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1.
New Phytol ; 241(5): 2227-2242, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38151719

RESUMEN

The tomato (Solanum lycopersicum) ripening inhibitor (rin) mutation is known to completely repress fruit ripening. The heterozygous (RIN/rin) fruits have extended shelf life, ripen normally, but have inferior taste/flavour. To address this, we used genome editing to generate newer alleles of RIN (rinCR ) by targeting the K-domain. Unlike previously reported CRISPR alleles, the rinCR alleles displayed delayed onset of ripening, suggesting that the mutated K-domain represses the onset of ripening. The rinCR fruits had extended shelf life and accumulated carotenoids at an intermediate level between rin and progenitor line. Besides, the metabolites and hormonal levels in rinCR fruits were more akin to rin. To overcome the negative attributes of rin, we crossed the rinCR alleles with Nps1, a dominant-negative phototropin1 mutant, which enhances carotenoid levels in tomato fruits. The resulting Nps1/rinCR hybrids had extended shelf life and 4.4-7.1-fold higher carotenoid levels than the wild-type parent. The metabolome of Nps1/rinCR fruits revealed higher sucrose, malate, and volatiles associated with tomato taste and flavour. Notably, the boosted volatiles in Nps1/rinCR were only observed in fruits bearing the homozygous Nps1 mutation. The Nps1 introgression into tomato provides a promising strategy for developing cultivars with extended shelf life, improved taste, and flavour.


Asunto(s)
Carotenoides , Solanum lycopersicum , Carotenoides/metabolismo , Solanum lycopersicum/genética , Proteínas de Dominio MADS/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Gusto , Frutas/genética , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Etilenos/metabolismo
2.
Int J Equity Health ; 22(1): 240, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978389

RESUMEN

Social participation, also termed stakeholder voice, is an important component of health system governance. Increased interactions between the community and policy makers could facilitate a more responsive health system that targets the needs of the community better. Recently, the World Health Organization (WHO) published a handbook on social participation that identified five key themes for ministries of health to consider when engaging the input of the community. In this rapid systematic literature review, we aimed to identify quantitative and qualitative measures that have been used to assess aspects of social participation involving people and policy makers. We identified 172 measures from 48 studies from countries in all six WHO regions. These measures were categorized by all five themes from the handbook on social participation and these measures are linked to 27 concepts. This rapid review found that the focus of measures is largely on the existence of participation-be it by the general population or specific vulnerable groups-rather than on the quality of their participation. The measures in this inventory may be useful for ministries of health and other key stakeholders to use when developing methods to assess and encourage social participation in their context.


Asunto(s)
Programas de Gobierno , Participación Social , Humanos , Políticas , Personal Administrativo
3.
Indian J Plast Surg ; 56(2): 159-165, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37153338

RESUMEN

Background Soft tissue coverage of the distal foot and ankle region has been an area of debate due to the paucity of local flap options. To provide empirical evidence on the reliability of an underreported local alternative for foot and ankle defects, we aim to compare the lateral supramalleolar flap (LSMF) to the reverse sural flap (RSF). Methods During 2016-2019, 48 patients were divided randomly into two equal groups, LSMF and RSF groups respectively. The patients' demographic, surgical, and clinical outcome details were recorded and analyzed. Results Flap necrosis was found in five patients in the group treated with RSF and none in the LSMF group. The mean total number of stages in RSF group was significantly higher than in LSMF group ( p < 0.05). The mean operative time for patients in LSMF group was 85.8 ± 18.5 and 54.2 ± 11.2 in RSF group ( p < 0.05). Five patients in the RSF group needed additional procedures following flap complications. Nine patients in the LSMF group reported satisfaction outcomes to be "excellent," five patients reported "good" whereas, in the RSF group, 14 patients reported "excellent," 5 reported "good," 3 reported "fair," and 2 reported "poor" outcomes. Compared to the RSF (46.4 ± 4.3) group, the LSMF group had significantly better foot function indices (34.03 ± 3.9). Conclusion The lateral supramalleolar flap for foot and ankle defects offers better results, reduced complications as well a lesser number of stages and secondary procedures over the traditionally used reverse sural flap.

4.
Electrophoresis ; 43(5-6): 688-695, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34910828

RESUMEN

We present the implementation and demonstration of the Chebyshev pseudo-spectral method coupled with an adaptive mesh method for performing fast and highly accurate electrophoresis simulations. The Chebyshev pseudo-spectral method offers higher numerical accuracy than all other finite difference methods and is applicable for simulating all electrophoresis techniques in channels with open or closed boundaries. To improve the computational efficiency, we use a novel moving mesh scheme that clusters the grid points in the regions with poor numerical resolution. We demonstrate the application of the Chebyshev pseudo-spectral method on a moving mesh for simulating nonlinear electrophoretic processes through examples of isotachophoresis (ITP), isoelectric focusing (IEF), and electromigration-dispersion in capillary zone electrophoresis (CZE) at current densities as high as 1000 A/m 2$^{2}$ . We also show the efficacy of our moving mesh method over existing methods that cluster the grid points in the regions with large concentration gradients. We have integrated the adaptive Chebyshev pseudo-spectral method in the open-source SPYCE simulator and verified its implementation with other electrophoresis simulators.

5.
Platelets ; 33(6): 849-858, 2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-35109754

RESUMEN

Interrogating platelets and their densely packed, highly abundant receptor landscape is key to understand platelet clotting, a process that can save lives when stopping blood loss after an injury, but also kill when causing heart attack, stroke, or pulmonary embolism. The underlying key receptor distributions and interactions, in particular the relevance of integrin clustering, are not fully understood is because of highly abundant and densely distributed αIIbß3 receptors. This makes receptor distributions difficult to assess even by super-resolution fluorescence microscopy. Here, we combine dual-color expansion and confocal microscopy with colocalization analysis to assess platelet receptor organization without the need of a super-resolution microscope. We show that 4x expansion is highly straight-forward for super-resolution microscopy of platelets, while 10x expansion provides higher precision at the price of increased efforts in sample preparation and imaging. Quantifying various receptor colocalization scenarios we demonstrate that expansion microscopy can pinpoint receptor distributions and interactions in resting and activated platelets being superior to conventional methods that fail in such dense 3D scenarios with highly abundant receptors. We reveal the presence of αIIbß3 clusters in resting platelets, as well as in activated platelets, indicating that they contribute to the rapid platelet response during platelet clotting.


Asunto(s)
Plaquetas , Microscopía , Animales , Coagulación Sanguínea , Plaquetas/fisiología , Hemostasis , Humanos , Ratones , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria
6.
Ann Vasc Surg ; 81: 351-357, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34780940

RESUMEN

BACKGROUND: Data is scarce regarding the need for early re-amputation to a higher anatomic level. This study seeks to define outcomes and risk factors for re-amputation. METHODS: Patients undergoing primary major lower extremity amputation were identified within the 2012-2016 ACS-NSQIP database. Demographics, outcomes, and peri-operative characteristics were compared, and multivariable logistic regression model was used to determine association with early re-amputation. RESULTS: Over a 4-year period, 8306 below knee amputations and 6367 above knee amputations were identified. Thirty-day re-amputation occurred in 262 patients (1.8%) and was associated with increased length of stay (12.9 vs. 7.3 days, P < 0.001), higher rates of readmission (64.9% vs. 13.6%, P < 0.001), and overall complications (69.5% vs. 39.3%, P < 0.01). On multivariable analysis, advanced age (OR 1.02, CI 1.01-1.03), smoking (OR 1.75, CI 1.32-2.33), dialysis dependence (OR 1.67, CI 1.23-2.26), preoperative septic shock (OR 2.53, CI 1.29-4.97), and bleeding disorders (OR 1.72, CI 1.34-2.22) were associated with early re-amputation. CONCLUSIONS: Thirty-day re-amputation rates are low, but are associated with significant morbidity, prolonged hospitalization, and frequent readmissions.


Asunto(s)
Amputación Quirúrgica , Extremidad Inferior , Amputación Quirúrgica/efectos adversos , Humanos , Extremidad Inferior/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
7.
Bioinformatics ; 36(20): 4984-4990, 2020 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-32829394

RESUMEN

MOTIVATION: Facilitated by technological advances and expeditious decrease in the sequencing costs, whole-genome sequencing is increasingly implemented to uncover variations in cultivars/accessions of many crop plants. In tomato (Solanum lycopersicum), the availability of the genome sequence, followed by the resequencing of tomato cultivars and its wild relatives, has provided a prodigious resource for the improvement of traits. A high-quality genome resequencing of 84 tomato accessions and wild relatives generated a dataset that can be used as a resource to identify agronomically important alleles across the genome. Converting this dataset into a searchable database, including information about the influence of single-nucleotide polymorphisms (SNPs) on protein function, provides valuable information about the genetic variations. The database will assist in searching for functional variants of a gene for introgression into tomato cultivars. RESULTS: A recent release of better-quality tomato genome reference assembly SL3.0, and new annotation ITAG3.2 of SL3.0, dropped 3857 genes, added 4900 novel genes and updated 20 766 genes. Using the above version, we remapped the data from the tomato lines resequenced under the '100 tomato genome resequencing project' on new tomato genome assembly SL3.0 and made an online searchable Tomato Genomic Variations (TGVs) database. The TGV contains information about SNPs and insertion/deletion events and expands it by functional annotation of variants with new ITAG3.2 using SIFT4G software. This database with search function assists in inferring the influence of SNPs on the function of a target gene. This database can be used for selecting SNPs, which can be potentially deployed for improving tomato traits. AVAILABILITY AND IMPLEMENTATION: TGV is freely available at http://psd.uohyd.ac.in/tgv.


Asunto(s)
Solanum lycopersicum , ADN de Plantas , Genoma de Planta/genética , Genómica , Solanum lycopersicum/genética , Polimorfismo de Nucleótido Simple/genética
8.
Electrophoresis ; 42(7-8): 890-898, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33300129

RESUMEN

We present the formulation, implementation, and performance evaluation of the Fourier pseudo-spectral method for performing fast and accurate simulations of electrophoresis. We demonstrate the applicability of this method for simulating a wide variety of electrophoretic processes such as capillary zone electrophoresis, transient-isotachophoresis, field amplified sample stacking, and oscillating electrolytes. Through these simulations, we show that the Fourier pseudo-spectral method yields accurate and stable solutions on coarser computational grids compared with other nondissipative spatial discretization schemes. Moreover, due to the use of coarser grids, the Fourier pseudo-spectral method requires lower computational time to achieve the same degree of accuracy. We have demonstrated the application of the Fourier pseudo-spectral method for simulating realistic electrophoresis problems with current densities as high as 5000 A/m2 with over tenfold speed-up compared to the commonly used second-order central difference scheme, to achieve a given degree of accuracy. The Fourier pseudo-spectral method is also suitable for simulating electrophoretic processes involving a large number of concentration gradients, which render the adaptive grid-refinement techniques ineffective. We have integrated the numerical scheme in a new electrophoresis simulator named SPYCE, which we offer to the community as open-source code.


Asunto(s)
Isotacoforesis , Electrólitos , Electroforesis Capilar , Programas Informáticos
9.
Ann Vasc Surg ; 61: 254-260, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31394229

RESUMEN

BACKGROUND: The growth rate of abdominal aortic aneurysms (AAA) can vary depending on age, baseline diameter, blood pressure, race, and history of smoking. Paradoxically, previous studies show evidence of a protective effect of diabetes on the rate of AAA expansion despite its well-established role in the morbidity and mortality of cardiovascular disease. This study aims to investigate the impact diabetes plays on AAA growth within a Hispanic population. METHODS: Data were collected from patients who were predominantly Mexican-American at a single hospital site. Baseline and follow-up measures for AAA diameter were obtained from serial imaging studies. Demographics, medical history, the presence of type 2 diabetes, and medication use were extracted from hospital records. Linear mixed-effects growth models were used to calculate the overall AAA growth rate and to assess the difference in AAA growth rate between demographics, comorbidities, and medication use. RESULTS: The study comprised 201 patients (70.4% male) with a mean baseline age of 79.1 years, of whom 43.2% were diabetic. The average monthly AAA growth rate across all study participants was 0.15 mm (SE = 0.02 mm). Independently, the average AAA expansion rate for the diabetic and nondiabetic groups was 0.07 mm (SE = 0.04 mm) and 0.21 mm (SE = 0.03 mm) per month, respectively. This demonstrates a 65% lower linear AAA expansion rate per month in patients with diabetes. CONCLUSIONS: This study confirms a difference of AAA physiology between diabetics and nondiabetics in the Hispanic community. The observed significant difference in AAA growth rate may be a combination of factors associated with race/ethnicity, prevalence of diabetes mellitus, and low compliance with diabetic control exhibited in the Mexican-American population.


Asunto(s)
Aneurisma de la Aorta Abdominal/etnología , Diabetes Mellitus/etnología , Americanos Mexicanos , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico , Diabetes Mellitus/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Texas/epidemiología , Factores de Tiempo
10.
Plant J ; 92(3): 495-508, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28779536

RESUMEN

The identification of mutations in targeted genes has been significantly simplified by the advent of TILLING (Targeting Induced Local Lesions In Genomes), speeding up the functional genomic analysis of animals and plants. Next-generation sequencing (NGS) is gradually replacing classical TILLING for mutation detection, as it allows the analysis of a large number of amplicons in short durations. The NGS approach was used to identify mutations in a population of Solanum lycopersicum (tomato) that was doubly mutagenized by ethylmethane sulphonate (EMS). Twenty-five genes belonging to carotenoids and folate metabolism were PCR-amplified and screened to identify potentially beneficial alleles. To augment efficiency, the 600-bp amplicons were directly sequenced in a non-overlapping manner in Illumina MiSeq, obviating the need for a fragmentation step before library preparation. A comparison of the different pooling depths revealed that heterozygous mutations could be identified up to 128-fold pooling. An evaluation of six different software programs (camba, crisp, gatk unified genotyper, lofreq, snver and vipr) revealed that no software program was robust enough to predict mutations with high fidelity. Among these, crisp and camba predicted mutations with lower false discovery rates. The false positives were largely eliminated by considering only mutations commonly predicted by two different software programs. The screening of 23.47 Mb of tomato genome yielded 75 predicted mutations, 64 of which were confirmed by Sanger sequencing with an average mutation density of 1/367 Kb. Our results indicate that NGS combined with multiple variant detection tools can reduce false positives and significantly speed up the mutation discovery rate.


Asunto(s)
Metanosulfonato de Etilo/efectos adversos , Genómica/métodos , Mutágenos/efectos adversos , Mutación/efectos de los fármacos , Programas Informáticos , Solanum lycopersicum/genética , Alelos , Biblioteca de Genes , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento , Genética Inversa , Análisis de Secuencia de ADN
11.
J Orthod ; 45(1): 4-10, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29281939

RESUMEN

OBJECTIVE: The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages. DESIGN: Cross-sectional study. SETTING: Maulana Azad Institute of Dental Sciences, New Delhi, India. PARTICIPANTS: 150 subjects (75 males and 75 females) in the age group of 8-20 years. METHODS: Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann-Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages. RESULTS: Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p < .01). CONCLUSIONS: BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.


Asunto(s)
Fosfatasa Alcalina , Factor I del Crecimiento Similar a la Insulina , Biomarcadores , Vértebras Cervicales , Estudios Transversales , Femenino , Humanos , Masculino
12.
J Contemp Dent Pract ; 19(12): 1538-1545, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30713186

RESUMEN

AIM: To investigate the biofilm formation on Prosthetic materials as affected by type II diabetes mellitus, Candida albicans and Streptococcus mutans. MATERIALS AND METHODS: Two types of saliva, natural saliva, and artificial saliva were collected and prepared respectively. The natural saliva was divided into diabetic and non-diabetic saliva. The artificial saliva was further divided into two groups, one inoculated with Streptococcus mutans and the second with Candida albicans. The 150 samples of various prosthetic materials were prepared using nickel-chromium alloy, ceramic, soft liner, tooth molding powder; heat cured the acrylic resin. The samples were then immersed in natural saliva and artificial saliva and studied for biofilm formation. RESULTS: Diabetic saliva formed more biofilm than non-diabetic saliva. Streptococcus mutans were able to form more biofilm than Candida albicans in artificial saliva on constitutive androstane receptor (hCAR) and spinal length (SL). In Diabetic saliva, there was a significant difference in the biofilm formation seen between MC and NCA (p < 0.05). No biofilm was formed on hCAR in natural saliva (diabetic or non-diabetic). In artificial saliva inoculated with Candida albicans and streptococcus mutans there is a significant difference in the biofilm formation in all the materials except NCA. CONCLUSION: Diabetic saliva has more potential to form biofilm than non-diabetic saliva. Also, Candida albicans and Streptococcus mutans both can form a biofilm on materials used with the maximum formation on hCAR. Smoother materials formed less biofilm than rougher surfaces like hCAR, PCM, SL. CLINICAL SIGNIFICANCE: It is desirable for dental restorative materials to have a low susceptibility for accumulation and formation of biofilm as it may lead to pathologies such as dental caries, periodontal disease, peri-implantitis, etc. which are plaque-related. The most commonly used materials in prosthodontics have been used in the study to establish a direct relationship with the formation of biofilm, this, in turn, helps us to take the right call in choosing a material for a patient with an already compromised systemic condition.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Candida albicans/fisiología , Materiales Dentales , Prótesis Dental/microbiología , Diabetes Mellitus Tipo 2/microbiología , Saliva Artificial , Saliva/microbiología , Streptococcus mutans/fisiología , Resinas Acrílicas , Cerámica , Aleaciones de Cromo , Revestimiento para Colado Dental , Porcelana Dental , Resinas Sintéticas , Propiedades de Superficie
13.
J Vasc Surg ; 66(6): 1653-1658.e1, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28711400

RESUMEN

OBJECTIVE: Although few studies have reported outcomes after branched or fenestrated endovascular aortic aneurysm repair (FEVAR) of abdominal aortic aneurysms involving visceral vessels (AAA-Vs), no multi-institutional study has compared FEVAR with open surgery (OS) for AAA-Vs. Our objective was to compare 30-day outcomes after FEVAR vs OS for AAA-Vs. METHODS: Patients who underwent FEVAR (n = 535) and OS (n = 1207) for elective AAA-Vs were identified from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) 2008 to 2013 database. Thoracoabdominal aneurysms were excluded. Univariable and multivariable logistic regression analyses were performed. RESULTS: There were more men (82% vs 72%; P < .0001), diabetic patients (16% vs 11%; P = .005), patients with dependent functional status (4% vs 2%; P = .002), and nonsmokers (70% vs 56%; P < .0001) in the FEVAR group vs OS. There was no difference in rates of chronic obstructive pulmonary disease, cardiac history, peripheral artery disease, hypertension, and dialysis (P > .05). FEVAR had fewer major postoperative pulmonary complications (3.0% vs 19.0%; P < .0001), less renal failure requiring dialysis (1.9% vs 6.4%; P < .0001), less frequent cardiac arrest or myocardial infarction (2.2% vs 5.8%; P = .001), less bleeding with major transfusion (17.4% vs 50.2%; P < .0001), and decreased incidence of return to the operating room (4.5% vs 9.6%; P < .0001) and death (2.4% vs 4.7%; P = .02). The median length of stay was also significantly shorter for FEVAR (2 days vs 7 days; P < .0001). On multivariable analyses, OS was associated with higher risk than FEVAR for 30-day death (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.3-5.0), pulmonary complications (OR, 8.8; 95% CI, 5.1-15.0), cardiac complications (OR, 3.4; 95% CI, 1.8-6.6), renal failure needing dialysis (OR, 3.8; 95% CI, 1.9-7.7), and return to the operating room (OR 2.5; 95% CI, 1.6-4.0). CONCLUSIONS: FEVAR is associated with a lower risk for 30-day mortality and adverse events compared with OS for AAA-Vs.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Distribución de Chi-Cuadrado , Comorbilidad , Bases de Datos Factuales , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Tiempo de Internación , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Diseño de Prótesis , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
14.
J Vasc Surg ; 62(1): 22-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25935276

RESUMEN

OBJECTIVE: Although placement of an open iliac conduit for endovascular aortic aneurysm repair (EVAR) is generally felt to result in higher morbidity and mortality, published literature is scarce. Our objective was to assess 30-day outcomes after elective EVAR with an open iliac conduit using a multi-institutional database. METHODS: Patients who underwent elective EVAR (n = 14,339) for abdominal aortic aneurysm were identified from the American College of Surgeons National Surgical Quality Improvement Program 2005 to 2011 database. Univariable and multivariable logistic regression analyses were performed. RESULTS: An open iliac conduit was used in 231 patients (1.6%), and the remainder had femoral exposure or percutaneous EVAR. Women comprised 32% of patients with iliac conduits in contrast to 17% of those without iliac conduits. Patients with iliac conduits were older and had a lower body mass index. Univariable analysis showed patients with open iliac conduits had a higher incidence of postoperative pneumonia (3.0% vs 1.1%), ventilator dependence (4.8% vs 1.0%), renal failure (3.0% vs 0.7%), cardiac arrest or myocardial infarction (5.2% vs 1.1%), return to the operating room (9.1% vs 3.7%), major morbidity (16.0 vs 6.6%), and death (3.0% vs 0.9%). On multivariable analysis, the use of open iliac conduits was associated with higher risk of 30-day mortality (odds ratio, 2.7; 95% confidence interval, 1.2-6.0) and 30-day major morbidity (odds ratio, 2.3; 95% confidence interval, 1.6-3.3). CONCLUSIONS: Patients with open iliac conduits for EVAR are more likely to be female and have higher postoperative morbidity and mortality. For patients with complex iliac artery disease, conduits are a viable alternative after EVAR to be performed, albeit at an increased risk. These data do suggest the need for lower-profile grafts and other alternative strategies for navigating complex iliac artery disease.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular , Prótesis Vascular , Procedimientos Endovasculares , Arteria Ilíaca/cirugía , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/mortalidad , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/mortalidad , Distribución de Chi-Cuadrado , Bases de Datos Factuales , Procedimientos Quirúrgicos Electivos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Selección de Paciente , Diseño de Prótesis , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
15.
J Vasc Surg ; 61(3): 683-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25499711

RESUMEN

OBJECTIVE: Rapid and objective preoperative assessment of patients undergoing carotid endarterectomy (CEA) remains problematic. Preoperative variables correlate with increased morbidity and mortality, yet no easily implemented tool exists to stratify patients. We determined the relationship between our fully implemented frailty-based bedside Risk Analysis Index (RAI) and complications after CEA. METHODS: Patients undergoing CEA in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2011 were included. Variables of frailty RAI were matched to preoperative NSQIP variables, and outcomes including stroke, mortality, myocardial infarction (MI), and length of stay were analyzed. We further analyzed patients who were symptomatic and asymptomatic before CEA. RESULTS: With use of the NSQIP database, 44,832 patients undergoing CEA were analyzed (17,696 [39.5%] symptomatic; 27,136 [60.5%] asymptomatic). Increasing frailty RAI score correlated with increasing stroke, death, and MI (P < .0001) as well as with length of stay. RAI demonstrated increasing risk of stroke and death on the basis of risk stratification (low risk [0-10], 2.1%; high risk [>10], 5.0%). Among patients undergoing CEA, 88% scored low (<10) on the RAI. In symptomatic patients, the risk of stroke and death for patients with a score of ≤10 is 2.9%, whereas if the RAI score is 11 to 15, it is 5.0%; 16 to 20, 6.9%; and >21, 8.6%. In asymptomatic patients, the risk of stroke and death for patients with a score of ≤10 is 1.6%, whereas if the RAI score is 11 to 15, it is 2.9%; 16 to 20, 5.2%; and >21, 6.2%. CONCLUSIONS: Frailty is a predictor of increased stroke, mortality, MI, and length of stay after CEA. An easily implemented RAI holds the potential to identify a limited subset of patients who are at higher risk for postoperative complications and may not benefit from CEA.


Asunto(s)
Enfermedades de las Arterias Carótidas/cirugía , Técnicas de Apoyo para la Decisión , Endarterectomía Carotidea/efectos adversos , Indicadores de Salud , Estado de Salud , Anciano , Anciano de 80 o más Años , Enfermedades Asintomáticas , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/mortalidad , Bases de Datos Factuales , Endarterectomía Carotidea/mortalidad , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Selección de Paciente , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
18.
J Biol Chem ; 288(37): 26583-93, 2013 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-23880771

RESUMEN

Human bispecific antibodies have great potential for the treatment of human diseases. Although human IgG1 bispecific antibodies have been generated, few attempts have been reported in the scientific literature that extend bispecific antibodies to other human antibody isotypes. In this paper, we report our work expanding the knobs-into-holes bispecific antibody technology to the human IgG4 isotype. We apply this approach to generate a bispecific antibody that targets IL-4 and IL-13, two cytokines that play roles in type 2 inflammation. We show that IgG4 bispecific antibodies can be generated in large quantities with equivalent efficiency and quality and have comparable pharmacokinetic properties and lung partitioning, compared with the IgG1 isotype. This work broadens the range of published therapeutic bispecific antibodies with natural surface architecture and provides additional options for the generation of bispecific antibodies with differing effector functions through the use of different antibody isotypes.


Asunto(s)
Anticuerpos Biespecíficos/inmunología , Regulación de la Expresión Génica , Inmunoglobulina G/inmunología , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Animales , Anticuerpos Biespecíficos/biosíntesis , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Inmunoglobulina G/biosíntesis , Pulmón/inmunología , Pulmón/metabolismo , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos BALB C , Plásmidos/metabolismo , Ingeniería de Proteínas/métodos , Resonancia por Plasmón de Superficie
19.
J Vasc Surg ; 59(2): 473-82, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24239519

RESUMEN

OBJECTIVE: Existing literature on readmission after vascular surgery is limited. The upcoming reduction in Medicare reimbursement for institutions with high readmission rates mandates an accurate understanding of this issue. In this study, we characterize the frequency and causes of 30-day unplanned readmissions after elective vascular surgery. METHODS: Patients who underwent elective carotid endarterectomy (CEA), endovascular aortic repair (EVAR), open abdominal aortic aneurysm (oAAA) repair, or infrainguinal bypass grafting (BPG) were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2011 database (n = 11,246). Multivariable logistic regression was used to determine variables that contributed to 30-day unplanned readmissions for each surgery type. RESULTS: The unadjusted unplanned readmission rates after the four vascular procedures ranged from 6.5% for CEA to 15.7% for BPG. In multivariable analyses, patient comorbidities were associated with unplanned readmission after BPG and CEA (P < .05), whereas postoperative complications were more consistently associated with unplanned readmission after EVAR and oAAA repair (P < .05). For all procedures, complications leading to readmission developed more frequently after discharge. Thirty-day mortality was significantly higher in readmitted patients after BPG (1.9% vs 0.3%), EVAR (3.9% vs 0.1%), and CEA (2.2% vs 0.2%; P < .001 for each), but not after oAAA repair. CONCLUSIONS: Select comorbidities and postoperative complications contribute to unplanned readmissions after vascular surgery. The characteristics of readmitted patients vary with the type of procedure. Interventions designed to mitigate these factors have the potential to reduce unplanned readmissions but likely need to vary with the type of vascular treatment.


Asunto(s)
Readmisión del Paciente , Complicaciones Posoperatorias/terapia , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/cirugía , Distribución de Chi-Cuadrado , Comorbilidad , Procedimientos Quirúrgicos Electivos , Endarterectomía Carotidea/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Factores de Tiempo , Estados Unidos , Injerto Vascular/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad
20.
J Vasc Surg ; 60(6): 1439-45, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25103257

RESUMEN

OBJECTIVE: Two randomized trials to date have compared open surgery (OS) and endovascular (EVAR) repair for ruptured abdominal aortic aneurysm (rAAA); however, neither addressed optimal management of unstable patients. Single-center reports have produced conflicting data regarding the superiority of one vs the other, with the lack of statistical power due to low patient numbers. Furthermore, previous studies have not delineated between the outcomes of stable patients with a contained rupture vs those patients with instability. Our objective was to compare 30-day outcomes in patients undergoing OS vs EVAR for all rAAAs, focusing specifically on patients with instability. METHODS: Patients who underwent repair of rAAA were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database (2005 to 2010). Unstable patients with rupture were identified as those who were American Society of Anesthesiologists Physical Status Classification 4 or 5 requiring emergency repair with at least one of the following: preoperative shock, preoperative transfusion of >4 units, preoperative intubation, or preoperative coma or impaired sensorium. Univariable and multivariable logistic regression analyses were performed. RESULTS: Of the 1447 patients with rAAA, 65.5% underwent OS and 34.5% EVAR. Forty-five percent were unstable, and for these patients, OS was performed in 71.3% and EVAR in 28.7%. The 30-day mortality rate was 47.9% (OS, 52.8%; EVAR, 35.6%; P < .0001) for unstable rAAAs and was 22.4% for stable rAAAs (OS, 26.3%; EVAR, 16.4%; P = .001). Amongst patients with unstable rAAA, 26% had a myocardial infarction or cardiac arrest ≤ 30 days (OS, 29.0%; EVAR, 19.1%; P = .006), and 17% needed postoperative dialysis (OS, 18.7%; EVAR, 12.8%; P = .04). Amongst patients with stable rAAA, 13.6% had a myocardial infarction or cardiac arrest ≤ 30 days (OS, 14.9%; EVAR, 11.6%; P = .20), and 11.5% needed postoperative dialysis (OS, 13.3%; EVAR, 8.7%; P = .047). Multivariable analyses showed OS was a predictor of 30-day mortality for unstable rAAA (odds ratio, 1.74; 95% confidence interval, 1.16-2.62) and stable rAAA (odds ratio, 1.64; 95% confidence interval, 1.10-2.43). CONCLUSIONS: Approximately one-third of patients treated for rAAA undergo EVAR in NSQIP participating hospitals. Not surprisingly, unstable patients have less favorable outcomes. In both stable and unstable rAAA patients, EVAR is associated with a diminished 30-day mortality and morbidity.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/cirugía , Procedimientos Endovasculares , Hemodinámica , Procedimientos Quirúrgicos Vasculares , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/mortalidad , Aneurisma de la Aorta Abdominal/fisiopatología , Rotura de la Aorta/diagnóstico , Rotura de la Aorta/mortalidad , Rotura de la Aorta/fisiopatología , Distribución de Chi-Cuadrado , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/terapia , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad
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