Efficacy and Safety of a Nonanimal Stabilized Hyaluronic Acid/Dextranomer in Improving Fecal Incontinence: A Prospective, Single-Arm, Multicenter, Clinical Study With 36-Month Follow-up.

BACKGROUND: Fecal incontinence affects 7% to 12% of the US adult population, causing social, financial, and quality of life burdens. OBJECTIVE: The primary aim of this study was to evaluate the efficacy and safety of nonanimal stabilized hyaluronic acid/dextranomer through 36 months as a condition of postmarket approval application. DESIGN: This was a prospective, single-arm, multicenter, observational Food and Drug Administration-mandated postapproval clinical study. SETTINGS: This study was designed and executed by participating centers in 18 hospitals and colorectal health clinics in coordination with the Food and Drug Administration and the study sponsor. PATIENTS: A total of 283 subjects who previously failed conservative therapy were enrolled across 18 US sites. INTERVENTIONS: Participants received 1 to 2 nonanimal stabilized hyaluronic acid/dextranomer treatments. The first treatment occurred within 30 days of baseline, and a second treatment was administered 1 to 3 months after initial treatment if determined necessary by the physician. Subjects were followed through 7 visits over 36 months after last treatment. MAIN OUTCOME MEASURES: Efficacy (as specified by the Food and Drug Administration) was measured as a fecal incontinence reintervention rate of <50% at 36 months. Reintervention included nonanimal stabilized hyaluronic acid/dextranomer re-treatment, surgical interventions, and physical therapy. Safety was measured by device-related adverse events. Secondary end points included Fecal Incontinence Quality of Life Scale and Cleveland Clinic Florida Fecal Incontinence Score. RESULTS: Using a Bayesian estimate, the reintervention rate of the intention-to-treat population (n = 283) was 18.9% (95% CI, 14.0-24.4) at 36 months. At 36 months, the reintervention rate for subjects with complete data (n = 192) was 20.8% (95% CI, 15.1-26.6). Significant improvement ( p < 0.0001) was noted across the Cleveland Clinic Florida Fecal Incontinence Score and Fecal Incontinence Quality of Life subscales at 36 months. Ninety-two device-related adverse events were reported by 15.2% of enrolled patients; most were GI disorders and resolved quickly. There were no serious adverse events. LIMITATIONS: Limitations of the study included a 32% attrition rate and homogeneous patient population (91.8% white; 85.5% female), possibly limiting generalizability. CONCLUSIONS: Nonanimal stabilized hyaluronic acid/dextranomer demonstrated clinically significant, sustained improvement in symptoms and quality of life for fecal incontinence patients without the occurrence of any serious adverse events. See Video Abstract at http://links.lww.com/DCR/B890 . REGISTRATION: ClinicalTrials.gov ; Unique identifier: NCT01647906. EFICACIA Y SEGURIDAD DE UN CIDO HIALURNICO/ DEXTRANMERO ESTABILIZADO DE ORGEN NO ANIMAL PARA MEJORAR LA INCONTINENCIA FECAL UN ESTUDIO CLNICO PROSPECTIVO, MULTICNTRICO Y DE UN SOLO BRAZO CON SEGUIMIENTO DE MESES: ANTECEDENTES:La incontinencia fecal afecta entre el 7 y el 12% de la población adulta de los EE. UU. Y genera cargas sociales, económicas y de calidad de vida.OBJETIVO:Los objetivos principales de este estudio fueron evaluar la eficacia y seguridad del ácido hialurónico/ dextranómero estabilizado de origen no animal durante 36 meses como condición para la solicitud de aprobación posterior a la comercialización.DISEÑO:Este fue un estudio clínico prospectivo, observacional, de un solo brazo, multicéntrico, ordenado por la FDA después de la aprobación.AJUSTES:Este estudio fue diseñado por los investigadores participantes, la FDA y el patrocinador del estudio que gestionó la recopilación de datos.PACIENTES:Un total de 283 sujetos en quienes previamente falló la terapia conservadora se inscribieron en el estudio prospectivo de un solo brazo en 18 sedes de EE. UU. (NCT01647906).INTERVENCIONES:Los participantes recibieron 1-2 tratamientos con ácido hialurónico/ dextranómero estabilizado no animal. El primer tratamiento se dio dentro de los 30 días posteriores al inicio, mientras que un segundo tratamiento se administró 1-3 meses después del tratamiento inicial si el médico lo determinaba necesario. Los sujetos fueron seguidos durante 7 visitas durante 36 meses después del último tratamiento.PRINCIPALES MEDIDAS DE RESULTADO:La eficacia (según especificado por la FDA) se midió como una tasa de reintervención de incontinencia fecal de <50% a los 36 meses. La reintervención incluyó retratamiento con ácido hialurónico/ dextranómero estabilizado no animal, intervenciones quirúrgicas y fisioterapia. La seguridad se midió mediante los eventos adversos relacionados con tratamiento. Los criterios de valoración secundarios incluyeron la escala de calidad de vida de incontinencia fecal y la puntuación de incontinencia fecal de Cleveland Clinic Florida.RESULTADOS:Utilizando una estimación bayesiana, la tasa de reintervención de la población por intención de tratar (n = 283) fue del 18.9% (IC del 95%: 14.0%, 24.4%) a los 36 meses. A los 36 meses, la tasa de reintervención para los sujetos con datos completos (n = 192) fue del 20.8% (IC del 95%: 15.1%, 26.6%). Se observó una mejora significativa (p <0.0001) en las subescalas de la puntuación de incontinencia fecal de la Cleveland Clinic Florida y de la calidad de vida de la incontinencia fecal a los 36 meses. El 15.2% de los pacientes inscritos informaron 92 eventos adversos relacionados con el tratmiento; la mayoría eran trastornos gastrointestinales y se resolvieron rápidamente. No hubo eventos adversos graves.LIMITACIONES:Las limitaciones incluyen una tasa de deserción del 32% y una población de pacientes homogénea (91.8% blancos, 85.5% mujeres), lo que posiblemente limite la generalización.CONCLUSIÓNES:El ácido hialurónico/ dextranómero estabilizado de origen no animal demostró una mejora sostenida y clínicamente significativa de los síntomas y la calidad de vida de los pacientes con incontinencia fecal, sin que se produjeran efectos adversos graves. Consulte el Video Resumen en http://links.lww.com/DCR/B890 . ( Traducción-Dr. Jorge Silva Velazco )Registro: ClinicalTrials.gov número NCT01647906.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Global adherence to pharmacotherapeutic treatment in patients with multiple sclerosis / Adherencia global al tratamiento farmacoterapéutico en pacientes con esclerosis múltiple

Objective: To measure the indirect adherence of patients with multiple sclerosis (MS) to their pharmacological treatments, comparing medication for the disease itself with the other concomitant treatments that have been chronically prescribed.Methods: A cross-sectional, descriptive (November 2018) study at the Pharmacy Department of a spanish secondary hospital in Valencian Community. Study population is all those patients diagnosed with MS in its different variants, who are being treated with hospital dispensing drugs for a minimum of six months at the time of the study. The variable evaluated was the percentage of adherence of patients to their medication, which has been measured as the ratio between the doses of prescribed drugs and those dispensed; considering adherent to all patients with a percentage equal to or higher than 80%.Results: The study included 86 patients from the Pharmacy External Outpatient Unit. The average exposure time to drugs was 198.7±27.9 days, where the adherence to treatment of multiple sclerosis was 98.1±6.6% and that of the rest of the chronic medication concomitant 92.8±19.5%.Conclusions: Adherence to pharmacological treatments in this population has been very high. Patients have shown greater adherence to drugs dispensed at Pharmacy External Outpatient Unit, possibly because they consider the rest of medication less important and/or to treat milder comorbidities or pathologies. (AU)

Objetivos: Evaluar la adherencia indirecta de los pacientes con esclerosis múltiple (EM) a sus tratamientos farmacológicos, comparando la medicación para esta enfermedad entre los diferentes fármacos, y con el resto de tratamientos concomitantes prescritos por el médico de manera crónica.Material y métodos: Estudio descriptivo transversal (noviembre 2018) en el Servicio de Farmacia de un hospital secundario español de la Comunidad Valenciana. La población de estudio son todos aquellos pacientes diagnosticados con EM en sus diferentes variantes, que están siendo tratados con medicamentos dispensados desde el hospital, durante un periodo mínimo de seis meses. La variable evaluada fue el porcentaje de adherencia de los pacientes a su medicación, que se midió como la relación entre las dosis de los medicamentos prescritos y aquellos dispensados; considerando adherente a todos los pacientes con un porcentaje igual o superior al 80%.Resultados: Se incluyó a 86 pacientes desde la Unidad de Pacientes Externos del Servicio de Farmacia. El tiempo promedio de exposición a los fármacos para la EM fue de 198,7±27,9 días, observando una adherencia al tratamiento de 98,1±6,6% y una adherencia al resto de la medicación crónica concomitante de 92,8±19,5%.Conclusiones: La adherencia a los tratamientos farmacológicos en esta población ha sido muy alta. Los pacientes han mostrado una mayor adherencia a los medicamentos dispensados en la Unidad de Pacientes Externos del Servicio de Farmacia, posiblemente porque consideran que el resto de la medicación es menos importante y/o para tratar comorbilidades o patologías más leves. (AU)

Association Among Noncalcified Coronary Burden, Fractional Flow Reserve, and Myocardial Injury in Psoriasis.

Background Myocardial infarction and premature death have been observed in patients with psoriasis. Although inflammation-driven accelerated atherosclerosis has been proposed as a mechanism, the relationship between subclinical noncalcified coronary burden (NCB), functional coronary flow impairment, and myocardial injury is unclear. Methods and Results In an ongoing longitudinal cohort study, 202 consecutive patients with psoriasis (168 at 1 year) underwent coronary computed tomography angiography to identify coronary plaque, quantify NCB, and calculate coronary fractional flow reserve by computed tomography. Serum high-sensitivity troponin-T (hs-cTn-T) was measured using a fifth-generation assay. Overall, patients were middle-aged, predominantly male, and low cardiovascular risk. A higher than median NCB associated with a positive hs-cTn-T (fully adjusted model [odds ratio (OR), 1.72; 95% CI, 1.10-2.69, P=0.018]) at baseline. Additionally, patients with a higher than median baseline NCB had higher odds of positive hs-cTn-T at 1 year in fully adjusted analyses (adjusted OR, 2.36; 95% CI, 1.47-3.79, P<0.001). Higher NCB was associated with a higher frequency of fractional flow reserve by computed tomography ≤0.80 (36.11% versus 25.11%, Pearson χ2=6.84, P=0.009, unadjusted OR, 2.09; 95% CI, 1.36-3.22, P<0.001) and higher frequency of a positive hs-cTn-T (54.36% versus 27.54%, Pearson χ2=32.23, P<0.001) in adjusted models (OR, 2.63; 95% CI, 1.56-4.42, P<0.001). Conclusions NCB was associated with hs-cTn-T at baseline as well as at 1 year. Furthermore, patients with high NCB had higher prevalence of fractional flow reserve by computed tomography ≤0.80 and a >2- fold higher odds of positive hs-cTn-T. These findings underscore the importance of early vascular disease in driving myocardial injury, and support conduct of myocardial perfusion studies to better understand these findings.

Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (ß = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (ß = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (ß = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.

Treatment of Psoriasis With Biologic Therapy Is Associated With Improvement of Coronary Artery Plaque Lipid-Rich Necrotic Core: Results From a Prospective, Observational Study.

BACKGROUND: Lipid-rich necrotic core (LRNC), a high-risk coronary plaque feature assessed by coronary computed tomography angiography, is associated with increased risk of future cardiovascular events in patients with subclinical, nonobstructive coronary artery disease. Psoriasis is a chronic inflammatory condition that is associated with increased prevalence of high-risk coronary plaque and risk of cardiovascular events. This study characterized LRNC in psoriasis and how LRNC modulates in response to biologic therapy. METHODS: Consecutive biologic naïve psoriasis patients (n=209) underwent coronary computed tomography angiography at baseline and 1-year to assess changes in LRNC using a novel histopathologically validated software (vascuCAP Elucid Bioimaging, Boston, MA) before and after biologic therapy over 1 year. RESULTS: Study participants were middle-aged, predominantly male with similar cardiometabolic and psoriasis status between treatment groups. In all participants at baseline, LRNC was associated with Framingham risk score (ß [standardized ß]=0.12 [95% CI, 0.00-0.15]; P=0.045), and psoriasis severity (ß=0.13 [95% CI, 0.01-0.26]; P=0.029). At 1-year, participants receiving biologic therapy had a reduction in LRNC (mm2; 3.12 [1.99-4.66] versus 2.97 [1.84-4.35]; P=0.028), while those who did not receive biologic therapy over 1 year demonstrated no significant change with nominally higher LRNC (3.12 [1.82-4.60] versus 3.34 [2.04-4.74]; P=0.06). The change in LRNC was significant compared with that of the nonbiologic treated group (ΔLRNC, -0.22 mm2 versus 0.14 mm2, P=0.004) and remained significant after adjusting for cardiovascular risk factors and psoriasis severity (ß=-0.09 [95% CI, -0.01 to -0.18]; P=0.033). CONCLUSIONS: LRNC was associated with psoriasis severity and cardiovascular risk factors in psoriasis. Additionally, there was favorable modification of LRNC in those on biologic therapy. This study provides evidence of potential reduction in LRNC with treatment of systemic inflammation. Larger, longer follow-up prospective studies should be conducted to understand how changes in LRNC may translate into a reduction in future cardiovascular events in psoriasis.

Relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease in psoriasis: Findings from a longitudinal observational cohort study.

BACKGROUND AND AIMS: Amygdalar 18F-fluorodeoxyglucose (FDG) uptake represents chronic stress-related neural activity and associates with coronary artery disease by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic physiological stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease, we studied the association between amygdalar FDG uptake, allostatic load score and subclinical non-calcified coronary artery burden (NCB) in psoriasis. METHODS: Consecutive psoriasis patients (n = 275 at baseline and n = 205 at one-year follow-up) underwent CCTA for assessment of NCB (QAngio, Medis). Amygdalar FDG uptake and allostatic load score were determined using established methods. RESULTS: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity. Allostatic load score associated with psoriasis severity (ß = 0.17, p = 0.01), GlycA (a systemic marker of inflammation, ß = 0.49, p < 0.001), amygdalar activity (ß = 0.30, p < 0.001), and NCB (ß = 0.39; p < 0.001). Moreover, NCB associated with amygdalar activity in participants with high allostatic load score (ß = 0.27; p < 0.001) but not in those with low allostatic load score (ß = 0.07; p = 0.34). Finally, in patients with an improvement in allostatic load score at one year, there was an 8% reduction in amygdalar FDG uptake (p < 0.001) and a 6% reduction in NCB (p = 0.02). CONCLUSIONS: In psoriasis, allostatic load score represents physiological dysregulation and may capture pathways by which chronic stress-related neural activity associates with coronary artery disease, emphasizing the need to further study stress-induced physiological dysregulation in inflammatory disease states.

Queratoplastia endotelial de la membrana de Descemet y biomecánica corneal / Descemet membrane endothelial keratoplasty and corneal biomechanics

OBJETIVO: Estudiar el comportamiento de las propiedades biomecánicas de la córnea en la DMEK (Descemet membrane endothelial keratoplasty). MÉTODO: Estudio observacional longitudinal prospectivo; 21 ojos pre- y post-DMEK. Seguimiento de 3 meses con el analizador Scheimpflug dinámico (Corvis ST, Oculus; Wetzlar, Alemania). Se midieron los siguientes parámetros: PIOnc: presión intraocular (PIO) no corregida, PIOb: PIO corregida mediante biomecánica, amplitud de deflexión máxima (DefA), CCT: paquimetría corneal central, velocidad de aplanación 1 y 2, peak distance, HC deformation amplitude: amplitud de deformación en máxima concavidad, radio cóncavo inverso integrado, DAR 1 y 2: amplitud de deformación a 1mm y 2mm del ápex corneal, respectivamente. ARTh: relación paquimétrica de Ambrosio, SP1: parámetro de rigidez, CBI: corvis biomechanical index y el radio máximo inverso. Se realizaron las medidas de forma preoperatoria y postoperatoria con un seguimiento de 3 meses y se compararon con una prueba t para muestras emparejada. RESULTADOS: Se produjo una disminución significativa de la PIOnc de 1,54 ± 3 mmHg (p < 0,05), aumento significativo de la PIOb posquirúrgica de 3,79 ± 3,18 mmHg (p < 0,001), una disminución significativa paquimétrica de 164,4 ± 91,35μm (p < 0,001) tras la intervención. Todos los parámetros dinámicos del analizador Scheimpflug cambiaron significativamente después de la cirugía (p < 0,05), excepto las variable ARTh y CBI. CONCLUSIONES: Las variables indican un descenso en la resistencia de la córnea post-DMEK, con un aumento de la PIOb, al menos los primeros 3 meses tras la cirugía. Este hallazgo es especialmente relevante en el seguimiento de los pacientes con coexistencia de glaucoma

OBJECTIVE: To study the behaviour of the biomechanical properties of the cornea in DMEK (Descemet membrane endothelial keratoplasty). METHOD: Prospective longitudinal observational study. 21 pre and post-DMEK eyes. 3-month follow-up with the dynamic Scheimpflug Analyzer (Corvis ST, Oculus; Wetzlar, Germany). The following parameters were measured: IOPnc: non-corrected intraocular pressure (IOP), IOPb: IOP corrected by biomechanics, maximum deflection amplitude (DefA), CCT: central corneal pachymetry, flattening speed 1 and 2, peak distance, HC deformation amplitude: deformation amplitude in maximum concavity, integrated inverse concave radius, DAR 1 and 2: deformation amplitude at 1mm and 2mm from the corneal apex, respectively. ARTh: Ambrosial pachymetric ratio, SP1: stiffness parameter, CBI: Corvis Biomechanical index and the maximum inverse radius. Pre-operative and post-operative measurements were performed with a 3-month follow-up and compared with a paired sample t-test. RESULTS: There was a significant decrease in the IOPnc of 1.54 ± 3 mmHg (p < 0.05), a significant increase in the post-surgical IOPb of 3.79 ± 3.18 mmHg (p < 0.001), a significant pachymetric decrease of 164.4 ± 91.35 μm (p < 0.001) after the intervention. All dynamic parameters of the Scheimpflug analyzer changed significantly after surgery (p < 0.05), except the ARTh and IWC variables. CONCLUSIONS: Variables indicate a decrease in corneal strength post-DMEK, with an increase in IOPb, at least the first 3 months after surgery. This finding is especially relevant in the follow-up of patients with coexisting glaucoma

Descemet membrane endothelial keratoplasty and corneal biomechanics. / Queratoplastia endotelial de la membrana de Descemet y biomecánica corneal.

OBJECTIVE: To study the behaviour of the biomechanical properties of the cornea in DMEK (Descemet membrane endothelial keratoplasty). METHOD: Prospective longitudinal observational study. 21 pre and post-DMEK eyes. 3-month follow-up with the dynamic Scheimpflug Analyzer (Corvis ST, Oculus; Wetzlar, Germany). The following parameters were measured: IOPnc: non-corrected intraocular pressure (IOP), IOPb: IOP corrected by biomechanics, maximum deflection amplitude (DefA), CCT: central corneal pachymetry, flattening speed 1 and 2, peak distance, HC deformation amplitude: deformation amplitude in maximum concavity, integrated inverse concave radius, DAR 1 and 2: deformation amplitude at 1mm and 2mm from the corneal apex, respectively. ARTh: Ambrosial pachymetric ratio, SP1: stiffness parameter, CBI: Corvis Biomechanical index and the maximum inverse radius. Pre-operative and post-operative measurements were performed with a 3-month follow-up and compared with a paired sample t-test. RESULTS: There was a significant decrease in the IOPnc of 1.54±3mmHg (p<0.05), a significant increase in the post-surgical IOPb of 3.79±3.18mmHg (p<0.001), a significant pachymetric decrease of 164.4±91.35µm (p<0.001) after the intervention. All dynamic parameters of the Scheimpflug analyzer changed significantly after surgery (p<0.05), except the ARTh and IWC variables. CONCLUSIONS: Variables indicate a decrease in corneal strength post-DMEK, with an increase in IOPb, at least the first 3 months after surgery. This finding is especially relevant in the follow-up of patients with coexisting glaucoma.

PET Scan with Fludeoxyglucose/Computed Tomography in Low-Grade Vascular Inflammation.

Fluorodeoxyglucose-PET/computed tomography combines the high sensitivity of PET with the excellent spatial resolution provided by computed tomography, making it a potentially powerful tool for capturing and quantifying early vascular diseases. Patients with chronic inflammatory states have an increased risk of cardiovascular events; there is also increased vascular fluorodeoxyglucose uptake seen compared with healthy controls. This review examines the use of fluorodeoxyglucose-PET/computed tomography in assessing low-grade vascular inflammation in chronic inflammation and then reviews fluorodeoxyglucose-PET/computed tomography as a tool in monitoring the efficacy of various treatments known to modulate cardiovascular disease.

Accumulation of Pericardial Fat Is Associated With Alterations in Heart Rate Variability Patterns in Hypercholesterolemic Pigs.

BACKGROUND: Heart rate variability (HRV) and pulse rate variability are indices of autonomic cardiac modulation. Increased pericardial fat is associated with worse cardiovascular outcomes. We hypothesized that progressive increases in pericardial fat volume and inflammation prospectively dampen HRV in hypercholesterolemic pigs. METHODS: WT (wild type) or PCSK9 (proprotein convertase subtilisin-like/kexin type-9) gain-of-function Ossabaw mini-pigs were studied in vivo before and after 3 and 6 months of a normal diet (WT-normal diet, n=4; PCSK9-normal diet, n=6) or high-fat diet (HFD; WT-HFD, n=3; PCSK9-HFD, n=6). The arterial pulse waveform was obtained from an arterial telemetry transmitter to analyze HRV indices, including SD (SD of all pulse-to-pulse intervals over a single 5-minute period), root mean square of successive differences, proportion >50 ms of normal-to-normal R-R intervals, and the calculated ratio of low-to-high frequency distributions (low-frequency power/high-frequency power). Pericardial fat volumes were evaluated using multidetector computed tomography and its inflammation by gene expression of TNF (tumor necrosis factor)-α. Plasma lipid panel and norepinephrine level were also measured. RESULTS: At diet completion, hypercholesterolemic PCSK9-HFD had significantly (P<0.05 versus baseline) depressed HRV (SD of all pulse-to-pulse intervals over a single 5-minute period, root mean square of successive differences, proportion >50 ms, high-frequency power, low-frequency power), and both HFD groups had higher sympathovagal balance (SD of all pulse-to-pulse intervals over a single 5-minute period/root mean square of successive differences, low-frequency power/high-frequency power) compared with normal diet. Pericardial fat volumes and LDL (low-density lipoprotein) cholesterol concentrations correlated inversely with HRV and directly with sympathovagal balance, while sympathovagal balance correlated directly with plasma norepinephrine. Pericardial fat TNF-α expression was upregulated in PCSK9-HFD, colocalized with nerve fibers, and correlated inversely with root mean square of successive differences and proportion >50 ms. CONCLUSIONS: Progressive pericardial fat expansion and inflammation are associated with a fall in HRV in Ossabaw mini-pigs, implying aggravated autonomic imbalance. Hence, pericardial fat accumulation is associated with alterations in HRV and the autonomic nervous system. Visual Overview: A visual overview is available for this article.

Skin sympathetic nerve activity as a biomarker for syncopal episodes during a tilt table test.

BACKGROUND: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes. OBJECTIVE: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope. METHODS: We studied 50 patients with a history of neurocardiogenic syncope undergoing a TTT. The recorded signals were band-pass filtered at 500-1000 Hz to analyze nerve activity. RESULTS: The average SKNA (aSKNA) value at baseline was 1.38 ± 0.38 µV in patients without syncope and 1.42 ± 0.52 µV in patients with syncope (P = .77). On upright tilt, aSKNA was 1.34 ± 0.40 µV in patients who did not have syncope and 1.39 ± 0.43 µV in patients who had syncope (P = .65). In all 14 patients with syncope, there was a surge of SKNA before an initial increase in heart rate followed by bradycardia, hypotension, and syncope. The peak aSKNA immediately (<1 minute) before syncope was significantly higher than baseline aSKNA (2.63 ± 1.22 vs 1.39 ± 0.43 µV; P = .0005). After syncope, patients were immediately placed in the supine position and aSKNA dropped significantly to 1.26 ± 0.43 µV; (P = .0004). The heart rate variability during the TTT shows a significant increase in parasympathetic tone during syncope (low-frequency/high-frequency ratio: 7.15 vs 2.21; P = .04). CONCLUSION: Patients with syncope do not have elevated sympathetic tone at baseline or during the TTT except immediately before syncope when there is a transient surge of SKNA followed by sympathetic withdrawal along with parasympathetic surge.

Application of Non-invasive Imaging in Inflammatory Disease Conditions to Evaluate Subclinical Coronary Artery Disease.

PURPOSE OF REVIEW: Traditional risk models, such as the Framingham risk score, fail to capture the increased cardiovascular disease risk seen in patients with chronic inflammatory diseases. This review will cover imaging modalities and their emerging applications in assessing subclinical cardiovascular disease for both research and clinical care in patients with chronic inflammatory diseases. RECENT FINDINGS: Multiple imaging modalities have been studied to assess for subclinical cardiovascular disease via functional/physiologic, inflammatory, and anatomic assessment in patients with chronic inflammatory diseases. The use of imaging to evaluate subclinical cardiovascular disease in patients with chronic inflammatory diseases has the potential to capture early sub-clinical atherosclerosis, to improve risk stratification of future cardiovascular events, and to guide effective disease management.

Interfraction Variation and Dosimetric Changes in Patients With Cervical Cancer Treated With Intracavitary Brachytherapy.

PURPOSE: Intracavitary brachytherapy is integral in the treatment of cervical cancer. Because of interfraction variation, the current standard is replanning with every fraction. This study aimed to determine whether there was a difference in relative dosimetry if the source position and dwell time of the first fraction were applied to subsequent fractions. MATERIALS AND METHODS: The authors performed a retrospective review of charts and films from 2007 to 2012. Eligible cases were patients with cervical cancer treated with brachytherapy with the same dose prescription to point A. Replanning was done on the first set of orthogonal plates. Source position and dwell time were subsequently applied to the remaining fractions using actual films. RESULTS: Twenty-nine patients were included in this study. The results showed that cervical, rectal, and bladder dose between the actual plan and the hypothetical plan were not statistically different. In the hypothetical plan, the source activity and dwell time of the first plan were applied to the orthogonal films of the subsequent fractions and showed no significant difference in all dose points. CONCLUSION: The results of this study showed proof of concept of the safety of using the source position and dwell time of the first plan for subsequent fractions. Until further studies are performed (also using three-dimensional planning software), the concept should be considered investigational because of the small sample size of the study. Until such research is performed, it is still strongly recommended that replanning be performed with every fraction whenever it is feasible.

Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs) are innate immune cells with high antiviral activity triggered by Toll-like receptor 7 (TLR-7) and TLR-9 stimulation. Moreover, they are important mediators between innate and adaptive immunity. Although nowadays there is available an effective therapeutic arsenal against hepatitis C virus (HCV), a protective vaccine is not available. We have analyzed the pDCs' response to HCV infection in a hepatitis C virus (HCV)-Huh7.5 virus-cell system, which allows completion of the virus infectious cycle. pDCs were cocultured following human immunodeficiency virus (HIV) aldrithiol-2 (AT-2 [TLR-7 agonist]) inactivation and CpG (TLR-9 agonist) stimulation. We employed three virus derivatives-wild-type Jc1, interferon (IFN)-resistant virus IR, and high-replicative-fitness virus P100-in order to explore additional IFN-α-related virus inhibition mechanisms. pDCs inhibited HCV infectivity and replication and produced IFN-α. After TLR-7 and TLR-9 stimulation, inhibition of infectivity and IFN-α production by pDCs were enhanced. TLR-7 stimulation drove higher TNF-related apoptosis-inducing ligand (TRAIL) expression in pDCs. Additionally, TLR-7- and TLR-9-stimulated pDCs exhibited a mature phenotype, improving the antigen presentation and lymph node homing-related markers. In conclusion, pDCs could serve as a drug target against HCV in order to improve antiviral activity and as an enhancer of viral immunization.IMPORTANCE We implemented a coculture system of pDCs with HCV-infected hepatoma cell line, Huh7.5. We used three HCV derivatives in order to gain insight into pDCs' behavior against HCV and associated antiviral mechanisms. The results with this cell coculture system support the capacity of pDCs to inhibit HCV replication and infectivity mainly via IFN-α, but also through additional mechanisms associated with pDC maturation. We provided evidence that TLR agonists can enhance antiviral pDCs' function and can induce phenotypic changes that may facilitate the interplay with other immune cells. These findings suggest the possibility of including TLR agonists in the strategies of HCV vaccine development.

Prognostic markers for colorectal cancer: estimating ploidy and stroma.

Background: We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). Patients and methods: DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Results: Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001]. Conclusion: A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

Características de los protocolos de investigación presentados por los cursantes de la asignatura "Metodología de la Investigación en Enfermería", Facultad de Medicina, UNNE. Período 2005-2015 / Characteristics of the research protocols presented by the students of the subject "Research Methodology in Nursing ", Faculty of Medicine, UNNE. Period 2005-2015

La calidad de atención y del cuidado enfermero, depende en gran medida de hacer a la investigación uno de los pilares más importantes de la enfermería como ciencia. El objetivo de este trabajo fue determinar las características de los protocolos de investigación presentados por los cursantes de la asignatura de Metodología de la Investigación en Enfermería de la carrera de Licenciatura en Enfermería de la Universidad Nacional del Nordeste durante los años 2005 al 2015. Se realizó un estudio de tipo cuantitativo, descriptivo, retrospectivo y transversal, y se consultaron los protocolos archivados en la biblioteca de dicha Facultad. Se trabajó con 230 protocolos. El 100% de los trabajos eran de tipo cuantitativos y de estos el 65% descriptivos y 35% analíticos. El 94% de los trabajos fueron de tipo transversales superando ampliamente a los longitudinales. En cuanto al área temática las principales fueron la clínica y la salud pública. El 67% de los protocolos fueron retrospectivos y el 33% prospectivo. Según el contexto de realización de los estudios se observó que la mayoría de los trabajos fueron realizados en instituciones del segundo y tercer nivel. Las investigaciones que se publicaron en revistas con referato ascendieron a 12 lo que representó solo el 5% del total. El promedio de protocolos por año fue de 20, con un valor mínimo de 5 en el 2005 y un valor máximo de 51 en el 2015. Los resultados mostraron buena productividad en los futuros licenciados en enfermería, con un predominio de estudios de tipo cuantitativo, principalmente abocados a la clínica, aunque se evidencio escasa publicación de los protocolos de investigación.

The quality of care and nursing care depends of a large extent on making research one of the most important pillars of nursing as a science. The objective of this work was to determine the characteristics of the research protocols presented by the students of the Nursing Research Methodology course of the Bachelor's degree in Nursing of the National University of the Northeast during the years 2005 to 2015. It was carried out a quantitative, descriptive, retrospective and transversal study, and the protocols filed in the library of said Faculty were consulted. We worked with 230 protocols. 100% of the works were of quantitative type and of these 65% descriptive and 35% analytical. 94% of the works were of transversal type surpassing extensively to the longitudinal ones. As for the thematic area the main ones were the clinic and the public health. 67% of the protocols were retrospective and 33% prospective. According to the context of the studies, it was observed most of the work was done in institutions of the second and third level. Research published in peer-reviewed journals amounted to 12 which represented only 5% of the total. The average number of protocols per year was 20, with a minimum value of 5 in 2005 and a maximum value of 51 in 2015. The results showed good productivity in future nursing graduates, with a predominance of quantitative studies, mainly in the clinical setting, although there was little publication of the research protocols. Key words: research, research methodology, nursing, students

How Can We Help a Patient With a Small Failing Bioprosthesis?: An In Vitro Case Study.

OBJECTIVES: The aim of this study was to investigate the hemodynamic performance of a transcatheter heart valve (THV) deployed at different valve-in-valve positions in an in vitro model using a small surgical bioprosthesis. BACKGROUND: Patients at high surgical risk with failing 19-mm surgical aortic bioprostheses are not candidates for valve-in-valve transcatheter aortic valve replacement, because of risk for high transvalvular pressure gradients (TVPGs) and patient-prosthesis mismatch. METHODS: A 19-mm stented aortic bioprosthesis was mounted into the aortic chamber of a pulse duplicator, and a 23-mm low-profile balloon-expandable THV was deployed (valve-in-valve) in 4 positions: normal (bottom of the THV stent aligned with the bottom of the surgical bioprosthesis sewing ring) and 3, 6, and 8 mm above the normal position. Under controlled hemodynamic status, the effect of these THV positions on valve performance (mean TVPG, geometric orifice area, and effective orifice area), thrombotic potential (sinus shear stress), and migration risk (pullout force and embolization flow rate) were assessed. RESULTS: Compared with normal implantation, a progressive reduction of mean TVPG was observed with each supra-annular THV position (normal: 33.10 mm Hg; 3 mm: 24.69 mm Hg; 6 mm: 19.16 mm Hg; and 8 mm: 12.98 mm Hg; p < 0.001). Simultaneously, we observed increases in geometric orifice area (normal: 0.83 cm(2); 8 mm: 1.60 cm(2); p < 0.001) and effective orifice area (normal: 0.80 cm(2); 8 mm: 1.28 cm(2); p < 0.001) and reductions in sinus shear stresses (normal: 153 dyne/cm(2); 8 mm: 40 dyne/cm(2); p < 0.001), pullout forces (normal: 1.55 N; 8 mm: 0.68 N; p < 0.05), and embolization flow rates (normal: 32.91 l/min; 8 mm: 26.06 l/min; p < 0.01). CONCLUSIONS: Supra-annular implantation of a THV in a small surgical bioprosthesis reduces mean TVPG but may increase the risk for leaflet thrombosis and valve migration. A 3- to 6-mm supra-annular deployment could be an optimal position in these cases.

Trombosis aguda de stent y dilatación transitoria ventricular izquierda inversa tras la realización de una tomografía computarizada de emisión monofotónica de esfuerzo / Acute stent thrombosis and reverse transient left ventricular dilatation after performing a single-photon emission computed tomography myocardial perfusion

Paciente de 63 años con antecedentes de implantación de un stent en la descendente anterior 3meses antes. Se le practicó una gated-SPECT de perfusión miocárdica de esfuerzo al presentar síntomas vegetativos. Durante la adquisición de las imágenes de reposo presentó dolor precordial y elevación del segmento ST por lo que se realizó un cateterismo cardiaco urgente que evidenció una trombosis aguda intra-stent. Las imágenes de perfusión correspondientes al reposo demostraron un defecto de perfusión anterior y apical, más intenso y extenso que en las imágenes de esfuerzo, con una llamativa dilatación ventricular izquierda y caída de la fracción de eyección, en relación con el fenómeno de isquemia aguda. El ejercicio intenso se asocia con una activación transitoria del sistema de coagulación y cambios hemodinámicos que pueden inducir trombosis, especialmente en stents coronarios recientemente implantados y probablemente no completamente endotelizados (AU)

A 63-year-old male patient with a history of stent implantation in the left anterior descending three months before. Due to the presentation of vegetative symptoms, he was referred for gated-SPECT myocardial perfusion. During acquisition of the resting images he presented chest pain and ST segment elevation, so that urgent cardiac catheterization was performed, showing stent thrombosis. Rest perfusion imaging showed a defect in anterior and apical perfusion, more severe and extensive than in the stress images, with striking left ventricular dilatation and a fall in the ejection fraction related to the acute ischemia phenomenon. Intense exercise is associated with a transient activation of the coagulation system and hemodynamic changes that might induce thrombosis, especially in recently implanted coronary stents that probably still have not become completely endothelialized (AU)