subgroup. CONCLUSIONS: Dyspnea has become increasingly prevalent among patients referred for cardiac stress testing and is now present among nearly two-fifths of contemporary cohorts referred for stress-rest SPECT-MPI. Prospective study is needed to standardize the assessment of dyspnea and evaluate the reasons for its increasing prevalence.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Teste de Esforço/efeitos adversos , Dor no Peito/diagnóstico , Prognóstico , Tomografia Computadorizada de Emissão de Fóton Único/efeitos adversos , Dispneia/diagnóstico , Dispneia/etiologia , Imagem de Perfusão do Miocárdio/efeitos adversos , Doença da Artéria Coronariana/complicações
11.
J Nucl Cardiol ; 30(1): 324-334, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35484468

RESUMO

BACKGROUND: The likelihood of ischemia on myocardial perfusion imaging is central to physician decisions regarding test selection, but dedicated risk scores are lacking. We derived and validated two novel ischemia risk scores to support physician decision making. METHODS: Risk scores were derived using 15,186 patients and validated with 2,995 patients from a different center. Logistic regression was used to assess associations with ischemia to derive point-based and calculated ischemia scores. Predictive performance for ischemia was assessed using area under the receiver operating characteristic curve (AUC) and compared with the CAD consortium basic and clinical models. RESULTS: During derivation, the calculated ischemia risk score (0.801) had higher AUC compared to the point-based score (0.786, p < 0.001). During validation, the calculated ischemia score (0.716, 95% CI 0.684- 0.748) had higher AUC compared to the point-based ischemia score (0.699, 95% CI 0.666- 0.732, p = 0.016) and the clinical CAD model (AUC 0.667, 95% CI 0.633- 0.701, p = 0.002). Calibration for both ischemia scores was good in both populations (Brier score  < 0.100). CONCLUSIONS: We developed two novel risk scores for predicting probability of ischemia on MPI which demonstrated high accuracy during model derivation and in external testing. These scores could support physician decisions regarding diagnostic testing strategies.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Curva ROC , Fatores de Risco , Imagem de Perfusão do Miocárdio/métodos , Reprodutibilidade dos Testes , Doença da Artéria Coronariana/diagnóstico , Angiografia Coronária/métodos
12.
BMC Cardiovasc Disord ; 23(1): 65, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737711

RESUMO

BACKGROUND: Many hemodynamic parameters provide limited information regarding obstructive coronary artery disease (CAD) during exercise stress testing particularly when exercise is suboptimal. Hemodynamic gain index (HGI) is a recent sensitive indicator of ischemia and has been associated with increased mortality. This study evaluated the clinical impact of HGI in patients who underwent concomitant exercise stress testing and coronary computed tomography angiography (CCTA). METHODS: A total of 284 consecutive patients from the executive health program between 2010 and 2018 were identified. Resting and peak heart rate (HR) as well as systolic blood pressure (SBP) measurements were recorded. Framingham risk score (FRS), Duke treadmill score (DTS) and HGI [Formula: see text] were calculated. The latter was divided into quartiles. CCTA was used as a reference test to detect any CAD. Multivariate analysis and artificial neural network were used to determine the independent predictors of obstructive CAD. RESULTS: Mean age was 53 ± 12 years with 83% male. Mean HGI was 1.74 ± 0.67, with cut-off value of severely blunted HGI ≤ 1.25 (Quartile 4). Patients with severely blunted HGI were older, had higher FRS, and worse DTS. Patients with obstructive CAD had lower HGI when compared to those with normal CCTA/non-obstructive CAD (1.36 ± 0.53 vs. 1.77 ± 0.67, P = 0.005), and showed a higher prevalence of severely blunted HGI (44% vs. 22%, P = 0.019). After adjusting for traditional risk factors, HGI remained an independent predictor of obstructive CAD while severely blunted HGI was associated with threefold increased odds of having obstructive CAD (P = 0.05). Using artificial intelligence analysis, severely blunted HGI independently predicted obstructive CAD with an area under the curve of 0.83 and 0.96, and normalized importance of HGI of 100% and 63%, respectively for different models. CONCLUSIONS: Among patients who underwent concomitant exercise stress testing and CCTA, severely blunted HGI independently predicted obstructive CAD after multivariate adjustment for traditional risk factors.


Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Relevância Clínica , Inteligência Artificial , Hemodinâmica , Valor Preditivo dos Testes
13.
Eur Heart J Suppl ; 25(Suppl C): C63-C67, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37125276

RESUMO

Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an 'ecumenic' and 'omnivorous' functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

14.
Curr Cardiol Rep ; 25(3): 89-95, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36787025

RESUMO

PURPOSE OF REVIEW: This review summarizes the current management of patients with newly diagnosed aortic stenosis. RECENT FINDINGS: Recent developments include detection of early myocardial dysfunction using serum B-type natriuretic peptide levels and global longitudinal strain, as well as ongoing trials of transcatheter aortic valve replacement in asymptomatic patients and patients with moderate aortic stenosis complicated by symptoms or left ventricular systolic dysfunction. Given the high mortality associated with severe symptomatic aortic stenosis, all symptomatic patients should be referred for aortic valve replacement. Asymptomatic patients with left ventricular systolic dysfunction, abnormal exercise stress test, high degree of stenosis, rapid disease progression, or elevated serum B-type natriuretic peptide level may also have an indication for valve replacement, based on established criteria. The progress in management of severe aortic stenosis has been in the direction of earlier detection and earlier valve replacement.


Assuntos
Estenose da Valva Aórtica , Disfunção Ventricular Esquerda , Humanos , Peptídeo Natriurético Encefálico , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Valva Aórtica/cirurgia , Medição de Risco , Índice de Gravidade de Doença
15.
Biomed Chromatogr ; 37(9): e5688, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37325866

RESUMO

Lacosamide (LA) is an antiepileptic medicine that is used to treat tonic-clonic seizures, partial-onset seizures, mental problems, and pain. A simple, effective, and reliable normal-phase liquid chromatographic technique was developed and validated to separate and estimate the enantiomer of (S-enantiomer) LA in pharmaceutical drug substance and drug product. Normal-phase LC was performed using USP L40 packing material (250 × 4.6 mm, 5 µm) and a mobile phase of n-hexane and ethanol at 1.0 ml min-1 . The detection wavelength, column temperature, and injection volume used were 210 nm, 25°C, and 20 µl, respectively. The enantiomers (LA and S-enantiomer) were completely separated using a minimum resolution of 5.8 and accurately quantified without any interference in a 25-min run time. Accuracy study for stereoselective and enantiomeric purity trials was conducted between 10 and 200%, with recovery values ranging from 99.4 to 103.1% and linear regression values >0.997. The stability-indicating characteristics were assessed using forced degradation tests. The proposed normal-phase HPLC technique is an alternate approach to the official monograph methods (USP and Ph.Eur.) of LA, and it was successfully used in the evaluation of release and stability samples for both tablet dosage forms and pharmaceutical substances.


Assuntos
Anticonvulsivantes , Cromatografia Líquida de Alta Pressão/métodos , Lacosamida , Cromatografia Líquida , Comprimidos
16.
Biomed Chromatogr ; 37(2): e5549, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36409057

RESUMO

Apalutamide, an androgen receptor inhibitor, is used to treat prostate cancer. A stability-indicating high-performance liquid chromatography method was developed for the estimation of assay and organic impurities of apalutamide in drug substance and in tablet dosages using Design of Experiments. The chromatographic separation was achieved within 30 min using Atlantis dC18 , 100 × 4.6 mm, 3.0 µm and the binary gradient program (10 mm KH2 PO4 , pH 3.5; acetonitrile). The detection wavelength, flow rate, column temperature and injection volume used were 270 nm, 1.0 ml/min, 45°C and 10 µl, respectively. The interaction of independent variables (pH, column temperature and flow rate) and their influences on HPLC parameters were studied using a central composite design, and then the peak separation and elution behaviors between apalutamide and its seven impurities were determined. The method validation was performed for linearity, detection limit, quantitation limit, accuracy, precision and robustness as per the International Conference on Harmonization. A high-quality recovery with good precision (91.7-106.0%) and correlations (r2 > 0.997) within a linear range of 0.12-2.24 µg/ml (0.05-0.3%, w/w) were achieved consistently for assay and organic impurities of apalutamide. The stability-indicating characteristics of the proposed method were assessed through forced degradation and mass balance studies. An effort was made to figure out the chemical structures of newly formed degradation products (DP1-DP5) using LC-MS/MS.


Assuntos
Antineoplásicos , Espectrometria de Massas em Tandem , Masculino , Humanos , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Contaminação de Medicamentos , Estabilidade de Medicamentos , Reprodutibilidade dos Testes
17.
Pediatr Cardiol ; 44(7): 1605-1612, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37344558

RESUMO

Myocarditis is common in Multisystem Inflammatory Syndrome in Children (MIS-C), and the mechanism may differ from idiopathic/viral myocarditis as MIS-C involves a hyper-inflammatory state weeks after COVID-19. We sought to evaluate exercise stress testing (EST) in these patients as EST may help guide return-to-play recommendations. Retrospective cohort study evaluating ESTs (standard Bruce treadmill protocol) from MIS-C patients from 2020 to 2022, compared to myocarditis patients and age, sex, and weight matched controls from 2005 to 2019. ESTs included 22 MIS-C patients (mean age 11.9 years) with 14 cardiopulmonary and 8 cardiovascular tests, 33 myocarditis (15.5 years), and 44 controls (12.0 years). Percent-predicted peak VO2 was abnormal (< 80% predicted) in 11/14 (79%) MIS-C patients, 13/33 (39%) myocarditis, and 17/44 (39%) controls (p = 0.04). Exercise duration was shorter in MIS-C than myocarditis or control cohorts (p = 0.01). Isolated atrial or ventricular ectopy was seen in 8/22 (36%) MIS-C, 9/33 (27%) myocarditis, and 5/44 (11%) controls (p = 0.049). No arrhythmias/complex ectopy or evidence of ischemia were noted, though non-specific ST/T wave abnormalities occurred in 4/22 (18%) MIS-C, 5/33 (15%) myocarditis, and 3/44 (7%) controls. Exercise duration and percent-predicted peak VO2 were significantly reduced in MIS-C at mean 6-month follow-up compared to pre-COVID era idiopathic/viral myocarditis and control cohorts. This may be secondary to deconditioning during the pandemic and/or chronic cardiopulmonary or autonomic effects of COVID/MIS-C. Although there were no exercise-induced arrhythmias in our MIS-C patients, larger cohort studies are warranted. EST in MIS-C follow-up may help evaluate safety and timing of return to play and potentially mitigate further deconditioning.


Assuntos
COVID-19 , Miocardite , Criança , Humanos , Seguimentos , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
18.
Knee Surg Sports Traumatol Arthrosc ; 31(11): 4886-4894, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37572141

RESUMO

PURPOSE: Acute syndesmotic ankle injuries continue to impose a diagnostic dilemma and it remains unclear whether weightbearing and/or external rotation should be added during the imaging process. Therefore, the aim of this study was to assess if combined weightbearing and external rotation increases the diagnostic sensitivity of syndesmotic ankle instability using weightbearing CT (WBCT) imaging, compared to isolated weightbearing. METHODS: In this retrospective study, patients with an acute syndesmotic ankle injury were analysed using a WBCT (N = 21; Age = 31.6 ± 14.1 years old). Inclusion criteria were an MRI confirmed syndesmotic ligament injury imaged by a WBCT of the ankle during weightbearing and combined weightbearing-external rotation. Exclusion criteria consisted of fracture associated syndesmotic injuries. Three-dimensional (3D) models were generated from the CT slices. Tibiofibular displacement and talar rotation were quantified using automated 3D measurements (anterior tibiofibular distance (ATFD), Alpha angle, posterior Tibiofibular distance (PTFD) and Talar rotation (TR) angle in comparison to the contralateral non-injured ankle. RESULTS: The difference in neutral-stressed Alpha angle and ATFD showed a significant difference between patients with a syndesmotic ankle lesion and contralateral control (P = 0.046 and P = 0.039, respectively). The difference in neutral-stressed PTFD and TR angle did not show a significant difference between patients with a syndesmotic ankle lesion and healthy ankles (n.s.). CONCLUSION: Application of combined weightbearing-external rotation reveals an increased ATFD in patients with syndesmotic ligament injuries. This study provides the first insights based on 3D measurements to support the potential relevance of applying external rotation during WBCT imaging. In clinical practice, this could enhance the current diagnostic accuracy of subtle syndesmotic instability in a non-invasive manner. However, to what extent certain displacement patterns require operative treatment strategies has yet to be determined in future studies. LEVEL OF EVIDENCE: Level III.

19.
Neth Heart J ; 31(11): 444-451, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37347419

RESUMO

BACKGROUND: In sudden cardiac arrest survivors without an immediately identifiable cause, additional extensive yet individualised testing is required. METHODS: We describe 3 survivors of sudden cardiac arrest in whom exercise stress testing was not performed during the initial hospital admission. RESULTS: All 3 patients were incorrectly diagnosed with long QT syndrome based on temporary sudden cardiac arrest-related heart rate-corrected QT interval prolongation, and exercise stress testing was not performed during the initial work-up. When they were subjected to exercise stress testing during follow-up, a delayed diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was made. As a result, these patients were initially managed inappropriately, and their family members were initially not screened for CPVT. CONCLUSION: In sudden cardiac arrest survivors without an immediately identifiable cause, omission of exercise stress testing or erroneous interpretation of the results can lead to a delayed or missed diagnosis of CPVT, which may have considerable implications for survivors and their family.

20.
Khirurgiia (Mosk) ; (10): 88-97, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37916562

RESUMO

OBJECTIVE: To assess the role of cardiopulmonary exercise testing in examination of patients with high risk of respiratory complications in anatomical resections for non-small cell lung cancer. MATERIAL AND METHODS: A non-randomized retrospective single-center study was devoted to immediate results of surgical treatment of patients with NSCLC between December 2020 and April 2021. Median age of patients was 65 (84; 30) years, male-to-female ratio - 129 (57%)/98 (43%). All patients were examined according to a unified algorithm recommended by the American (ATS) and European (ESTS) societies of thoracic surgeons. At the first stage, we analyzed airflow rate and performed non-invasive exercise tests (6-minute walk and/or stair test). Resections of lungs were performed in 231 patients, anatomic lung resections - in 227 patients (lobectomy - 199, bilobectomy - 4, segmentectomy - 17, pneumonectomy - 7). We excluded 4 patients who underwent non-anatomic lung resections (marginal resections). RESULTS: Among 236 patients referred for anatomical lung resections, 34 (14.4%) ones were selected for cardiopulmonary testing. Selection was based on low exercise tolerance and/or severe decrease in predictive respiratory parameters (FEV<50%). Patients were divided into 4 groups depending on peak oxygen consumption. There were 5 (2%), 10 (29.4%), 11 (32.3%) and 8 (23.5%) patients with extremely high, high, moderate and low risk of respiratory complications, respectively. Surgeries were performed for IA1 (n=6), IA2 (n=50), IA3 (n=37), IB (n=31), IIA (n=19), IIB (n=37), IIIA (n=25) and IIIB (n=4) stages. The overall incidence of postoperative complications was 23% (95% CI: 18-28.8). Complications Clavien-Dindo grade I, IIIA, IIIB, IVA, IVB and V prevailed in both groups. Median postoperative hospital-stay (6 (6; 8) vs. 7 (6; 8) days) and time of pleural drainage (4 (2; 5) vs. 3 (3; 4) days) were similar. Organ-sparing procedures prevailed in the main group (5 (26%) out of 19 (95% CI: 11.81-48.8) vs. 12 (6.7%) out of 180 (95% CI: 3.8-11.3)). Overall mortality (n=231) was 1.7% (95% CI: 0.7-4.4). Mortality throughout the first postoperative year was 24% (95% CI: 12.2-42.1) and 7.4% (95% CI: 4.2-11.3), respectively. CONCLUSION: Cardiopulmonary exercise testing makes it possible to objectively assess exercise tolerance and identify high-risk patients for respiratory complications. These data are valuable when planning the treatment of patients with non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Teste de Esforço/efeitos adversos , Estudos Retrospectivos , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
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