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Aims: Cardiovascular disease, primarily coronary artery disease (CAD), is the leading cause of mortality worldwide. Accurate diagnosis of CAD often requires pre-test probability (PTP) estimation, traditionally performed using scoring systems like the Diamond-Forrester (DF) and European Society of Cardiology (ESC) models. However, the applicability of such models in specific populations may vary. This study compares the performance of DF and PTP scores in the Brazilian context, using coronary computed tomography angiography (CCTA) as a reference standard. Methods and results: PTP for obstructive CAD was calculated using DF and ESC scores in 409 symptomatic patients without known CAD who underwent CCTA between 2019 and 2022. Predicted PTP was compared with actual CAD prevalence. DF overestimated CAD prevalence across age and symptom categories, while ESC showed better alignment with actual prevalence. Conclusion: Our study confirms that the ESC PTP model is more appropriate than the DF model for determining PTP in the Brazilian population.
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OBJECTIVES: Infant growth is recognized to vary over the short term, with periods of greater and lesser linear growth velocity. Our objectives were to (1) examine the potential differences in overall growth profiles between children who experienced cumulative growth faltering in the first year of life consistent with that seen by many children living in poverty in low- and middle-income countries, versus children without growth faltering and (2) test whether biological factors were associated with the timing of magnitude of growth saltations. METHODS: Thrice-weekly measurements of length were recorded for n = 61 Peruvian infants (28 boys and 33 girls) enrolled from birth to 1 year. A total of 6040 measurements were analyzed. We tested for the evidence of saltatory growth and used hurdle models to test whether the timing and magnitude of saltations varied between children with greater or lesser growth faltering. RESULTS: There were no differences in the duration of stasis periods or magnitude of growth saltations between children who were stunted at 1 year old (N = 18) versus those who were not stunted (N = 43). Children who experienced greater declines in LAZ in the first year of life trended toward longer periods between saltations than those with less of a decline (14.5 days vs. 13.4 days, p = .0512). A 1-unit increase in mid upper arm circumference for age Z-score in the 21 days prior was associated with 35% greater odds of a saltation occurring (p < .001), and a 0.128 cm greater saltation (p < .001). CONCLUSIONS: After characterizing infant growth into periods of saltation and stasis, our results suggest that increases in weight preceded increases in length.
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Transtornos do Crescimento , Humanos , Peru , Lactente , Masculino , Feminino , Recém-Nascido , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Estatura , Desenvolvimento InfantilRESUMO
The analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals.
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DNA Antigo , Tétano , Humanos , Animais , Camundongos , Neurotoxinas , Filogenia , Clostridium , Chile , MamíferosRESUMO
PURPOSE: To report a case of bilateral retinal hemorrhages in a patient undergoing two separate endovascular interventions for bilateral cerebral aneurysms. METHODS: A comprehensive ophthalmic examination was performed after the patient underwent each of two separate endovascular interventions for bilateral cerebral aneurysms. Multimodal imaging including widefield pseudocolor fundus photography, optical coherence tomography, and widefield fluorescein angiography (FA) was obtained. A systemic workup including genetic testing and hypercoagulability studies was performed. RESULTS: Dilated fundus examination revealed new visually significant ipsilateral retinal hemorrhages after each endovascular procedure. FA showed evidence of a peripheral retinal microangiopathy present in both eyes before the patient underwent her second endovascular procedure. Systemic workup revealed persistently elevated serum anticardiolipin IgM antibody levels at >99th percentile. CONCLUSION: Retinal complications after endovascular intracranial interventions are uncommon. This patient who developed bilateral retinal complications was found to have persistently elevated anticardiolipin antibody levels, a risk factor for thrombosis. Patients who develop retinal complications after endovascular intracranial intervention may benefit from systemic workup for hypercoagulable conditions.
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BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.
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Anti-Infecciosos , COVID-19 , Infecções por Bactérias Gram-Negativas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Carbapenêmicos , Cefalosporinas , Chile/epidemiologia , Resistência Microbiana a Medicamentos , Farmacorresistência Bacteriana Múltipla , Fluoroquinolonas , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hospitais , Fatores de Risco , AdultoRESUMO
OBJECTIVE: To evaluate genetic evaluation practices in newborns with the most common birth defect, congenital heart defects (CHD), we determined the prevalence and the yield of genetic evaluation across time and across patient subtypes, before and after implementation of institutional genetic testing guidelines. STUDY DESIGN: This was a retrospective, cross-sectional study of 664 hospitalized newborns with CHD using multivariate analyses of genetic evaluation practices across time and patient subtypes. RESULTS: Genetic testing guidelines for hospitalized newborns with CHD were implemented in 2014, and subsequently genetic testing increased (40% in 2013 and 75% in 2018, OR 5.02, 95% CI 2.84-8.88, P < .001) as did medical geneticists' involvement (24% in 2013 and 64% in 2018, P < .001). In 2018, there was an increased use of chromosomal microarray (P < .001), gene panels (P = .016), and exome sequencing (P = .001). The testing yield was high (42%) and consistent across years and patient subtypes analyzed. Increased testing prevalence (P < .001) concomitant with consistent testing yield (P = .139) added an estimated 10 additional genetic diagnoses per year, reflecting a 29% increase. CONCLUSIONS: In patients with CHD, yield of genetic testing was high. After implementing guidelines, genetic testing increased significantly and shifted to newer sequence-based methods. Increased use of genetic testing identified more patients with clinically important results with potential to impact patient care.
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Testes Genéticos , Cardiopatias Congênitas , Humanos , Recém-Nascido , Estudos Retrospectivos , Estudos Transversais , Testes Genéticos/métodos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/epidemiologia , Análise em MicrossériesRESUMO
BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29). CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).
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Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Doença da Artéria CoronarianaRESUMO
OBJECTIVE: To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy. METHODS: We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention. RESULTS: There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; Pâ¯=â¯.33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (Pâ¯=â¯0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; Pâ¯=â¯.90) or sepsis rates (1% vs 2%; Pâ¯=â¯.60). CONCLUSION: We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications.
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Antibacterianos , Próstata , Masculino , Humanos , Antibacterianos/uso terapêutico , Próstata/patologia , Antibioticoprofilaxia/métodos , Reto , Biópsia/efeitos adversos , Biópsia/métodos , Biópsia Guiada por Imagem/métodosRESUMO
PURPOSE: Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML. METHODS: To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis. RESULTS: Training set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays. CONCLUSION: Inclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.
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Leucemia Mieloide Aguda , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Leucemia Mieloide Aguda/terapia , Prognóstico , Resultado do Tratamento , MutaçãoRESUMO
The Neotropical brown stink bug, Euschistus heros, is a major pest of soybean in South America. The importance of E. heros as a pest has grown significantly in recent times due to increases in its abundance and range, and the evolution of insecticide resistance. Recent work has begun to examine the genetic diversity, population structure, and genetic mechanisms of insecticide resistance in E. heros. However, to date, investigation of these topics has been hampered by a lack of genomic resources for this species. Here we address this need by assembling a high-quality draft genome for E. heros. We used a combination of short and long read sequencing to assemble an E. heros genome of 1.4 Gb comprising 906 contigs with a contig N50 of 3.5 MB. We leveraged this new genomic resource, in combination with genotyping by sequencing, to explore genetic diversity in populations of this species in Brazil and identify genetic loci in the genome which are under selection. Our genome-wide analyses, confirm that there are two populations of E. heros co-occurring in different geographical regions in Brazil, and that, in certain regions of the country these populations are hybridizing. We identify several regions of the genome as under selection, including markers associated with putative insecticide resistance genes. Taken together, the new genomic resources generated in this study will accelerate research into fundamental aspects of stinkbug biology and applied aspects relating to the sustainable control of a highly damaging crop pest.
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Heterópteros , Inseticidas , Animais , Estudo de Associação Genômica Ampla , Heterópteros/genética , Brasil , DemografiaRESUMO
OBJECTIVE: To investigate the association between early life exposures during the first 1000 days (conception to age 24 months) and aortic intima-media thickness (aIMT), an early indicator of cardiovascular disease (CVD) risk, in youths. STUDY DESIGN: The MEDLINE, Embase, Scopus, CINAHL, and Allied and Complementary Medicine databases were searched from inception to July 2021. Eligibility criteria included observational controlled studies in youths aged <20 years with risk factors/exposures during the first 1000 days and aIMT measurements (unadjusted mean ± SD). Outcome data were pooled using a random-effects meta-analysis. Meta-regression was used to investigate confounders. RESULTS: A total of 8657 articles were identified, of which 34 were included in our meta-analysis. The age of participants ranged from 22.9 weeks gestation in utero to 10.9 years. In the meta-analysis (n = 1220 cases, n = 1997 controls), the following factors were associated with greater aIMT: small for gestational age (SGA) status (14 studies, mean difference, 0.082 mm; 95% CI, 0.051-0.112; P < .001; I2 = 97%), intrauterine growth restriction (6 studies; mean difference, 0.198 mm, 95% CI, 0.088-0.309; P < .001; I2 = 97%), preeclampsia (2 studies; mean difference, 0.038 mm; 95% CI, 0.024-0.051; P < .001; I2 = 38%), and large for gestational age (LGA) status (3 studies; mean difference, 0.089 mm; 95% CI, 0.043-0.0136; P < .001; I2 = 93%). In meta-regression, older age (P < .001), higher prevalence of maternal smoking (P = .04), and SGA (P < .001) were associated with greater difference in aIMT in preterm participants compared with controls. Limitations included the high heterogeneity present in most meta-analyses and the scope of our meta-regression. CONCLUSIONS: Adverse early life exposures are associated with greater aIMT in youths, consistent with an increased risk for CVD later in life. Further research is needed to determine whether intervention and preventive strategies deliver clinical benefits to improve future cardiovascular health.
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Doenças Cardiovasculares , Espessura Intima-Media Carotídea , Recém-Nascido , Gravidez , Feminino , Lactente , Adolescente , Humanos , Criança , Idade Gestacional , Retardo do Crescimento Fetal , Aorta/diagnóstico por imagem , Feto , Doenças Cardiovasculares/epidemiologiaRESUMO
PURPOSE: Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy. PATIENTS AND METHODS: Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria. RESULTS: One hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF. CONCLUSION: Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.
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Fator Estimulador de Colônias de Granulócitos e Macrófagos , Neuroblastoma , Criança , Humanos , Adulto , Intervalo Livre de Progressão , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Irinotecano/uso terapêutico , Temozolomida/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neuroblastoma/patologiaRESUMO
Molecular phenotypes induced by environmental stimuli can be transmitted to offspring through epigenetic inheritance. Using transcriptome profiling, we show that the adaptation of Helicoverpa armigera larvae to soybean peptidase inhibitors (SPIs) is associated with large-scale gene expression changes including the upregulation of genes encoding serine peptidases in the digestive system. Furthermore, approximately 60% of the gene expression changes induced by SPIs persisted in the next generation of larvae fed on SPI-free diets including genes encoding regulatory, oxidoreductase, and protease functions. To investigate the role of epigenetic mechanisms in regulating SPI adaptation, the methylome of the digestive system of first-generation larvae (fed on a diet with and without SPIs) and of the progeny of larvae exposed to SPIs were characterized. A comparative analysis between RNA-seq and Methyl-seq data did not show a direct relationship between differentially methylated and differentially expressed genes, while trypsin and chymotrypsin genes were unmethylated in all treatments. Rather, DNA methylation potential epialleles were associated with transcriptional and translational controls; these may play a regulatory role in the adaptation of H. armigera to SPIs. Altogether, our findings provided insight into the mechanisms of insect adaptation to plant antiherbivore defense proteins and illustrated how large-scale transcriptional reprograming of insect genes can be transmitted across generations.
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Glycine max , Mariposas , Animais , Glycine max/genética , Glycine max/metabolismo , Inibidores de Proteases/farmacologia , Regulação para Cima , Serina Proteases/metabolismo , Mariposas/genética , Mariposas/metabolismo , Quimotripsina/genética , Quimotripsina/metabolismo , Tripsina/metabolismo , Larva/genética , Larva/metabolismo , Serina/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: The COVID-19 pandemic accelerated virtual residency interview adoption. The impact of virtual interviews on program directors' (PD) National Residency Matching Program (NRMP) Match satisfaction, their future interview plans, and their perceptions about virtual interviews' influence on bias are unknown. We report the results of a survey of family medicine (FM) PDs about these topics after mandatory virtual interviews in 2020-2021. METHODS: A national survey of all FM PDs was conducted in April 2021 (n=619). The response rate was 46.37% (n=287). Questions asked whether PDs conducted virtual interviews, as well as PDs' general perceptions of virtual interviews' impact on administrative burden, diversity and bias; PD's ability to communicate program culture and assess applicants' alignment with program values; PD's satisfaction with Match results; and plans for interview structure postpandemic. RESULTS: Two hundred forty-four (93.1%) respondents performed only virtual interviews; 83.9% (n=220) conducting virtual interviews were satisfied with Match results, with no difference between programs with all virtual interviews vs others (OR 1.2, P=.994). PDs who communicated program values and involved residents in virtual interviews experienced higher Match satisfaction (OR 7.6, P<.001; OR 4.21, P=.001). PDs concerned about virtual interviews increasing bias against minorities before 2020 were still concerned after (OR 8.81, P<.001) and had lower Match satisfaction (OR 0.24, P=.001). CONCLUSIONS: Most FM PDs conducted entirely virtual interviews in 2020 and were satisfied with the Match. Interview processes including residents and conveying residency culture increased Match satisfaction. PDs are concerned about bias in virtual interviews, but more investigation about bias is needed.
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COVID-19 , Internato e Residência , Humanos , Viés Implícito , Pandemias , Inquéritos e QuestionáriosRESUMO
Purpose: To evaluate the reproducibility of magnitude of postoperative IOL rotation following implantation of a toric intraocular lens (IOL) with modified haptics, in comparison with a Proof-of-Concept (POC) study of prototype IOLs featuring the same haptic design. Patients and Methods: A post-market, prospective, multicenter, single-arm, open-label clinical study was conducted. TECNIS Toric II IOL (Johnson & Johnson Vision, Irvine, CA, USA, Models ZCU150 to 600) were implanted in 125 subjects and evaluated at 1-day and 1-week postoperatively. An objective photographic method was used to determine postoperative IOL rotation. Uncorrected distance visual acuity (UCDVA), postoperative astigmatism, and surgeon satisfaction were also assessed. Rotation data were compared to the POC study in which two prototype non-toric monofocal IOLs, one with the same haptic design as Model ZCU, were studied. Results: Mean absolute rotation was 0.82° ± 1.0° and 0.84° ± 0.92°at 1-day and 1-week visits, respectively. The percentage of eyes with ≤5° of absolute rotation was 98.9% and 99.5% at the 1-day and 1-week visits, respectively. The magnitude of rotation was similar to the POC study prototype IOLs. At 1-week, mean monocular UCDVA was 0.026 ± 0.135 (~20/21) logMAR and mean residual manifest refractive cylinder was 0.30 D ± 0.35 D. The mean signed axis difference (postoperative minus operative) of the TECNIS Toric II IOL was 0.23° ± 1.27° at 1-day and -0.07° ± 1.25° at 1-week, indicating a clockwise drift. At 1-week, surgeons were very satisfied or satisfied with overall clinical outcomes and rotational stability in 98% of implanted eyes. Conclusion: The TECNIS Toric II IOL, with frosted, squared haptics, demonstrated low magnitude of postoperative IOL rotation, excellent uncorrected distance vision, and minimal residual astigmatism. The POC study design was supported, demonstrating that prototype non-toric monofocal IOLs can predict clinical performance of toric IOLs with the same haptic design.
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An esophagopleural fistula (EPF) is a rare condition. EPFs are typically of spontaneous, iatrogenic, or neoplastic origin. A 50-year-old man with hepatitis C and alcoholic cirrhosis presented with a history of recurrent variceal hemorrhage requiring esophageal banding, Minnesota tube placement, and a transjugular intrahepatic portosystemic shunt. His hospital course after esophageal perforation and EPF was complicated by acute respiratory failure and empyema, necessitating intubation and thoracostomy tube placement. To the best of our knowledge, this is the first reported case of EPF secondary to Minnesota tube placement. The EPF completely healed after endoscopic repair.
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Eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) can cause fatal encephalitis in humans and equids. Some MAbs to the E1 glycoprotein are known to be cross-reactive, weakly neutralizing in vitro but can protect from disease in animal models. We investigated the mechanism of neutralization of VEEV infection by the broadly cross-reactive E1-specific MAb 1A4B-6. 1A4B-6 protected 3-week-old Swiss Webster mice prophylactically from lethal VEEV challenge. Likewise, 1A4B-6 inhibited virus growth in vitro at a pre-attachment step after virions were incubated at 37 °C and inhibited virus-mediated cell fusion. Amino acid residue N100 in the fusion loop of E1 protein was identified as critical for binding. The potential to elicit broadly cross-reactive MAbs with limited virus neutralizing activity in vitro but that can inhibit virus entry and protect animals from infection merits further exploration for vaccine and therapeutic developmental research.
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Anticorpos Antivirais/imunologia , Vírus da Encefalite Equina Venezuelana/imunologia , Vírus da Encefalite Equina Venezuelana/metabolismo , Encefalomielite Equina Venezuelana/imunologia , Encefalomielite Equina Venezuelana/virologia , Proteínas do Envelope Viral/imunologia , Replicação Viral/efeitos dos fármacos , Alphavirus/imunologia , Infecções por Alphavirus/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Linhagem Celular , Chlorocebus aethiops , Reações Cruzadas , Encefalomielite Equina Venezuelana/terapia , Glicoproteínas/imunologia , Imunoterapia , Camundongos , Ligação Proteica , Células Vero , Proteínas do Envelope Viral/metabolismo , Vírion/imunologia , Vírion/metabolismoRESUMO
Myocardial perfusion imaging (MPI) plays an important role in patients with suspected and documented coronary artery disease (CAD). Machine Learning (ML) algorithms have been developed for many medical applications with excellent performance. This study used ML algorithms to discern normal and abnormal gated Single Photon Emission Computed Tomography (SPECT) images. We analyzed one thousand and seven polar maps from a database of patients referred to a university hospital for clinically indicated MPI between January 2016 and December 2018. These studies were reported and evaluated by two different expert readers. The image features were extracted from a specific type of polar map segmentation based on horizontal and vertical slices. A senior expert reading was the comparator (gold standard). We used cross-validation to divide the dataset into training and testing subsets, using data augmentation in the training set, and evaluated 04 ML models. All models had accuracy >90% and area under the receiver operating characteristics curve (AUC) >0.80 except for Adaptive Boosting (AUC = 0.77), while all precision and sensitivity obtained were >96 and 92%, respectively. Random Forest had the best performance (AUC: 0.853; accuracy: 0,938; precision: 0.968; sensitivity: 0.963). ML algorithms performed very well in image classification. These models were capable of distinguishing polar maps remarkably into normal and abnormal.
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Hirschsprung disease (HD) is a congenital bowel innervation disorder characterized by the absence of ganglion cells in the neural plexus of the colorectal wall. Variant HD describes a heterogeneous group of intestinal innervation disorders in which clinical presentation resembles HD despite the presence of ganglion cells seen in rectal biopsies. We present the first reported case of a rare variant HD, hypoganglionosis isolated in the anorectal canal, diagnosed in an adult who presented with a long history of constipation and treated with proctosigmoidectomy with coloanal anastomosis. Histopathology showed rare ganglion cells isolated in the anorectal canal.