Patients Undergoing Ileoanal Pouch Surgery Experience a Constellation of Symptoms and Consequences Representing a Unique Syndrome: A Report from the Patient-Reported Outcomes After Pouch Surgery (PROPS) Delphi Consensus Study

Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research.The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function.This was a Delphi consensus study.Three rounds of surveys were used to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement.Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients, including patients, colorectal surgeons, and gastroenterologists or other clinicians.A consensus statement was the main outcome.patients, 62 colorectal surgeons, and 48 gastroenterologists or nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement.The study was limited by online recruitment bias.This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function. See Video Abstract at http://links.lww.com/DCR/B571.Un Informe de los Resultados Reportados por los Pacientes Posterior a la Cirugía de Reservorio (PROPS) Estudio de Consenso DelphiANTECEDENTES:Los resultados funcionales después de la creación del reservorio ileoanal han sido estudiados; sin embargo, existe una gran variabilidad en la forma en que se definen y reportan los resultados relevantes. Más importante aún, la perspectiva de los pacientes no se ha representado a la hora de decidir qué resultados deberían ser el foco de investigación.OBJETIVO:El objetivo principal era crear en el paciente una definición centrada de los síntomas principales que debería incluirse en los estudios futuros de la función del reservorio.DISEÑO:Estudio de consenso Delphi.ENTORNO CLINICO:Se emplearon tres rondas de encuestas para seleccionar elementos de alta prioridad. La votación de la encuesta fue seguida por una serie de reuniones de consulta de pacientes en línea que se utilizan para aclarar las tendencias de votación. Se realizo una reunión de consenso final en línea con representación de los tres paneles de expertos para finalizar una declaración de consenso.PACIENTES:Se eligieron partes interesadas expertas para correlacionar con el escenario clínico del equipo multidisciplinario que atiende a los pacientes con reservorio: pacientes, cirujanos colorrectales, gastroenterólogos / otros médicos.PRINCIPALES MEDIDAS DE VALORACION:Declaración de consenso.RESULTADOS:Ciento noventa y cinco pacientes, 62 cirujanos colorrectales y 48 gastroenterólogos / enfermeras especialistas completaron las tres rondas Delphi. 53 pacientes participaron en grupos focales en línea. 161 interesados participaron en la reunión de consenso final. Al concluir la reunión de consenso, siete síntomas intestinales y siete consecuencias de someterse a una cirugía de reservorio ileoanal se incluyeron en la declaración de consenso final.LIMITACIONES:Sesgo de reclutamiento en línea.CONCLUSIONES:Este estudio es el primero en identificar resultados funcionales claves después de la cirugía de reservorio con información directa de un gran panel de pacientes con reservorio ileoanal. La inclusión de pacientes en todas las etapas del proceso de consenso permitió un verdadero enfoque centrado en el paciente para definir los dominios principales en los que debería centrarse los estudios futuros de la función del reservorio. Consulte Video Resumen en http://links.lww.com/DCR/B571

Patients Undergoing Ileoanal Pouch Surgery Experience a Constellation of Symptoms and Consequences Representing a Unique Syndrome: A Report From the Patient-Reported Outcomes After Pouch Surgery (PROPS) Delphi Consensus Study

The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function.Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research.Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients: patients, colorectal surgeons, gastroenterologists/other clinicians. Three rounds of surveys were employed to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement.One hundred ninety-five patients, 62 colorectal surgeons, and 48 gastroenterologists/nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement.This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function

In situ production of titanium dioxide nanoparticles in molten salt phase for thermal energy storage and heat-transfer fluid applications

In this study, TiO2 nanoparticles (average particle size 16 nm) were successfully produced in molten salt phase and were showed to significantly enhance the specific heat capacity of a binary eutectic mixture of sodium and potassium nitrate (60/40) by 5.4 % at 390 °C and 7.5 % at 445 °C for 3.0 wt% of precursors used. The objective of this research was to develop a cost-effective alternate method of production which is potentially scalable, as current techniques utilized are not economically viable for large quantities. Enhancing the specific heat capacity of molten salt would promote more competitive pricing for electricity production by concentrating solar power plant. Here, a simple precursor (TiOSO4) was added to a binary eutectic mixture of potassium and sodium nitrate, heated to 450 °C, and cooled to witness the production of nanoparticles

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.scientific project (POCI/BIA-BCM/59252/2004) financed by the Portuguese Science and Technology Foundation (FCT). FCT also provided research grants as follows: Programa Ciência 2007 (FCT) for Joana Paredes, and PhD research grants for Ana Sofia Ribeiro (SFRH/BD/36096/2007) and André Albergaria (SFRH/BD/15316/2005)

Rickettsiae Induce Microvascular Hyperpermeability via Phosphorylation of VE-Cadherins: Evidence from Atomic Force Microscopy and Biochemical Studies

The most prominent pathophysiological effect of spotted fever group (SFG) rickettsial infection of microvascular endothelial cells (ECs) is an enhanced vascular permeability, promoting vasogenic cerebral edema and non-cardiogenic pulmonary edema, which are responsible for most of the morbidity and mortality in severe cases. To date, the cellular and molecular mechanisms by which SFG Rickettsia increase EC permeability are largely unknown. In the present study we used atomic force microscopy (AFM) to study the interactive forces between vascular endothelial (VE)-cadherin and human cerebral microvascular EC infected with R. montanensis, which is genetically similar to R. rickettsii and R. conorii, and displays a similar ability to invade cells, but is non-pathogenic and can be experimentally manipulated under Biosafety Level 2 (BSL2) conditions. We found that infected ECs show a significant decrease in VE-cadherin-EC interactions. In addition, we applied immunofluorescent staining, immunoprecipitation phosphorylation assay, and an in vitro endothelial permeability assay to study the biochemical mechanisms that may participate in the enhanced vascular permeability as an underlying pathologic alteration of SFG rickettsial infection. A major finding is that infection of R. montanensis significantly activated tyrosine phosphorylation of VE-cadherin beginning at 48 hr and reaching a peak at 72 hr p.i. In vitro permeability assay showed an enhanced microvascular permeability at 72 hr p.i. On the other hand, AFM experiments showed a dramatic reduction in VE-cadherin-EC interactive forces at 48 hr p.i. We conclude that upon infection by SFG rickettsiae, phosphorylation of VE-cadherin directly attenuates homophilic protein–protein interactions at the endothelial adherens junctions, and may lead to endothelial paracellular barrier dysfunction causing microvascular hyperpermeability. These new approaches should prove useful in characterizing the antigenically related SFG rickettsiae R. conorii and R. rickettsii in a BSL3 environment. Future studies may lead to the development of new therapeutic strategies to inhibit the VE-cadherin-associated microvascular hyperpermeability in SFG rickettsioses