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1.
J Manag Care Spec Pharm ; 26(4): 361-366, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223597

RESUMO

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fluetsch, Rind, and Pearson are employed by ICER. Lin reports support from ICER during work on this economic model and grants from Mount Zion Health Fund, National Institutes of Health (National Cancer Institute and National Heart, Lung, and Blood Institute), and the Tobacco-Related Diseases Research Program, unrelated to this work. Walton reports support from ICER for work on this economic model and unrelated consulting fees from Baxter.

2.
Can J Cardiol ; 36(3): 384-395, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32145866

RESUMO

Light-chain (AL) amyloidosis is a systemic syndrome characterized by progressive organ dysfunction leading to organ failure and death. The heart is the most commonly involved organ and the leading determinant of short- and long-term survival. Pathogenic free light chains, fragments of intact immunoglobulins, are the amyloidogenic proteins and are secreted by clonal bone marrow plasma cells. The goal of therapy is to cut off the supply of these light chains to allow organ recovery. Therapies for AL amyloidosis are based on therapies used to treat multiple myeloma, which is a more common plasma cell disorder. However, because patients with AL amyloidosis have organ dysfunction, including multiorgan involvement, they generally have poor treatment tolerance and increased treatment toxicity. Unfortunately, the consequences of toxicity and difficulty in tolerating treatment may result in a fatal outcome. Therefore, treatment should balance the goal of achieving a rapid and meaningful reduction in the circulating light chains while maximizing patient safety. This approach is best achieved by a multidisciplinary approach involving related medical disciplines. This review describes the challenges of managing patients with AL amyloidosis and provides a guide for physicians with a specific focus on cardiac management. We address the role of autologous stem cell transplantation vs standard-intensity therapies in a risk-adapted approach and discuss the management of commonly encountered toxicities. Guidance on response assessment, including organ response, is provided. With expansion in treatment options, we anticipate continuous improvement in outcome for this disease. Nonetheless, early diagnosis remains the best approach to improve disease burden and outcome.

4.
Eur J Heart Fail ; 22(3): 489-498, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31908127

RESUMO

AIMS: Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. METHODS AND RESULTS: Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n = 163), patients with MR-HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P < 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. CONCLUSIONS: Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

5.
Mayo Clin Proc ; 95(1): 69-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31902431

RESUMO

OBJECTIVE: To assess the impact of stroke volume index (SVI) and left ventricular ejection fraction (LVEF) on prognosis in patients with severe aortic stenosis, comparing those undergoing transcatheter aortic valve replacement (TAVR) and those with surgical AVR (SAVR). PATIENTS AND METHODS: A total of 742 patients from the CoreValve US Pivotal High-Risk Trial randomized to TAVR (n=389) or SAVR (n=353) from February 2011 to September 2012 were stratified by an SVI of 35 mL/m2 and LVEF of 50% for comparing all-cause mortality at 1 year. RESULTS: The prevalence of an SVI of less than 35 mL/m2 in patients who underwent TAVR and SAVR was 35.8% (125 of 349) and 31.3% (96 of 307), respectively; LVEF of less than 50% was present in 18.1% (63 of 348) and 19.6% (60 of 306), respectively. Among patients with an SVI of less than 35 mL/m2, 1-year mortality was similar between patients with TAVR and SAVR (16.3% vs 22.2%; P=.25). However, in those with an SVI of 35 mL/m2 or greater, 1-year mortality was lower in those with TAVR than SAVR (10.3% vs 17.3%; P=.03). In patients with an LVEF of less than 50%, mortality was not affected by AVR approach (P>.05). In patients with an LVEF of 50% or higher, TAVR was associated with lower mortality than SAVR when SVI was preserved (9.8% vs 18.6%; P=.01). Mortality was not affected by SVI within the same AVR approach when LVEF was 50% or higher. CONCLUSION: In patients with severe aortic stenosis at high risk, there is a significant interaction between AVR approach and the status of SVI and LVEF. When LVEF or SVI was reduced, prognosis was similar regardless of AVR approach. In those with preserved LVEF or SVI, TAVR was associated with a better prognosis than SAVR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01240902.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Volume Sistólico , Substituição da Valva Aórtica Transcateter , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Correlação de Dados , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Substituição da Valva Aórtica Transcateter/estatística & dados numéricos , Resultado do Tratamento
7.
Hepatology ; 71(1): 334-345, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31342529

RESUMO

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end-stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice-based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

8.
Med Care ; 58(1): 45-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31821245

RESUMO

BACKGROUND: Limited English proficiency is associated with decreased access to ambulatory care, however, it is unclear if this disparity leads to increased use of emergency departments (EDs) for low severity ambulatory care sensitive conditions (ACSCs). OBJECTIVE: We sought to determine the association between the patient's preferred language and hospital utilization for ACSCs. RESEARCH DESIGN: We conducted a retrospective cohort study of all ED visits in New Jersey in 2013 and 2014. The primary outcome was hospital admission for acute ACSCs, chronic ACSCs, and fractures (a nonambulatory care sensitive control condition). Secondary outcomes included intensive care unit (ICU) utilization and length of stay. Mixed-effect regression models estimated the association between preferred language (English vs. non-English) and study outcomes, controlling for demographics, comorbidities, and hospital characteristics. RESULTS: We examined 201,351 ED visits for acute ACSCs, 251,193 visits for chronic ACSCs, and 148,428 visits for fractures, of which 13.5%, 11.1%, and 9.9%, respectively, were by non-English speakers. In adjusted analyses, non-English speakers were less likely to be admitted for acute ACSCs [-3.1%; 95% confidence interval (CI), -3.6% to -2.5%] and chronic ACSCs (-2.3%; 95% CI, -2.8% to -1.7%) but not fractures (0.4%; 95% CI, -0.2% to 1.0%). Among hospitalized patients, non-English speakers were less likely to receive ICU services but had no difference in length of stay. CONCLUSIONS: These findings suggest non-English-speaking patients may seek ED care for lower acuity ACSCs than English-speaking patients. Efforts to decrease preventable ED and increase access to ambulatory care use should consider the needs of non-English-speaking patients.

9.
J Cardiovasc Electrophysiol ; 31(1): 185-195, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31840870

RESUMO

BACKGROUND: The accurate separation of undifferentiated wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular wide complex tachycardia (SWCT) using conventional, manually-applied 12-lead electrocardiogram (ECG) interpretation methods is difficult. PURPOSE: We sought to devise a new WCT differentiation method that operates solely on automated measurements routinely provided by computerized ECG interpretation software. METHODS: In a two-part analysis, we developed and validated a logistic regression model (ie, VT Prediction Model) that utilizes routinely available computerized measurements derived from patients' paired WCT and baseline ECGs. RESULTS: The derivation cohort consisted of 601 paired WCT (273 VT, 328 SWCT) and baseline ECGs from 421 patients. The VT Prediction Model, composed of WCT QRS duration (ms) (P < .0001), QRS duration change (ms) (P < .0001), QRS axis change (°) (P < .0001) and T axis change (°) (P < .0001), yielded effective VT and SWCT differentiation (area under the curve [AUC]: 0.924; confidence interval [CI]: 0.903-0.944) for the derivation cohort. The validation cohort comprised 241 paired WCT (97 VT, 144 SWCT) and baseline ECGs from 177 patients. The VT Prediction Model's implementation on the validation cohort yielded effective WCT differentiation (AUC: 0.900; CI: 0.862-0.939) with overall accuracy, sensitivity, and specificity of 85.0%, 80.4%, and 88.2%, respectively. CONCLUSION: The VT Prediction Model is an example of how readily available ECG measurements may be used to distinguish VT and SWCT effectively. Further study is needed to develop and refine newer WCT differentiation approaches that utilize computerized measurements provided by ECG interpretation software.

10.
Am J Med Genet A ; 182(2): 296-302, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846207

RESUMO

Haim-Munk syndrome (HMS) and Papillon-Lefevre syndrome (PLS) are phenotypic variants of palmoplantar keratoderma (PPK) with progressive early-onset periodontitis and dental caries. HMS and PLS have been associated with homozygous or compound heterozygous mutations in the lysosomal protease gene Cathepsin C (CTSC). There have been only a few documented cases of CTSC mutations in patients from South-East Asia. We report the clinical findings of two Cambodian brothers who presented with diffuse, demarcated PPK with transgrediens extending to the elbows and knees, as well as pachyonychia and dental caries. Arachnodactyly and periodontitis were also found in the older brother. Next-generation sequencing unveiled a homozygous missense variant in CTSC (NM_001814.5: c.1337AC: p.(Asp446Ala)) in both brothers. Both parents were heterozygous for the variant, while an unaffected older brother was homozygous for the wild-type allele. Our study adds to the spectrum of mutations and associated clinical presentations for this rare genodermatosis.

11.
Hepatology ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709572

RESUMO

We appreciate the letter by Koshy et al. We agree with the authors that blunted contractile response to stress is a pathophysiologically relevant criterion in the assessment for cirrhotic cardiomyopathy (CCM). We also agree that, unfortunately, the lack of a universal, precise definition of this criterion limits its utility in daily clinical practice, at this time.

13.
Dev Sci ; : e12908, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587470

RESUMO

Sources that contribute to variation in mathematical achievement include both numerical knowledge and general underlying cognitive processing abilities. The current study tested the benefits of tablet-based training games that targeted each of these areas for improving the mathematical knowledge of kindergarten-age children. We hypothesized that playing a number-based game targeting numerical magnitude knowledge would improve children's broader numerical skills. We also hypothesized that the benefits of playing a working memory (WM) game would transfer to children's numerical knowledge given its important underlying role in mathematics achievement. Kindergarteners from diverse backgrounds (n = 148; 52% girls; Mage  = 71.87 months) were randomly assigned to either play a number-based game, a WM game, or a control game on a tablet for 10 sessions. Structural equation modeling was used to model children's learning gains in mathematics and WM across time. Overall, our results suggest that playing the number game improved kindergarten children's numerical knowledge at the latent level, and these improvements remained stable as assessed 1 month later. However, children in the WM group did not improve their numerical knowledge compared to children in the control condition. Playing both the number game and WM game improved children's WM at the latent level. Importantly, the WM group continued to improve their WM for at least a month after playing the games. The results demonstrate that computerized games that target both domain-specific and domain-general skills can benefit a broad range of kindergarten-aged children.

14.
mSystems ; 4(5)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551401

RESUMO

To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs.

15.
Future Sci OA ; 5(8): FSO413, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31534781

RESUMO

Microphysiological systems play a pivotal role in progressing toward a global paradigm shift in drug development. Here, we designed a four-organ-chip interconnecting miniaturized human intestine, liver, brain and kidney equivalents. All four organ models were predifferentiated from induced pluripotent stem cells from the same healthy donor and integrated into the microphysiological system. The coculture of the four autologous tissue models in one common medium deprived of tissue specific growth factors was successful over 14-days. Although there were no added growth factors present in the coculture medium, the intestine, liver and neuronal model maintained defined marker expression. Only the renal model was overgrown by coexisting cells and did not further differentiate. This model platform will pave the way for autologous coculture cross-talk assays, disease induction and subsequent drug testing.

17.
Diagn Cytopathol ; 47(12): 1306-1309, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31400261

RESUMO

Intranodal palisaded myofibroblastoma is a rare lymph node mesenchymal neoplasm that most commonly arises in inguinal lymph nodes. There is limited data about cytologic features of this tumor and its diagnostic pitfalls. The combination of bland appearing spindle cells, fibrillary matrix, and hemosiderin pigments are the characteristic features of this neoplasm in cytologic specimens.

18.
Case Rep Pathol ; 2019: 8025103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380135

RESUMO

Dedifferentiated liposarcomas most commonly arise in the retroperitoneum, accounting for 10% of liposarcomas. Heterologous differentiation occurs in 5-10% of dedifferentiated liposarcomas; however, divergent osteosarcomatous differentiation is rare. We report a rare case of initial presentation of dedifferentiated liposarcoma with osteosarcomatous component as a colonic mass in a 72-year-old man. The tumor is mainly composed of bony trabeculae with intervening highly atypical cells and adjacent high-grade mesenchymal nonlipogenic tumor, as well as areas of well-differentiated liposarcoma. Immunohistochemical studies showed diffuse positivity for SATB2 in the atypical cells and fluorescence in situ hybridization revealed high-level amplification of MDM2 gene, supporting the diagnosis of well-differentiated and dedifferentiated liposarcoma with heterologous osteosarcomatous differentiation.

20.
Mol Biol Rep ; 46(5): 5089-5102, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364015

RESUMO

According to standing regulations animal tests are still state of the art for the evaluation of the sensitization potential of medical devices. The aim of our study was to develop an in vitro method that can be used for testing of extracts of medical devices. The novel MDA-ARE assay is a cell based reporter gene assay focused on the ARE-Nrf2 pathway, which is involved in the dermal sensitization process. Optimization of the reporter construct and the cell line resulted in an improvement of the detection limit and a reduction of the incubation time to 6 h, which lowers cytotoxic side effects of the extracts on the cells. Using the assay, 21 out of 22 pure chemicals were identified correctly as skin sensitizers or non-sensitizers. All sensitizers could be detected at far lower concentrations compared to the local lymph node assay, the state-of-the-art animal test. To evaluate the assay's suitability for the testing of medical devices, medical grade silicone containing 0.1% of known skin sensitizers was prepared as positive controls and extracts of these positive controls were tested in comparison to extracts from pure silicone samples. All silicone samples were correctly and reproducibly identified as sensitizing or non-sensitizing demonstrating that the MDA-ARE assay is a sensitive and reliable tool for the detection of skin sensitizers in extracts of medical devices. The developed and validated test protocol was used for medical device extracts and showed its applicability for real samples and thus can contribute to reduce or even to replace the need for animal tests.


Assuntos
Equipamentos e Provisões/efeitos adversos , Hipersensibilidade/diagnóstico , Luciferases/metabolismo , Silicones/química , Linhagem Celular , Genes Reporter , Células HEK293 , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/metabolismo , Técnicas In Vitro , Limite de Detecção , Luciferases/genética , Modelos Biológicos , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais , Silicones/efeitos adversos
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