Background Antibody mediated rejection (AMR) is an important cause of graft loss in the post heart transplant period. The following study was conducted to determine differences between survivors and ...nonsurvivors who developed post heart transplant AMR. Methods We retrospectively reviewed the charts of patients who received a heart transplant between January 1993 and December 2002. Patients with biopsy proven AMR were identified. This group was divided into survivors and nonsurvivors. Groups were compared with regards to demographics, T-cell flow panel of reactive antibodies (PRA), flow cross-matches (anti-donor HLA Class I and II), and short- and long-term outcomes. Results of endomyocardial biopsies were collected to allow calculation of sensitivity, specificity, negative- and positive predictive values as well as accuracy of immunoglobulins and complement split products in association to death. Results A total of 65 patients (8.9%) were diagnosed with AMR. Mean age was 48 y (range: 8–68 y) and 53.8% were males. Episodes of hemodynamic instability associated with AMR were observed in 37% of patients. Only two deaths were directly attributed to acute AMR. Nearly 20% of AMR patients developed transplant coronary artery disease. Univariate analysis identified T-PRA ( P < 0.001), mean T-cell molecules of equivalent soluble fluorochrome (MESF) ( P < 0.001) and mean B-cell MESF ( P < 0.001) as possible factors associated with death. Neither demographics of complement split products were associated to late death. Conclusion When studying patients with AMR, pretransplant T-PRA, T-cell, and B-cell MESF may identify individuals at risk of late death.
Despliega la estructura de negocio para la creación de una empresa de consolidación de ventas a través de un Marketplace On-Line, que ofrece un canal alternativo de comercialización para las pequeñas ...y medianas empresas locales, ubicadas en los grandes emporios comerciales, brindando de igual manera la posibilidad de venta de una gran cantidad de productos, para atender los requerimientos y satisfacer las necesidades de los consumidores finales. Como ventajas competitivas se consideran aspectos que llegan a ser importantes para el comercializador, como es el de tener acceso a una plataforma de venta ya que por el tamaño de las empresas y el nivel de inversión, no cuentan con la capacidad de acceder a este tipo de canal de venta, en donde se les ofrece poder contar con una herramienta intuitiva para ofrecer sus productos y que estos sean visualizados por un gran número de personas, aumentando así las posibilidades de compra exitosa. De la misma forma, hacia el consumidor final se ofrecen alternativas para su compra como lo es la plataforma intuitiva que hará de su compra más fácil y eficiente, ofreciéndole una mayor comodidad, ahorro de tiempo y dinero, contando con su producto en el menor tiempo posible. Al igual se ofrecen otras herramientas, diferenciadoras, para las adquisiciones de los productos, para realizar una compra segura, como lo son los Showrooms, las ventas por videoconferencia y, entre otras, la adquisición de los productos en las tiendas más cercanas a través de la geolocalización. Las cifras vistas en este documento sustentan que las ventas por internet aumentarán en los siguientes años y las empresas tendrán aún más posibilidad de ofrecer sus productos a través de este canal de ventas, captando una mayor cantidad de clientes y logrando la fidelización del consumidor final. En el análisis de mercado se evidencia la relación de crecimiento que tiene el comercio electrónico en donde para el año 2016 se espera que tenga un crecimiento del 30% con respecto al año anterior, donde se encuentran categorías líderes en el mercado que han sido consideradas en esta propuesta. La estrategia de marketing tiene como objetivo lograr una penetración del mercado de comerciantes representados en las pequeñas y medianas empresas, integrando al consumidor final a través de una plataforma web que llegue a ser reconocida y la mejor en su categoría. Este plan de negocio por tanto muestra un proyecto que requiere de un capital que se puede obtener en el medio y en función a las variables de mercado presentadas, al modelo de negocio planteado y a las diferentes estrategias de marketing y operación poder llevarlo a buen puerto con una caja final por encima de los 10 millones de nuevos soles, además de no tener que necesitar préstamos y en el caso de necesitarlos poder afrontarlos sin ningún problema como muestran los ratios financieros; por ello es un proyecto viable y de interés socio económico para el Perú pues busca reactivar económicamente a sus emporios económicos además que ayudará a la formalización de los comerciantes.
Tesis
To compare perfused capillary density (PCD) in diabetic patients and healthy controls using optical coherence tomography angiography (OCTA).
Forty controls, 36 diabetic subjects without clinical ...retinopathy (NoDR), 38 with nonproliferative retinopathy (NPDR), and 38 with proliferative retinopathy (PDR) were imaged using spectral-domain optical coherence tomography. A 3 × 3-mm full-thickness parafoveal OCTA scan was obtained from each participant. Following manual delineation of the foveal avascular zone (FAZ), FAZ area, perimeter, and acircularity index were determined. Seven consecutive equidistant 200-μm-wide annular segments were drawn at increasing eccentricities from the FAZ margin. Annular PCD (%) was defined as perfused capillary area divided by the corresponding annulus area after subtraction of noncapillary blood vessel areas. Nonparametric Kruskal-Wallis testing with Bonferroni correction was performed in pairwise comparisons of group PCD values.
The NoDR group demonstrated consistently higher PCD compared to the control group in all 7 annuli, reaching statistical significance (36.6% ± 3.30% vs 33.6% ± 3.98%, P = .034) at the innermost annulus (FAZ margin to 200 μm out). The NPDR and PDR groups demonstrated progressively decreasing PCD. Differences in FAZ metrics between the NoDR and control groups did not reach statistical significance.
Relative to healthy controls, increased PCD values in the NoDR group likely represent an autoregulatory response to increased metabolic demand, while the decrease in PCD that follows in NPDR and PDR results largely from an incremental loss of capillary segments. These findings, consistent with previous studies, demonstrate the potential of OCTA as a clinical tool for earlier objective detection of preclinical diabetic retinopathy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
To examine interocular asymmetry of foveal avascular zone (FAZ) and parafoveal capillary density metrics in sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A).
This ...cross-sectional, retrospective study evaluated SCR patients and unaffected controls who underwent 3x3mm macular OCT-A imaging using a spectral domain-OCT system. FAZ (area, perimeter, and acircularity index) and parafoveal capillary density metrics were computed for both eyes of each participant. In unaffected controls, interocular difference in FAZ and parafoveal capillary density metrics were evaluated using Bland-Altman plots. SCR patients with interocular difference outside the upper 97.5% and lower 2.5% limits of agreement from controls were defined as having interocular asymmetry. Area under receiver operating characteristic curve (AROC) was also performed to determine the ability of the absolute interocular difference to differentiate between subjects with SCR-including non-proliferative SCR (NP-SCR) and proliferative SCR (P-SCR)-and unaffected controls.
Thirty-one patients with SCR (21 NP-SCR and 10 P-SCR) and 14 race-matched and age-matched controls were included for analysis. Interocular asymmetry was seen for all FAZ and parafoveal capillary density metrics in NP-SCR and P-SCR subjects. SCR subjects showed greater disease severity in the left-eye for FAZ and parafoveal capillary density metrics.
NP-SCR and P-SCR patients demonstrated quantifiable interocular asymmetry in FAZ and parafoveal capillary density metrics compared to unaffected subjects, with left-eye predominance in disease severity.
Hemodynamic changes surrounding the optic nerve head are known to occur in thyroid-related orbitopathy (TRO). This pilot study explores the capillary and non-capillary peripapillary perfusion changes ...of the retina in TRO eyes without dysthyroid optic neuropathy (DON) using optical coherence tomography angiography (OCT-A).
Non-capillary and capillary peripapillary perfusion densities were calculated using single 4.5 × 4.5mm en face "RPC layer" OCT-A scans of 8 TRO patients without DON (8 eyes, mean age 40.6 years, range 23-69 years). Results were compared to a previously published dataset of 133 healthy controls (133 eyes, mean 41.5 years, range 11-83 years). The strength of association was measured between OCT-A perfusion densities and clinical measures of TRO.
Non-capillary peripapillary perfusion density in TRO eyes was found to be significantly decreased compared to healthy controls (TRO group 15.4 ± 2.9% vs controls 21.5 ± 3.1%; p < 0.0001). Capillary peripapillary perfusion densities showed no significant difference (TRO group 42.5 ± 1.8% vs controls 42.5 ± 1.5%; p = 1.0). Clinical measures of disease did not correlate well with OCT-A perfusion densities (p>0.05).
These findings may represent decreased blood flow and subclinical ischemia to the optic nerve. We discuss possible pathogenic mechanisms of thyroid-related vasculopathy, including vessel wall thickening due to immunologically-induced media enlargement.
Solar retinopathy is a rare form of retinal injury that occurs after direct sungazing.
To enhance understanding of the structural changes that occur in solar retinopathy by obtaining high-resolution ...in vivo en face images.
Case report of a young adult woman who presented to the New York Eye and Ear Infirmary with symptoms of acute solar retinopathy after viewing the solar eclipse on August 21, 2017.
Results of comprehensive ophthalmic examination and images obtained by fundus photography, microperimetry, spectral-domain optical coherence tomography (OCT), adaptive optics scanning light ophthalmoscopy, OCT angiography, and en face OCT.
The patient was examined after viewing the solar eclipse. Visual acuity was 20/20 OD and 20/25 OS. The patient was left-eye dominant. Spectral-domain OCT images were consistent with mild and severe acute solar retinopathy in the right and left eye, respectively. Microperimetry was normal in the right eye but showed paracentral decreased retinal sensitivity in the left eye with a central absolute scotoma. Adaptive optics images of the right eye showed a small region of nonwaveguiding photoreceptors, while images of the left eye showed a large area of abnormal and nonwaveguiding photoreceptors. Optical coherence tomography angiography images were normal in both eyes. En face OCT images of the right eye showed a small circular hyperreflective area, with central hyporeflectivity in the outer retina of the right eye. The left eye showed a hyperreflective lesion that intensified in area from inner to middle retina and became mostly hyporeflective in the outer retina. The shape of the lesion on adaptive optics and en face OCT images of the left eye corresponded to the shape of the scotoma drawn by the patient on Amsler grid.
Acute solar retinopathy can present with foveal cone photoreceptor mosaic disturbances on adaptive optics scanning light ophthalmoscopy imaging. Corresponding reflectivity changes can be seen on en face OCT, especially in the middle and outer retina. Young adults may be especially vulnerable and need to be better informed of the risks of viewing the sun with inadequate protective eyewear.
Enlargement of the foveal avascular zone (FAZ) due to progressive capillary nonperfusion is associated with visual deterioration in patients with diabetic retinopathy. The FAZ area has long been ...considered an important clinical marker of advancing retinopathy. However, a large body of literature shows that the FAZ area varies considerably in healthy eyes, resulting in substantial overlap between controls and diabetics, thus reducing its discriminatory value. In this study, within-subject FAZ area enlargement was obtained by the comparison of the structural FAZ area to the functional FAZ area using simultaneously-acquired, corresponding
OCT reflectance and OCT angiography images. Our study suggests that
OCT reflectance images provide useful anatomic baselines of structural FAZ morphology prior to the onset of disease. Measurements of within-subject FAZ area enlargement appear to be a more sensitive method for identifying the onset of diabetic retinopathy as compared to using OCT angiographic measurements of FAZ alone.
Anti-HER2 targeted therapies have recently demonstrated clinical activity in the treatment of high-grade endometrial carcinomas (ECs), particularly serous carcinomas with HER2 amplification and/or ...overexpression. Intratumor heterogeneity of HER2 amplification or HER2 genetic intratumor heterogeneity (G-ITH) has been associated with resistance to anti-HER2 therapies in breast and gastroesophageal cancers; however, its clinical relevance in EC is unknown. To characterize HER2 G-ITH in EC, archival specimens from a clinically annotated cohort of 57 ECs treated with trastuzumab or trasutuzmab emtansine in the recurrent (n = 38) or adjuvant (n = 19) setting were subjected to central pathology review, HER2 assessment by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and next-generation sequencing. HER2 G-ITH, defined as HER2 amplification in 5% to 50% of tumor cells examined by FISH, was identified in 36% (19/53) of ECs and was associated with lower HER2 copy number and levels of protein expression. HER2 IHC revealed spatially distinct areas of strong expression juxtaposed with areas of low/absent expression in tumors with the "cluster" pattern of G-ITH, whereas the "mosaic" pattern was typically associated with a diffuse admixture of cells with variable levels of HER2 expression. HER2 G-ITH was frequently observed in cases with IHC/FISH or FISH/next-generation sequencing discrepancies and/or with an equivocal/negative FISH result (9/13, 69%). Although the objective response rate to anti-HER2 therapy in recurrent ECs was 52% (13/25) for tumors lacking HER2 G-ITH, none (0%, 0/10) of the patients with HER2 G-ITH achieved a complete or partial response (P = .005). HER2 G-ITH was significantly associated with worse progression-free survival (hazard ratio, 2.88; 95% CI, 1.33-6.27; P = .005) but not overall survival. HER2 IHC score, HER2/CEP17 ratio, HER2 copy number, histologic subtype, and other genetic alterations, including PIK3CA hotspot mutations, were not significantly associated with therapeutic response or survival outcomes. Treatment responses were not restricted to serous carcinomas, supporting consideration of anti-HER2 therapy in patients with HER2-positive high-grade ECs of non-serous histology. Our results demonstrate that HER2 G-ITH is an important determinant of response to trastuzumab and trastuzumab emtansine in EC, providing a rationale for the development of novel therapeutic strategies to target HER2-nonamplified resistant tumor subpopulations, such as HER2 antibody-drug conjugates with bystander effects.
Genetic testing for Li-Fraumeni syndrome (LFS) is performed by using blood specimens from patients selected based on phenotype-dependent guidelines. This approach is problematic for understanding the ...LFS clinical spectrum because patients with nonclassical presentations are missed, clonal hematopoiesis-related somatic blood alterations cannot be distinguished from germline variants, and unrelated tumors cannot be differentiated from those driven by germline TP53 defects.
To provide insights into the LFS-related cancer spectrum, we analyzed paired tumor-blood DNA sequencing results in 17 922 patients with cancer and distinguished clonal hematopoiesis-related, mosaic, and germline TP53 variants. Loss of heterozygosity and TP53 mutational status were assessed in tumors, followed by immunohistochemistry for p53 expression on a subset to identify those lacking biallelic TP53 inactivation.
Pathogenic/likely pathogenic TP53 variants were identified in 50 patients, 12 (24.0%) of which were clonal hematopoiesis related and 4 (8.0%) of which were mosaic. Twelve (35.3%) of 34 patients with germline TP53 variants did not meet LFS testing criteria. Loss of heterozygosity of germline TP53 variant was observed in 96.0% (95% confidence interval CI = 79.7% to 99.9%) of core LFS spectrum-type tumors vs 45.5% (95% CI = 16.8% to 76.6%) of other tumors and 91.3% (95% CI = 72.0% to 98.9%) of tumors from patients who met LFS testing criteria vs 61.5% (95% CI = 31.6% to 86.1%) of tumors from patients who did not. Tumors retaining the wild-type TP53 allele exhibited wild-type p53 expression.
Our results indicate that some TP53 variants identified in blood-only sequencing are not germline and a substantial proportion of patients with LFS are missed based on current testing guidelines. Additionally, a subset of tumors from patients with LFS do not have biallelic TP53 inactivation and may represent cancers unrelated to their germline TP53 defect.
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