RESUMO
PURPOSE OF REVIEW: The purpose of this review is to highlight the increasing importance of cardiac magnetic resonance (CMR) imaging in diagnosing and managing cardiac amyloidosis, especially given the recent advancements in treatment options. RECENT FINDINGS: This review emphasizes the crucial role of late gadolinium enhancement (LGE) with phase-sensitive inversion recovery (PSIR) techniques in both diagnosing and predicting patient outcomes in cardiac amyloidosis. The review also explores promising new techniques for diagnosing early-stage disease, such as native T1 mapping and ECV quantification. Additionally, it delves into experimental techniques like diffusion tensor imaging, MR elastography, and spectroscopy. SUMMARY: This review underscores CMR as a powerful tool for diagnosing cardiac amyloidosis, assessing risk factors, and monitoring treatment response. While LGE imaging remains the current best practice for diagnosis, emerging techniques such as T1 mapping and ECV quantification offer promise for improved detection, particularly in early stages of the disease. This has significant implications for patient management as newer therapeutic options become available for cardiac amyloidosis.
Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/diagnóstico , Amiloidose/diagnóstico por imagem , Cardiomiopatias/diagnóstico , Cardiomiopatias/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Meios de ContrasteRESUMO
The active form of kinases is shared across different family members, as are several commonly observed inactive forms. We previously performed a clustering of the conformation of the activation loop of all protein kinase structures in the Protein Data Bank (PDB) into eight classes based on the dihedral angles that place the Phe side chain of the DFG motif at the N-terminus of the activation loop. Our clusters are strongly associated with the placement of the activation loop, the C-helix, and other structural elements of kinases. We present Kincore, a web resource providing access to our conformational assignments for kinase structures in the PDB. While other available databases provide conformational states or drug type but not both, KinCore includes the conformational state and the inhibitor type (Type 1, 1.5, 2, 3, allosteric) for each kinase chain. The user can query and browse the database using these attributes or determine the conformational labels of a kinase structure using the web server or a standalone program. The database and labeled structure files can be downloaded from the server. Kincore will help in understanding the conformational dynamics of these proteins and guide development of inhibitors targeting specific states. Kincore is available at http://dunbrack.fccc.edu/kincore.
Assuntos
Bases de Dados de Proteínas , Inibidores de Proteínas Quinases/classificação , Proteínas Quinases/classificação , Software , Conformação Proteica , Inibidores de Proteínas Quinases/química , Proteínas Quinases/químicaRESUMO
AIMS: Cardiac implantable electronic devices (CIED) are important tools for managing arrhythmias, improving hemodynamics, and preventing sudden cardiac death. Device-related infections (DRI) remain a significant complication of CIED and are associated with major adverse outcomes. We aimed to assess the trend in CIED implantations, and the burden and morbidity associated with DRI. METHODS AND RESULTS: The 2011-2018 National Inpatient Sample database was searched for admissions for CIED implantation and DRI. A total of 1 604 173 admissions for CIED implantations and 71 007 (4.4%) admissions for DRI were reported. There was no significant change in annual admission rates for DRI (3.96-4.59%, P value for trend = 0.98). Those with DRI were more likely to be male (69.3 vs. 57%, P < 0.001) and have a Charlson comorbidity index score ≥3 (46.6 vs. 36.8%, P < 0.001). The prevalence of congestive heart failure (CHF) increased in those admitted with DRI over the observation period. Pulmonary embolism, deep vein thrombosis, and post-procedural hematoma were the most common complications in those with DRI (4.1, 3.6, and 2.90%, respectively). Annual in-hospital mortality for those with DRI ranged from 3.9 to 5.8% (mean 4.4%, P value for trend = 0.07). Multivariate analysis identified CHF [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.35-2.07], end-stage renal disease (OR = 1.90; 95% CI = 1.46-2.48), coagulopathy (OR = 2.94; 95% CI = 2.40-3.61), and malnutrition (OR = 2.50; 95% CI = 1.99-3.15) as the predictors of in-hospital mortality for patients admitted with DRI. CONCLUSION: Device-related infection is relatively common and continues to be associated with high morbidity and mortality. The prevalence of DRI has not changed significantly despite technical and technological advances in cardiac devices and their implantation.
Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Humanos , Masculino , Feminino , Desfibriladores Implantáveis/efeitos adversos , Estudos Retrospectivos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/terapia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Hospitalização , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Marca-Passo Artificial/efeitos adversos , Fatores de RiscoRESUMO
Targeting protein kinases is an important strategy for intervention in cancer. Inhibitors are directed at the active conformation or a variety of inactive conformations. While attempts have been made to classify these conformations, a structurally rigorous catalog of states has not been achieved. The kinase activation loop is crucial for catalysis and begins with the conserved DFGmotif. This motif is observed in two major classes of conformations, DFGin-a set of active and inactive conformations where the Phe residue is in contact with the C-helix of the N-terminal lobe-and DFGout-an inactive form where Phe occupies the ATP site exposing the C-helix pocket. We have developed a clustering of kinase conformations based on the location of the Phe side chain (DFGin, DFGout, and DFGinter or intermediate) and the backbone dihedral angles of the sequence X-D-F, where X is the residue before the DFGmotif, and the DFG-Phe side-chain rotamer, utilizing a density-based clustering algorithm. We have identified eight distinct conformations and labeled them based on the Ramachandran regions (A, alpha; B, beta; L, left) of the XDF motif and the Phe rotamer (minus, plus, trans). Our clustering divides the DFGin group into six clusters including BLAminus, which contains active structures, and two common inactive forms, BLBplus and ABAminus. DFGout structures are predominantly in the BBAminus conformation, which is essentially required for binding type II inhibitors. The inactive conformations have specific features that make them unable to bind ATP, magnesium, and/or substrates. Our structurally intuitive nomenclature will aid in understanding the conformational dynamics of kinases and structure-based development of kinase drugs.
Assuntos
Algoritmos , Modelos Moleculares , Proteínas Quinases , Domínio Catalítico , Inibidores de Proteínas Quinases/química , Proteínas Quinases/química , Proteínas Quinases/genética , Estrutura Secundária de Proteína , Especificidade por Substrato , Terminologia como AssuntoRESUMO
BACKGROUND: Adults with congenital heart disease (CHD) awaiting heart transplant (HT) have higher mortality and waitlist removal due to clinical deterioration than those without CHD. The selective use of non-lung donors (NLD) to recover donor pulmonary vasculature to assist in graft implantation may be a contributing factor and is supported by consensus statements despite the recent use of pericardium or graft material as an alternative in pulmonary vascular reconstruction. The impact of selecting NLD for CHD recipients on wait time and mortality has not been evaluated. METHODS/RESULTS: In the United Network for Organ Sharing (UNOS) Registry, 1271 HT recipients age ≥ 18 with CHD were identified between 1987 and 2016, 68% of which had NLDs. Prior to HT, NLD recipients were significantly less likely to be listed UNOS Status 1A, require mechanical ventilation, or intra-aortic balloon pump support. There was no difference in mean waitlist time (254 vs. 278 days, p = .31), 1-year mortality (82% vs. 80%, p = .81; adjusted odds ratio 1.32, 95% confidence interval [CI] 0.96-1.83, p = .08), or overall mortality (adjusted hazard ratio 1.08, 95% CI 0.86-1.36, p = .48) between recipients from NLD and concomitant lung donors. CONCLUSIONS: Adult CHD patients who are less critically ill or listed at a lower status are more likely to receive HT from NLD. There is no overall mortality benefit associated with this practice. While specific cases may necessitate waiting for NLD, programs need to re-evaluate whether this should remain a more widespread practice among CHD patients.
Assuntos
Cardiopatias Congênitas , Transplante de Coração , Adulto , Humanos , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos , Estados Unidos , Listas de EsperaRESUMO
CASP11 (the 11th Meeting on the Critical Assessment of Protein Structure Prediction) ran a blind experiment in the refinement of protein structure predictions, the fourth such experiment since CASP8. As with the previous experiments, the predictors were provided with one starting structure from the server models of each of a selected set of template-based modeling targets and asked to refine the coordinates of the starting structure toward native. We assessed the refined structures with the Z-scores of the standard CASP measures, which compare the model-target similarities of the models from all the predictors. Furthermore, we assessed the refined structures with "relative measures," which compare the improvement in accuracy of each model with respect to the starting structure. The latter provides an assessment of the extent to which each predictor group is able to improve the starting structures toward native. We utilized heat maps to display improvements in the Calpha-Calpha distance matrix for each model. The heat maps labeled with each element of secondary structure helped us to identify regions of refinement toward native in each model. Most positively scoring models show modest improvements in multiple regions of the structure, while in some models we were able to identify significant repositioning of N/C-terminal segments and internal elements of secondary structure. The best groups were able to improve more than 70% of the targets from the starting models, and by an average of 3-5% in the standard CASP measures. Proteins 2016; 84(Suppl 1):260-281. © 2016 Wiley Periodicals, Inc.
Assuntos
Benchmarking , Biologia Computacional/estatística & dados numéricos , Modelos Moleculares , Modelos Estatísticos , Proteínas/química , Software , Algoritmos , Motivos de Aminoácidos , Biologia Computacional/métodos , Simulação por Computador , Bases de Dados de Proteínas , Humanos , Internet , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Estrutura Terciária de Proteína , Homologia Estrutural de Proteína , TermodinâmicaRESUMO
We present the assessment of predictions submitted in the template-based modeling (TBM) category of CASP11 (Critical Assessment of Protein Structure Prediction). Model quality was judged on the basis of global and local measures of accuracy on all atoms including side chains. The top groups on 39 human-server targets based on model 1 predictions were LEER, Zhang, LEE, MULTICOM, and Zhang-Server. The top groups on 81 targets by server groups based on model 1 predictions were Zhang-Server, nns, BAKER-ROSETTASERVER, QUARK, and myprotein-me. In CASP11, the best models for most targets were equal to or better than the best template available in the Protein Data Bank, even for targets with poor templates. The overall performance in CASP11 is similar to the performance of predictors in CASP10 with slightly better performance on the hardest targets. For most targets, assessment measures exhibited bimodal probability density distributions. Multi-dimensional scaling of an RMSD matrix for each target typically revealed a single cluster with models similar to the target structure, with a mode in the GDT-TS density between 40 and 90, and a wide distribution of models highly divergent from each other and from the experimental structure, with density mode at a GDT-TS value of â¼20. The models in this peak in the density were either compact models with entirely the wrong fold, or highly non-compact models. The results argue for a density-driven approach in future CASP TBM assessments that accounts for the bimodal nature of these distributions instead of Z scores, which assume a unimodal, Gaussian distribution. Proteins 2016; 84(Suppl 1):200-220. © 2016 Wiley Periodicals, Inc.
Assuntos
Biologia Computacional/estatística & dados numéricos , Modelos Moleculares , Modelos Estatísticos , Proteínas/química , Software , Algoritmos , Animais , Archaea/química , Bactérias/química , Biologia Computacional/métodos , Simulação por Computador , Bases de Dados de Proteínas , Drosophila melanogaster/química , Humanos , Internet , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Homologia Estrutural de Proteína , Vírus/químicaRESUMO
In CASP11, the organizers sought to bring the biological inferences from predicted structures to the fore. To accomplish this, we assessed the models for their ability to perform quantifiable tasks related to biological function. First, for 10 targets that were probable homodimers, we measured the accuracy of docking the models into homodimers as a function of GDT-TS of the monomers, which produced characteristic L-shaped plots. At low GDT-TS, none of the models could be docked correctly as homodimers. Above GDT-TS of â¼60%, some models formed correct homodimers in one of the largest docked clusters, while many other models at the same values of GDT-TS did not. Docking was more successful when many of the templates shared the same homodimer. Second, we docked a ligand from an experimental structure into each of the models of one of the targets. Docking to the models with two different programs produced poor ligand RMSDs with the experimental structure. Measures that evaluated similarity of contacts were reasonable for some of the models, although there was not a significant correlation with model accuracy. Finally, we assessed whether models would be useful in predicting the phenotypes of missense mutations in three human targets by comparing features calculated from the models with those calculated from the experimental structures. The models were successful in reproducing accessible surface areas but there was little correlation of model accuracy with calculation of FoldX evaluation of the change in free energy between the wild-type and the mutant. Proteins 2016; 84(Suppl 1):370-391. © 2016 Wiley Periodicals, Inc.
Assuntos
Amidoidrolases/química , Proteínas Quinases Dependentes de AMP Cíclico/química , Proteína gp120 do Envelope de HIV/química , Fator de Crescimento de Hepatócito/química , Modelos Estatísticos , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas/química , Amidoidrolases/genética , Amidoidrolases/metabolismo , Sítios de Ligação , Biologia Computacional/métodos , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/metabolismo , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Ligantes , Mutação de Sentido Incorreto , Fenótipo , Ligação Proteica , Domínios Proteicos , Dobramento de Proteína , Multimerização Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade , TermodinâmicaRESUMO
Proteins belonging to Bcl-2 family regulate intrinsic cell death pathway. Although mammalian antiapoptotic Bcl-2 members interact with multiple proapoptotic proteins, the Caenorhabditis elegans Bcl-2 homolog CED-9 is known to have only two proapoptotic partners. The BH3-motif of proapoptotic proteins bind to the hydrophobic groove of prosurvival proteins formed by the Bcl-2 helical fold. CED-9 is also known to interact with CED-4, a homolog of the human cell death activator Apaf1. We have performed molecular dynamics simulations of CED-9 in two forms and compared the results with those of mammalian counterparts Bcl-XL, Bcl-w, and Bcl-2. Our studies demonstrate that the region forming the hydrophobic cleft is more flexible compared with the CED-4-binding region, and this is generally true for all antiapoptotic Bcl-2 proteins studied. CED-9 is the most stable protein during simulations and its hydrophobic pocket is relatively rigid explaining the absence of functional redundancy in CED-9. The BH3-binding region of Bcl-2 is less flexible among the mammalian proteins and this lends support to the studies that Bcl-2 binds to less number of BH3 peptides with high affinity. The C-terminal helix of CED-9 lost its helical character because of a large number of charged residues. We speculate that this region probably plays a role in intracellular localization of CED-9. The BH4-motif accessibility in CED-9 and Bcl-w is controlled by the loop connecting the first two helices. Although CED-9 adopts the same Bcl-2 fold, our studies highlight important differences in the dynamic behavior of CED-9 and mammalian antiapoptotic homologs.
Assuntos
Proteínas de Caenorhabditis elegans/química , Caenorhabditis elegans , Simulação de Dinâmica Molecular , Proteínas Proto-Oncogênicas c-bcl-2/química , Animais , Sítios de Ligação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Homologia Estrutural de ProteínaRESUMO
Giant coronary artery aneurysm (GCA) is a rare disease afflicting 0.2% of the population. It is primarily attributed to atherosclerosis in adults and Kawasaki disease in children. Other uncommon etiologies include Takayasu arteritis and post-percutaneous coronary intervention.1,2 GCA lacks a universally accepted definition, with proposed criteria including a diameter exceeding 2 cm, 5 cm, or four times the normal vessel size.3 While the majority of GCAs are asymptomatic, a subset of patients present with angina, myocardial infarction from embolization or compression, heart failure due to fistula formation, or even sudden death.1 We report a case of an adult harboring a GCA involving the right coronary artery.
Assuntos
Aterosclerose , Aneurisma Coronário , Adulto , Criança , Humanos , Vasos Coronários , Dor , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Aneurisma Coronário/terapia , Extremidade SuperiorRESUMO
BACKGROUND: Septic patients are predisposed to myocardial injury manifested as cardiac troponin release (TnR). Prognostic significance and management implications of TnR and its relationship to fluid resuscitation and outcomes in the intensive care unit (ICU) setting has not been fully elucidated. METHODS: A total of 24,778 patients with sepsis from eICU-CRD, MIMIC-III and MIMIC-IV databases were included in this retrospective study. In-hospital mortality and one-year survival were examined using multivariable regression analysis and Kaplan-Meier survival analysis with overlap weighting adjustment, as well as generalized additive models for fluid resuscitation. RESULTS: TnR on admission was associated with higher in-hospital mortality [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.23-1.43; p < 0.001 in unweighted analysis and adjusted OR = 1.39; 95% CI = 1.29-1.50; P < 0.001 with overlap weighting]. One-year mortality was higher in patients with admission TnR (P = 0.002). A trend was noted for association between admission TnR and 1-year mortality [adjusted OR = 1.16; 95% CI = 0.99-1.37; P = 0.067 in unweighted analysis] while the association was statistically significant after overlap weighting (adjusted OR = 1.25; 95% CI = 1.06-1.47; P = 0.008). Patients with admission TnR were less likely to benefit from more liberal fluid resuscitation. Adequate fluid resuscitation (80 ml/kg in the first 24 h of ICU stay) was associated with lower in-hospital mortality in septic patients without TnR but not in those with admission TnR. CONCLUSIONS: Admission TnR is significantly associated with higher in-hospital mortality and 1-year mortality among septic patients. Adequate fluid resuscitation improves in-hospital mortality in septic patients without but not with admission TnR.
Assuntos
Sepse , Choque Séptico , Humanos , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/terapia , Prognóstico , Unidades de Terapia Intensiva , Hidratação , Troponina , RessuscitaçãoRESUMO
There is limited data on the impact of atrial fibrillation (Afib) on hospital outcomes in females with peripartum cardiomyopathy (PPCM). The National Inpatient Sample (NIS) 2011-2019 was used to find patients with PPCM. PPCM patients were divided into 2 groups: with and without Afib. Baseline characteristics were compared between both groups. Logistic regression was used to find independent predictors of Afib. Out of 13,840 PPCM patients, 249 (1.8%) also had a diagnosis of Afib. The Afib group was older and had a high burden of comorbidities. PPCM patients with Afib had higher in-hospital mortality (4-vs-0.7%, P=0.02), mean length of stay (11.3-vs-4.3 days, P<0.001) and healthcare resource utilization. Old age, low-income quartile, liver disease, obstructive sleep apnea, and acute posthemorrhagic anemia were significant predictors of Afib. In conclusion, Afib is associated with higher in-hospital mortality and worse outcomes in females with PPCM. Further research is needed to improve these outcomes.
Assuntos
Fibrilação Atrial , Cardiomiopatias , Humanos , Feminino , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Período Periparto , Pacientes Internados , Cardiomiopatias/complicações , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Hospitais , Atenção à SaúdeRESUMO
A 75-year-old patient was incidentally found to have an intracardiac mass by echocardiography. Subsequent cardiac magnetic resonance imaging and cardiac positron emission tomography confirmed a large and possibly malignant mass extending from the right atrium into the coronary sinus. The patient underwent an intracardiac echocardiography guided biopsy, which revealed diffuse B-cell lymphoma, and is currently undergoing rituximab, etoposide, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH)-based chemotherapy.
Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Idoso , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Rituximab/uso terapêutico , Ciclofosfamida/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/uso terapêutico , Tomografia por Emissão de Pósitrons , EcocardiografiaRESUMO
BACKGROUND: Apical left ventricular (LV) aneurysms in hypertrophic cardiomyopathy (HCM) are associated with adverse outcomes. The reported frequency of mid-LV obstruction has varied from 36% to 90%. OBJECTIVES: The authors sought to ascertain the frequency of mid-LV obstruction in HCM apical aneurysms. METHODS: The authors analyzed echocardiographic and cardiac magnetic resonance examinations of patients with aneurysms from 3 dedicated programs and compared them with 63 normal controls and 47 controls with apical-mid HCM who did not have aneurysms (22 with increased LV systolic velocities). RESULTS: There were 108 patients with a mean age of 57.4 ± 13.5 years; 40 (37%) were women. A total of 103 aneurysm patients (95%) had mid-LV obstruction with mid-LV complete systolic emptying. Of the patients with obstruction, 84% had a midsystolic Doppler signal void, a marker of complete flow cessation, but only 19% had Doppler systolic gradients ≥30 mm Hg. Five patients (5%) had relative hypokinesia in mid-LV without obstruction. Aneurysm size is not bimodal but appears distributed by power law, with large aneurysms decidedly less common. Comparing mid-LV obstruction aneurysm patients with all control groups, the short-axis (SAX) systolic areas were smaller (P < 0.007), the percent SAX area change was greater (P < 0.005), the papillary muscle (PM) areas were larger (P < 0.003), and the diastolic PM areas/SAX diastolic areas were greater (P < 0.005). Patients with aneurysms had 22% greater SAX PM areas compared with those with elevated LV velocities but no aneurysms (median: 3.00 cm2 [IQR: 2.38-3.70 cm2] vs 2.45 [IQR: 1.81-2.95 cm2]; P = 0.004). Complete emptying occurs circumferentially around central PMs that contribute to obstruction. Late gadolinium enhancement was always brightest and the most transmural apical of, or at the level of, complete emptying. CONCLUSIONS: The great majority (95%) of patients in the continuum of apical aneurysms have associated mid-LV obstruction. Further research to investigate obstruction as a contributing cause to apical aneurysms is warranted.
Assuntos
Cardiomiopatia Hipertrófica , Meios de Contraste , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Valor Preditivo dos Testes , Gadolínio , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Ventrículos do Coração/diagnóstico por imagemRESUMO
Background Increased accessibility, recreational use, and regional legalization of marijuana (cannabis) have been paralleled by widespread recognition of its serious cardiovascular complications (acute myocardial infarction, stroke, sudden death) particularly in the young. We aimed to examine trends in hospital admissions and outcomes of adults with stress cardiomyopathy (SC) in temporal relation to marijuana use. Methods and results A search of the 2003-2011 Nationwide Inpatient Sample (NIIS) database identified 33,343 admissions for SC of which 210 (0.06%) were temporally related to marijuana use. Demographics, clinical characteristics, and outcomes of marijuana users (MU) and non-marijuana users (NMU) with SC were compared. MU were younger (44±14 vs. 66±13 years), more often male (36% vs. 8%), and had lower prevalence of hypertension (38% vs. 62%), diabetes (2.4% vs. 17.6%), and hyperlipidemia (16% vs. 52%) while more often suffered from depression (33% vs. 15%), psychosis (12% vs. 4%), anxiety disorder (28% vs. 16%), alcohol use disorder (13% vs. 3%), tobacco use (73% vs. 29%), and polysubstance abuse (11% vs. 0.3%) [all p<0.001]. In addition, MU more often suffered a cardiac arrest and required placement of a defibrillator while congestive heart failure was more frequent in NMU. Logistic regression analysis on the entire database (n=71,753,900), adjusted for known risk factors for SC, identified marijuana use as an independent predictor of SC (OR=1.83; 95% CI=1.57-2.12, p<0.0001). Among MU, older age (>48 years) was a strong predictor of any major adverse cardiac event (OR=7.8; 95% CI=2.88-21.13; p<0.0001). Conclusions Marijuana use is linked to SC in younger individuals and is associated with significant morbidity despite being younger in age and having a more favorable cardiac risk factor profile in affected individuals.
RESUMO
Reports of cardiac arrhythmia secondary to loperamide toxicity have become increasingly common in the literature. We present two patients in their mid-20s, each having overdosed on loperamide and subsequently manifesting life-threatening cardiac arrhythmias not otherwise explained by known pathology. An analysis of the limited research available indicates that loperamide's capacity to block ion channels may be responsible for these events. A better mechanistic understanding of loperamide's effects can help inform clinical management of patients with these life-threatening symptoms as at this time no set guidelines for management have yet been established.
RESUMO
Gastrointestinal bleed (GIB) is an important complication in patients with hypertrophic cardiomyopathy (HC) although its prevalence, predictors and outcomes are unknown. The national inpatient sample 2011 to 2018 was analyzed to find hospitalizations with the diagnosis of HC. HC patients were divided into 2 groups: with and without GIB. Baseline characteristics between the 2 groups were compared (Table 2). Variables with p value of 0.2 or less from univariate logistic regression were included in the multivariate logistic regression to find an independent predictor of GIB in HC patients. Stata IC was used for all statistical analysis. Our study reported 242,172 HC hospitalizations between 2011 and 2018, out of which 13,231 (5.4%) also has a concurrent diagnosis of GIB. The GIB group was older (mean age ± SD: 70 ± 28 vs 65 ± 10, p <0.001), more likely to be female (62.5 vs 57%, p <0.001) and had higher burden of comorbidities . HC patients with GIB had higher in-hospital mortality rate (5.3 vs 3.1%, p <0.001), mean length of stay (7.8 vs 5.6 days, p <0.001) and mean total hospital cost ($100,294 vs 77,966, p <0.001). Age group >75, female, chronic kidney disease (CKD 3/4), end-stage renal disease, cirrhosis, coagulopathy and malnutrition were an independent predictor of GIB in HC patients. In conclusion, the prevalence of GIB during HC hospitalizations is increasing. Older, white, females with higher burden of comorbidities are at an increased risk of GIB in HC patients. Sex-based disparities in the prevalence of GIB in HC patients is an area of further research.
Assuntos
Cardiomiopatia Hipertrófica/complicações , Hemorragia Gastrointestinal/epidemiologia , Pacientes Internados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Background Severe patient prosthesis mismatch (sPPM) after surgical aortic valve replacement is associated with worse outcomes. Limited data exists on the impact of sPPM on outcomes after transcatheter aortic valve replacement (TAVR), especially regarding the newer generation valves. The aim of this study was to evaluate the incidence, determinants, and outcomes of sPPM in patients undergoing TAVR with Edwards SAPIEN XT (ES XT) and Edwards SAPIEN 3 (ES3) valves (Edwards Lifesciences, Irvine, CA, USA). Methods We retrospectively reviewed 366 patients who underwent TAVR with ES XT (n = 114) or ES3 (n = 252) valves between July 2012 and June 2018. sPPM was defined as indexed effective orifice area (iEOA) <0.65 cm2/m2. Kaplan-Meier survival estimates were used to determine outcomes. Results Multivariate linear regression analysis was utilized to determine potential independent effects of PPM on outcomes. sPPM was present in 40 (11%) of the patients [8 (7%) ES XT and 32 (13%) ES3] and was associated with female sex, smaller left ventricular outflow tract (LVOT) diameter and aortic valve annular area, absence of prior coronary artery bypass graft (CABG) surgery, shorter height, higher body mass index, and smaller pre-TAVR valve area (all p < 0.05). Among those with ES3 valves, the incidence of sPPM was inversely proportional to the valve size (50%, 25%, 5% and 3% for 20-, 23-, 26- and 29-mm valve sizes, respectively; p < 0.001). At a mean follow-up period of 3.5 ± 1.5 years, there was no difference in all-cause mortality (22.5% vs. 25.6%, p = 0.89) or a composite endpoint of heart failure, arrhythmias, stroke, and myocardial infarction (30% vs. 34%, p = 0.24) in those with or without sPPM. Conclusion ES3 was associated with a higher incidence of sPPM, particularly with smaller valve sizes. However, the presence of sPPM as defined by iEOA was not an independent predictor of adverse outcomes in patients undergoing TAVR within an intermediate follow-up period.
RESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition. Chronic inflammation is associated with atherosclerosis, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), chronic kidney disease. But sparse data are available regarding the trends of cardiovascular diseases and complications in RA. We conducted a National Inpatient Sample database analysis to demonstrate the trends of cardiac complications in patients with RA. METHODS: We used National Inpatient Sample data from 2005 to 2014 to identify admissions with the diagnosis of RA and identified who had associated cardiovascular complications also. The International Classification of Diseases-9th Revision-Clinical Modification codes were used for the diagnoses of RA; congestive heart failure (CHF), acute myocardial infarction (AMI), and atrial fibrillation (AF). RESULTS: A statistically significant increasing trend of AMI, CHF, and AF was found. Independent predictors of mortality in RA patients with AMI were age (OR 1.03, CI 1.02-1.04; P < 0.001), COPD (OR 1.67, CI 1.40-2.00; P < 0.001), cerebrovascular disease (OR 2.207, CI 1.71-2.86; P < 0.001), renal disease (OR 1.42, CI 1.16-1.75; P = 0.001), and alcohol abuse (OR 2.73, CI 1.73-4.32; P < 0.001). Independent predictors of mortality in RA patients with CHF were age (odds ratio [OR] 1.02, confidence interval [CI] 1.017-1.024; P < 0.001]), COPD (OR 1.09, CI 1.01-1.18; Pâ¯=â¯0.023), cerebrovascular disease (OR 1.67, CI 1.44-1.95; P < 0.001), renal disease (OR 1.16, CI 1.07-1.27; P = 0.001). Independent predictors of mortality in RA patients with AF were age (OR 1.02, CI 1.02-1.03; P < 0.001), race (OR 1.16, CI 1.02-1.31; Pâ¯=â¯0.022), COPD (OR 1.56, CI 1.42-1.71; P < 0.001), peripheral arterial disease (OR 1.34, CI 1.16-1.53; P < 0.001), cerebrovascular disease (OR 2.27, CI 1.0-2.58; P < 0.001), renal disease (OR 1.60, CI 1.44-1.80; P < 0.001). The mortality trend has increased significantly in the CHF (Pâ¯=â¯0.025) and AF (Pâ¯=â¯0.042) groups during this study period. CONCLUSIONS: We have found a significant increase in trend of cardiovascular complications in RA patients. The proportion of patients, with cardiovascular comorbidities, have also been increased significantly.
Assuntos
Artrite Reumatoide , Fibrilação Atrial , Artrite Reumatoide/epidemiologia , Fibrilação Atrial/epidemiologia , Hospitalização , Humanos , Pacientes Internados , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Studies on the structures and functions of individual kinases have been used to understand the biological properties of other kinases that do not yet have experimental structures. The key factor in accurate inference by homology is an accurate sequence alignment. We present a parsimonious, structure-based multiple sequence alignment (MSA) of 497 human protein kinase domains excluding atypical kinases. The alignment is arranged in 17 blocks of conserved regions and unaligned blocks in between that contain insertions of varying lengths present in only a subset of kinases. The aligned blocks contain well-conserved elements of secondary structure and well-known functional motifs, such as the DFG and HRD motifs. From pairwise, all-against-all alignment of 272 human kinase structures, we estimate the accuracy of our MSA to be 97%. The remaining inaccuracy comes from a few structures with shifted elements of secondary structure, and from the boundaries of aligned and unaligned regions, where compromises need to be made to encompass the majority of kinases. A new phylogeny of the protein kinase domains in the human genome based on our alignment indicates that ten kinases previously labeled as "OTHER" can be confidently placed into the CAMK group. These kinases comprise the Aurora kinases, Polo kinases, and calcium/calmodulin-dependent kinase kinases.