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1.
Invest Ophthalmol Vis Sci ; 65(3): 3, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441889

RESUMO

Purpose: To assess the degree to which quantitative foveal structural measurements account for variation in best-corrected visual acuity (BCVA) in human albinism. Methods: BCVA was measured and spectral domain optical coherence tomography (SD-OCT) images were acquired for 74 individuals with albinism. Categorical foveal hypoplasia grades were assessed using the Leicester Grading System for Foveal Hypoplasia. Foveal anatomical specialization (foveal versus parafoveal value) was quantified for inner retinal layer (IRL) thickness, outer segment (OS) length, and outer nuclear layer (ONL) thickness. These metrics, participant sex, and age were used to build a multiple linear regression of BCVA. This combined linear model's predictive properties were compared to those of categorical foveal hypoplasia grading. Results: The cohort included three participants with type 1a foveal hypoplasia, 23 participants with type 1b, 33 with type 2, ten with type 3, and five with type 4. BCVA ranged from 0.08 to 1.00 logMAR (mean ± SD: 0.53 ± 0.21). IRL ratio, OS ratio, and ONL ratio were measured in all participants and decreased with increasing severity of foveal hypoplasia. The best-fit combined linear model included all three quantitative metrics and participant age expressed as a binary variable (divided into 0-18 years and 19 years or older; adjusted R2 = 0.500). This model predicted BCVA more accurately than a categorical foveal hypoplasia model (adjusted R2 = 0.352). Conclusions: A quantitative model of foveal specialization accounts for more variance in BCVA in albinism than categorical foveal hypoplasia grading. Other factors, such as optical aberrations and eye movements, may account for the remaining unexplained variance.


Assuntos
Albinismo , Fóvea Central , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Retina , Acuidade Visual , Movimentos Oculares
2.
Front Med (Lausanne) ; 10: 1006743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020121

RESUMO

It is well known that common variants in specific genes influence drug metabolism and response, but it is currently unknown what fraction of patients are given prescriptions over a lifetime that could be contraindicated by their pharmacogenomic profiles. To determine the clinical utility of pharmacogenomics over a lifetime in a general patient population, we sequenced the genomes of 300 deceased Marshfield Clinic patients linked to lifelong medical records. Genetic variants in 33 pharmacogenes were evaluated for their lifetime impact on drug prescribing using extensive electronic health records. Results show that 93% of the 300 deceased patients carried clinically relevant variants. Nearly 80% were prescribed approximately three medications on average that may have been impacted by these variants. Longitudinal data suggested that the optimal age for pharmacogenomic testing was prior to age 50, but the optimal age is greatly influenced by the stability of the population in the healthcare system. This study emphasizes the broad clinical impact of pharmacogenomic testing over a lifetime and demonstrates the potential application of genomic medicine in a general patient population for the advancement of precision medicine.

3.
PLoS One ; 18(8): e0281277, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37594978

RESUMO

Microbial communities in terrestrial geothermal systems often contain chemolithoautotrophs with well-characterized distributions and metabolic capabilities. However, the extent to which organic matter produced by these chemolithoautotrophs supports heterotrophs remains largely unknown. Here we compared the abundance and activity of peptidases and carbohydrate active enzymes (CAZymes) that are predicted to be extracellular identified in metagenomic assemblies from 63 springs in the Central American and the Andean convergent margin (Argentinian backarc of the Central Volcanic Zone), as well as the plume-influenced spreading center in Iceland. All assemblies contain two orders of magnitude more peptidases than CAZymes, suggesting that the microorganisms more often use proteins for their carbon and/or nitrogen acquisition instead of complex sugars. The CAZy families in highest abundance are GH23 and CBM50, and the most abundant peptidase families are M23 and C26, all four of which degrade peptidoglycan found in bacterial cells. This implies that the heterotrophic community relies on autochthonous dead cell biomass, rather than allochthonous plant matter, for organic material. Enzymes involved in the degradation of cyanobacterial- and algal-derived compounds are in lower abundance at every site, with volcanic sites having more enzymes degrading cyanobacterial compounds and non-volcanic sites having more enzymes degrading algal compounds. Activity assays showed that many of these enzyme classes are active in these samples. High temperature sites (> 80°C) had similar extracellular carbon-degrading enzymes regardless of their province, suggesting a less well-developed population of secondary consumers at these sites, possibly connected with the limited extent of the subsurface biosphere in these high temperature sites. We conclude that in < 80°C springs, chemolithoautotrophic production supports heterotrophs capable of degrading a wide range of organic compounds that do not vary by geological province, even though the taxonomic and respiratory repertoire of chemolithoautotrophs and heterotrophs differ greatly across these regions.

4.
J Med Imaging (Bellingham) ; 10(Suppl 1): S11920, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37234196

RESUMO

Purpose: In this work, we endeavor to investigate how texture information may contribute to the response of a blur measure (BM) with motivation rooted in mammography. This is vital as the interpretation of the BM is typically not evaluated with respect to texture present in an image. We are particularly concerned with lower scales of blur (≤1 mm) as this blur is least likely to be detected but can still have a detrimental effect on detectability of microcalcifications. Approach: Three sets of linear models, where BM response was modeled as a linear combination of texture information determined by texture measures (TMs), were constructed from three different datasets of equal-blur-level images; one of computer-generated mammogram-like clustered lumpy background (CLB) images and two image sets derived from the Brodatz texture images. The linear models were refined by removing those TMs that are not significantly non-zero across all three datasets for each BM. We use five levels of Gaussian blur to blur the CLB images and assess the ability of the BMs and TMs to separate the images based on blur level. Results: We found that many TMs used frequently in the reduced linear models, mimicked the structure of the BMs that they modeled. Surprisingly, while none of the BMs could separate the CLB images across all levels of blur, a group of TMs could. These TMs occurred infrequently in the reduced linear models meaning that they rely on different information compared with that used by the BMs. Conclusion: These results confirm our hypothesis that BMs can be influenced by texture information in an image. That a subset of TMs performed better than all BMs on the blur classification problem with the CLB images further shows that conventional BMs may not be the optimal tool for blur classification in mammogram images.

5.
Int J Mol Sci ; 24(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36982708

RESUMO

Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure (IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in TTC28, KIAA1731, ADAMTS5, OR2W3, OR10A6, SAXO2, KCTD18, CHCHD6, and UPK1A were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (PDC80). While missense mutations in TINAG, CHCHD6, GSTZ1, and SEMA4G were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (MPR80). The same coding SNP in CHCHD6 which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (p = 5.54 × 10-6) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have protective associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.


Assuntos
Glaucoma , Adesão à Medicação , Humanos , Glaucoma/tratamento farmacológico , Glaucoma/genética , Pressão Intraocular/genética , Progressão da Doença , Tamanho da Amostra , Estudos Retrospectivos , Glutationa Transferase
6.
Nat Commun ; 14(1): 1502, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932076

RESUMO

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies revealed increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of ß2-integrins on patient neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis.


Assuntos
Células Endoteliais , Vasculite , Quinases da Família src , Humanos , Dasatinibe , Células Endoteliais/metabolismo , Inflamação/metabolismo , Neutrófilos/metabolismo , Fosforilação , Quinases da Família src/genética , Quinases da Família src/metabolismo , Vasculite/genética
7.
Mar Drugs ; 21(2)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36827106

RESUMO

We have been very humbled by the decision of the Marine Drugs Editors to honor us with a Special Issue dedicated to our efforts over the past 50 years, as well as their invitation to write a guest editorial for this issue [...].

8.
Clin Transplant ; 37(4): e14904, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36594638

RESUMO

BACKGROUND: The new United Network for Organ Sharing (UNOS) heart allocation policy prioritizes temporary percutaneous over durable left ventricular assist devices (LVAD) as bridge to transplant. We sought to examine 1-year outcomes of heart transplant recipients bridged with Impella versus durable LVADs. METHODS: All primary adult orthotopic heart transplant recipients registered in UNOS between January 2016 and June 2021 were analyzed. Recipients were identified as being bridged with isolated durable or percutaneous LVAD at the time of transplant. Baseline characteristics were compared and 1-year survival was examined using the Kaplan Meier method and multivariable Cox proportional hazards regression. RESULTS: During our study period, heart transplant recipients bridged with LVADs were divided between 5422(94%) durable and 324(6%) percutaneous options. Impella-bridged recipients were more likely to be status 1A under the old allocation system (98% vs. 70%, p < .01) and status 2 or higher under the new allocation system (99% vs. 24%, p < .01). Impella-bridged recipients were less likely to be obese (27% vs. 42%, p < .01), have ischemic cardiomyopathy (27% vs. 34%, p < .01), and were more likely to be on inotropic agents at the time of transplant (68% vs. 6%, p < .01). One-year post-transplant survival was not significantly different between the two groups on univariable (HR .87, 95% CI .56-1.37) or multivariable analysis (aHR .63, 95% CI .37-1.07). CONCLUSIONS: Following the UNOS allocation policy change, Impella utilization has increased with no significant difference in 1-year survival compared to bridge with durable LVADs. Impella may be a reasonable alternative to durable LVADs in select patients.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Adulto , Humanos , Resultado do Tratamento , Sobrevivência de Enxerto , Insuficiência Cardíaca/cirurgia , Estudos Retrospectivos
9.
Tex Heart Inst J ; 50(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695735

RESUMO

BACKGROUND: Aortic valve replacement improves survival for patients with low-gradient aortic valve stenosis, but there is a paucity of data on postoperative quality of life for this population. METHODS: In a single-center retrospective analysis of 304 patients with severe aortic valve stenosis who underwent transcatheter aortic valve replacement, patients were divided into 4 groups based on mean pressure gradient, left ventricular ejection fraction, and stroke volume index. Using the Kansas City Cardiomyopathy Questionnaire-12, quality of life was assessed immediately before and 1 month after transcatheter aortic valve replacement. RESULTS: Most patients in the low-flow, low-gradient group were men; this group had higher relative rates of cardiovascular disease and type 2 diabetes than the paradoxical low-flow, low-gradient group; the normal-flow, low-gradient group; and the high-gradient group. All-cause mortality did not differ significantly among the groups at 1 month after surgery, and all groups experienced a significant improvement in quality-of-life scores after surgery. The mean improvement was 27 points in the low-flow, low-gradient group, 25 points in the paradoxical low-flow, low-gradient group, 30 points in the normal-flow, low-gradient group, and 30 points in the high-gradient group (all P < .001). CONCLUSION: Quality of life improves significantly across all subgroups of aortic valve stenosis after trans-catheter aortic valve replacement, regardless of flow characteristics or aortic valve gradients.


Assuntos
Estenose da Valva Aórtica , Diabetes Mellitus Tipo 2 , Substituição da Valva Aórtica Transcateter , Masculino , Humanos , Feminino , Substituição da Valva Aórtica Transcateter/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Índice de Gravidade de Doença
10.
Am J Intellect Dev Disabil ; 128(1): 1-20, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36548377

RESUMO

Variation in the FMR1 gene may affect aspects of cognition, such as executive function and memory. Environmental factors, such as stress, may also negatively impact cognitive functioning. Participants included 1,053 mothers of children with and without developmental disabilities. Participants completed self-report measures of executive function, memory, and stress (i.e., life events, parenting status), and provided DNA to determine CGG repeat length (ranging from 7 to 192 CGGs). Stress exposure significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems. Cubic CGG effects independently predicted executive function and memory difficulties, suggesting effects of both genetic variation and environmental stress exposure on cognitive functioning.


Assuntos
Cognição , Proteína do X Frágil da Deficiência Intelectual , Mães , Estresse Psicológico , Expansão das Repetições de Trinucleotídeos , Criança , Feminino , Humanos , Função Executiva , Proteína do X Frágil da Deficiência Intelectual/genética , Mães/psicologia , Autorrelato , Estresse Psicológico/genética
12.
J Med Imaging (Bellingham) ; 9(Suppl 1): S12209, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36034746

RESUMO

Image processing has contributed greatly to the clinical applications of medical imaging. Many of the major developments have been stimulated by and reported at the Image Processing (IP) conference held annually as part of the SPIE Medical Imaging meeting. The evolution, focus, and impact of the IP conference is reviewed.

13.
Pract Radiat Oncol ; 12(2): 120-124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34649005

RESUMO

Previous studies have demonstrated that patients can be identified from 3-dimensional (3D) reconstructions of computed tomography (CT) or magnetic resonance imaging data of the brain or head and neck. This presents a privacy and security concern for scan data released to public data sets. It is unknown whether thermoplastic immobilization masks used for treatment planning in radiation therapy are sufficient to prevent facial recognition. Our study sought to evaluate whether patients with an immobilization mask could be identified on 3D reconstructions of scan data. Our study reconstructed 3D images from simulation CT (SIM-CT) scans of 35 patients and compared these to original patient photographs to test if the thermoplastic mask obfuscated facial features. Blind review from 4 facial recognition algorithms and a human (radiation oncologist) was evaluated for the ability to match 3D reconstructions of patients scans to patient images. The matching procedure was repeated against an expanded testing data set of the 35 patient photographs plus 13,233 facial photographs from the "Labeled Faces in the Wild" data set (13,268 photographs in total). Facial recognition algorithms were able to match a maximum of 83% (range, 60%-83%) of patients to the corresponding images. Radiation Oncologist blinded review correctly matched 80% of patients to the corresponding images. Ethnicity and facial hair were the most common reasons for patient mismatch. In the expanded testing data set, algorithms were also able to match a maximum of 83% (range, 57%-83%) of patients. The majority of patients were able to be identified through computer algorithm or human review even under a SIM-CT mask. These results suggest there is a potential privacy and security concern when SIM-CT data are released to publicly available data sets.


Assuntos
Privacidade , Tomografia Computadorizada por Raios X , Algoritmos , Cabeça , Humanos , Imageamento Tridimensional/métodos , Imobilização/métodos , Pescoço , Tomografia Computadorizada por Raios X/métodos
14.
J Thorac Cardiovasc Surg ; 163(6): 2155-2162.e4, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676757

RESUMO

OBJECTIVE: The importance of nontechnical skills in surgery is widely recognized. We demonstrate the feasibility of administering and assessing the results of a formal Non-Technical Skills in Surgery (NOTSS) curriculum to cardiothoracic surgery residents. METHODS: Eight cardiothoracic surgery residents participated in the NOTSS curriculum. They were assessed on their cognitive (situation awareness, decision-making) and social (communication and teamwork, leadership) skills based on simulated vignettes. The residents underwent pretraining NOTSS assessments followed by self-administered confidence ratings regarding the 4 skills. Subsequently, a formal NOTSS lecture was delivered and additional readings from the NOTSS textbook was assigned. A month later, the residents returned for post-training NOTSS assessments and self-administered confidence ratings. Changes across days (or within-day before vs after curriculum) were assessed using Wilcoxon signed rank test. RESULTS: There was a significant improvement in the overall NOTSS assessment score (P = .01) as well as in the individual categories (situation awareness, P = .02; decision-making, P = .02; communication and teamwork, P = .01; leadership, P = .02). There was also an increase in resident self-perception of improvement on the post-training day (P = .01). CONCLUSIONS: We have developed a simulation-based NOTSS curriculum in cardiothoracic surgery that can be formally integrated into the current residency education. This pilot study indicates the feasibility of reproducible assessments by course educators and self-assessments by participating residents in nontechnical skills competencies.


Assuntos
Cirurgia Geral , Internato e Residência , Treinamento por Simulação , Competência Clínica , Currículo , Educação de Pós-Graduação em Medicina , Cirurgia Geral/educação , Humanos , Projetos Piloto , Treinamento por Simulação/métodos
15.
Mov Disord ; 36(10): 2378-2386, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34117786

RESUMO

BACKGROUND: Premutation-sized (55-200) CGG repeat expansions in the FMR1 gene cause fragile X-associated tremor/ataxia syndrome (FXTAS). Most studies of premutation carriers utilized reverse ascertainment to identify patients, leading to a selection bias for larger repeats. As shorter CGG premutation repeats are common in the population, understanding their impact on health outcomes has a potentially large public health footprint. OBJECTIVE: The study's objective was to compare an unselected group of premutation carriers (n = 35, 55-101 CGG repeats) with matched controls (n = 61, 29-39 CGG repeats) with respect to FXTAS-type signs using structured neurological assessments. METHODS: Three neurologists independently rated signs, using an adapted version of the FXTAS Rating Scale (Leehey MA, Berry-Kravis E, Goetz CG, et al. FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology. 2008). This was a double-blind study, as genetic status (premutation vs. control) was known neither by the participants nor by any of the neurologists. Analyses controlled potentially confounding comorbid conditions in the electronic health record (eg, osteoarthritis and stroke) and probed the association of age with signs. RESULTS: Although there was no overall difference between carriers and controls, among individuals without any potentially confounding comorbid diagnoses, there was a statistically significant age-associated elevation in FXTAS-type signs in premutation carriers compared to controls. CONCLUSIONS: Among those who do not have other comorbid diagnoses, women who have CGG repeats at the lower end of the premutation range may be at greater risk for ataxia and parkinsonism than their age peers, although their overall risk of developing such clinical features is low. This study should provide reassurance to those who share characteristics with the present cohort. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Heterozigoto , Ataxia/genética , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Humanos , Tremor/genética , Expansão das Repetições de Trinucleotídeos
16.
Brachytherapy ; 20(5): 1053-1061, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34088594

RESUMO

PURPOSE: To provide an assessment of safety regarding high-dose-rate after-loading brachytherapy (HDR-BT) based on adverse events reported to the OpenFDA, an open access database maintained by the United States Food and Drug Administration (FDA). METHODS: OpenFDA was queried for HDR-BT events between 1993 and 2019. A brachytherapist categorized adverse events (AEs) based on disease site, applicator, manufacturer, event type, dosimetry impact, and outcomes. Important findings are summarized. RESULTS: 372 AEs were reported between 1993 and 2019, with a downwards trend after 2014. Nearly half of AEs (48.9%) were caused by a device malfunction, and 27.4% resulted in patient injury. Breast (49.2%) and Gyn (23.7%) were the most common disease sites of AEs. Applicator breaks cause the majority of AEs (64.2%) and breast balloon implants were the most common applicator to malfunction (38.7%). User error contributed to only 16.7% of events. 11.0% of events required repair of the afterloader. There were no reported staff injuries or patient deaths from an AE, however 24.7% of patients received resultant incorrect radiation dose, 16.4% required additional procedures to rectify the AE, and 3.0% resulted in unintended radiation to staff. CONCLUSION: The OpenFDA database has shown a decreasing trend in AEs since 2014 for HDR-BT. Most AEs are not caused by user error and do not cause patient injury or incorrect radiation dose. Investigation into methods to prevent failures and improve applicators such as the breast balloon could improve safety. These results support the continued use of HDR-BT as a safe treatment modality for cancer.


Assuntos
Braquiterapia , Braquiterapia/métodos , Humanos , Radiometria , Dosagem Radioterapêutica , Estados Unidos/epidemiologia , United States Food and Drug Administration
17.
J Card Surg ; 36(8): 2722-2728, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34047391

RESUMO

OBJECTIVE: Unrecognized left ventricular thrombi (LVT) can have devastating clinical implications and precludes patients with end-stage heart failure from undergoing left ventricular assist device (LVAD) implantation without cardiopulmonary bypass assistance. We assessed the reliability of an echocardiogram to diagnose LVT in patients with end-stage heart disease who underwent LVAD implantation. METHODS: A single-center retrospective study evaluated 232 consecutive adult patients requiring implantation of durable LVADs between 2005 and 2019. The validity of preoperative transthoracic echocardiogram (TTE) and intraoperative transesophageal echocardiogram (TEE) for diagnosing LVT was compared to direct inspection at the time of LVAD implantation. RESULTS: There were 232 patients that underwent LVAD implantation, with 226 patients (97%) receiving a preoperative TTE. Of those 226 patients, 32 patients (14%) received ultrasound enhancing agents (UEA). Intraoperative TEE images were available in 195 patients (84%). The sensitivity of TTE without UEA was 22% and specificity was 90% for detecting LVT, compared to 50% and 86%, respectively, for TTE with UEA. For intraoperative TEE, the sensitivity and specificity were 46% and 96%, respectively. The false omission rate ranged from 4% to 8% for all modalities of echocardiography. CONCLUSION: Among patients undergoing LVAD implantation, preoperative TTE and intraoperative TEE had poor sensitivity for LVT detection. Up to 8% of echocardiograms were incorrectly concluded to be negative for LVT on surgical validation. The low sensitivity and positive predictive value for diagnosing LVT suggest that echocardiography has limited reliability in this cohort of patients who are at high risk of LVT formation and its subsequent complications.


Assuntos
Coração Auxiliar , Trombose , Adulto , Ecocardiografia , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Trombose/diagnóstico por imagem
18.
NPJ Digit Med ; 4(1): 70, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850243

RESUMO

Chronic Kidney Disease (CKD) represents a slowly progressive disorder that is typically silent until late stages, but early intervention can significantly delay its progression. We designed a portable and scalable electronic CKD phenotype to facilitate early disease recognition and empower large-scale observational and genetic studies of kidney traits. The algorithm uses a combination of rule-based and machine-learning methods to automatically place patients on the staging grid of albuminuria by glomerular filtration rate ("A-by-G" grid). We manually validated the algorithm by 451 chart reviews across three medical systems, demonstrating overall positive predictive value of 95% for CKD cases and 97% for healthy controls. Independent case-control validation using 2350 patient records demonstrated diagnostic specificity of 97% and sensitivity of 87%. Application of the phenotype to 1.3 million patients demonstrated that over 80% of CKD cases are undetected using ICD codes alone. We also demonstrated several large-scale applications of the phenotype, including identifying stage-specific kidney disease comorbidities, in silico estimation of kidney trait heritability in thousands of pedigrees reconstructed from medical records, and biobank-based multicenter genome-wide and phenome-wide association studies.

19.
Proc Natl Acad Sci U S A ; 117(39): 24165-24172, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32929019

RESUMO

The Convention on Biological Diversity, and the Nagoya Protocol in particular, provide a framework for the fair and equitable sharing of benefits arising from the utilization of biological resources and traditional knowledge, and ultimately aim to promote capacity-building in the developing world. However, measuring capacity-building is a challenging task due to its intangible nature. By compiling and analyzing a database of scientific peer-reviewed publications over a period of 50 y (1965 to 2015), we investigated capacity-building in global marine natural product discovery. We used publication and authorship metrics to assess how the capacity to become scientifically proficient, prolific, and independent has changed in bioprospecting countries. Our results show that marine bioprospecting is a dynamically growing field of research with continuously increasing numbers of participating countries, publications, and scientists. Yet despite longstanding efforts to promote equitability and scientific independence, not all countries have similarly increased their capacity to explore marine biodiversity within their national jurisdiction areas. Although developing countries show an increasing trend in the number of publications, a few developed countries still account for almost one-half of all publications in the field. Multiple lines of evidence suggest that economic capacity affects how well countries with species-rich marine ecosystems can scientifically explore those resources. Overall, the capacity-building data analyzed here provides a timely contribution to the ongoing international debate about access to and benefit-sharing of biological resources for countries exploring biodiversity within and outside their national jurisdiction areas.


Assuntos
Organismos Aquáticos , Biodiversidade , Produtos Biológicos , Bioprospecção/história , Cooperação Internacional , História do Século XX , História do Século XXI
20.
J Vasc Interv Radiol ; 31(8): 1342-1347.e1, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32680683

RESUMO

Development of a pseudoaneurysm of the ascending aorta is an uncommon complication of aortic surgery. Several nonsurgical techniques are available for treatment of ascending aortic pseudoaneurysms (AAPs). This report outlines a single-center retrospective experience with 14 nonsurgical procedures for treatment of AAPs in 10 patients. Modified stent grafts, septal defect occlusion devices, coil embolics, and liquid embolics were deployed by transthoracic and endovascular approaches. Complete stasis of the AAP was achieved in 7 of 10 patients (70%). Mean postprocedural recoveries occurred within 3.5 days. Nonsurgical techniques for repair of AAPs offer a comparatively safe and effective alternative to open surgical repair.


Assuntos
Falso Aneurisma/terapia , Aneurisma Aórtico/terapia , Implante de Prótese Vascular , Embolização Terapêutica , Procedimentos Endovasculares , Adulto , Idoso , Idoso de 80 Anos ou mais , Falso Aneurisma/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
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