F. Roth

Comparison of MELD, Child-Pugh, and Emory model for the prediction of survival in patients undergoing transjugular intrahepatic portosystemic shunting

OBJECTIVES:Recently, new prognostic models (Model for End-Stage Liver Disease [MELD model] and Emory score) were proposed for the prediction of survival in transjugular intrahepatic portosystemic shunt (TIPS) patients. Although the MELD model is considered to be superior and has consecutively been applied to priority listing for liver transplantation, these models have never been directly compared in terms of long-term prognosis. We therefore compared the prognostic accuracy of the different models, including the Child-Pugh score, in an unselected cohort of TIPS patients followed long-term.METHODS:Baseline risk scores for 162 unselected consecutive TIPS patients followed until death (n = 81), liver transplantation, or end of observation (n = 81) (mean follow-up 30.7 ± 26.4 months) were calculated, and respective concordance- (c-)statistics for the predictive accuracy of 3-, 12-, and 36-month survival for the three models were compared statistically.RESULTS:All three models predicted short-term (3-month) survival with similar accuracy. The MELD model generated the best c-statistics for both 12-month (c-statistic 0.73, 95% CI = 0.64–0.82) and 36-month survival (c-statistic 0.74, 95% CI = 0.64–0.84). The predictive accuracy of the Emory score was significantly lower (c-statistic for 12-month survival: 0.60, 95% CI = 0.52–0.68, p = 0.012 vs MELD). In the statistical comparison of the MELD and the Child-Pugh model, only a trend favoring MELD for the prediction of 1-yr survival in patients with intestinal bleeding could be observed (MELD: c-statistic 0.78, 95% CI = 0.67–0.89; Child-Pugh: c-statistic 0.67, 95% CI = 0.55–0.80, p = 0.059).CONCLUSIONS:The MELD model is superior to the Emory score but only slightly superior to the Child-Pugh classification for the prediction of long-term survival in TIPS patients.

Keypathophysiologic pathways in age-related macular disease.

PurposeTo review current knowledge of key pathogenetic pathways in age-related macular disease (AMD).MethodsExperimental evidence and clinical observations are reviewed.ResultsA number of common downstream pathophysiologic pathways appear to be relevant in AMD manifestations irrespective of primary heterogeneous etiologies. These include sequelae of oxidative damage, retinal pigment epithelium (RPE) cell dysfunction with accumulation of lipofuscin and impairment of lysosomal functions, deposition of subsequently incompletely degraded material at the basal RPE cell side and alterations in Bruch’s membrane extracellular matrix, immunologic responses to extracellular material (drusen) with subsequent growth of drusen, induction of choroidal neovascularization as a result of imbalance between anti-angiogenetic and proangiogenetic factors as well as cell death (geographic atrophy) without prior neovascular events.ConclusionsUnderstanding is expanding regarding the sequence of events that lead to early and late lesions in AMD. Therapeutic approaches that focus on the molecular mechanisms are more likely to succeed than currently available treatment options as exemplified by the management of choroidal neovascularisations.

In Vivo Visualization of Dendritic Cells, Macrophages, and Microglial Cells Responding to Laser-Induced Damage in the Fundus of the Eye

PURPOSE To study the in vivo response of mononuclear phagocytes (i.e., dendritic cells [DCs] and macrophages [MPhis]) in the posterior eye segment after laser-induced injury, and to gain a better understanding of the role of these cells in inflammatory eye disease. METHODS CX(3)CR1(GFP/+) knockin mice were used, in which DCs, MPhis, and microglia cells (microGCs) are constitutively fluorescent. These reporter mice were examined by a confocal scanning laser ophthalmoscope (cSLO) after argon laser coagulation. cSLO was complemented by fluorescence microscopy of retinal flatmounts and eye cryosections, to study cell morphology and location, and by multicolor flow cytometry, to determine the number and identity of the fluorescent cells. RESULTS The retina of healthy reporter mice featured abundant fluorescent microGCs. After laser injury to the fundus, these cells accumulated and migrated laterally toward injury after 60 minutes. Distinctly shaped fluorescent cells accumulated within laser spots and were identified by flow cytometry and immunofluorescence microscopy as DCs and MPhis in the retina and choroid. The DCs rapidly disappeared from the retina, whereas the MPhis stayed longer. Choroidal infiltrates were detectable even 35 days after laser injury, in particular in larger spots resulting from higher laser intensity. In addition, nonfluorescent granulocytes were detected in the choroid. CONCLUSIONS The synergistic use of ophthalmoscopy, flow cytometry, and immunofluorescence microscopy allows detailed dissection of the in vivo response of mononuclear phagocytes to laser injury of the fundus. The number of microGCs increased in the retina. DCs and MPhis were present in the retina and choroid infiltrate. MPhis and granulocytes persisted in the choroid infiltrate longer than previously thought.

Fundus Autofluorescence Imaging

Ophthalmic imaging technology has revolutionized fundus examination. FAF imaging represents one of various novel tools and provides information over and above fundus photography, fluorescence angiography and optical coherence tomography. This noninvasive diagnostic tool visualizes age- and disease-related metabolic changes of the retinal pigment epithelium. The autofluorescence signal mainly derives from dominant fluorophores in lipofuscin granules of the RPE. Lipofuscin accumulation represents a common downstream pathogenetic pathway in many retinal and macular disease entities.Thus FAF imaging contributes significantly to our understanding of the pathophysiology and treatment of various retinal diseases.

[OCT in age-related macular degeneration. Findings, usage in clinical routine, and assessment of treatment outcome].

ZusammenfassungDie optische Kohärenztomographie (OCT) ist ein relativ einfach durchführbares, nichtinvasives Untersuchungsverfahren, das ein zweidimensionales Schnittbild der makulären Netzhaut ermöglicht. Obwohl diese Untersuchungsmethode bei zahlreichen Erkrankungen der Makula zum Teil schon routinemäßig Einsatz findet, ist sie bei altersabhängiger Makuladegeneration (AMD) noch kein Standardverfahren. Mit Hilfe der OCT sind sowohl quantitative als auch qualitative Aussagen bei verschiedenen Manifestationsformen der AMD möglich. Die qualitative Auswertung von OCT-Bildern umfasst unter anderem die Beurteilung des Vorhandenseins intra- oder subretinaler extrazellulärer Flüssigkeitsakkumulationen inklusive intraretinaler zystoider Hohlräume, sowie von Pigmentepithelabhebungen und retinalen angiomatösen Proliferationen (RAP). Gerade für die Beurteilung des Effekts therapeutischer Interventionen bei neovaskulärer AMD wird die OCT in der klinischen Routine weiter an Bedeutung gewinnen. Zum Therapiemonitoring neuer therapeutischer Strategien ist sie bereits fester Bestandteil klinischer Studien geworden.AbstractOptical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.Optical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.

Prognostic Impact of Renal Impairment and Sodium Imbalance in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunting for the Prevention of Variceal Rebleeding

Background/Aim: Kidney function and portal pressure have prognostic relevance in nonshunted patients with cirrhosis. Since insertion of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure and may improve the renal function, the aim of the present study was to investigate the prognostic role of renal impairment and portal hemodynamics in patients with compensated cirrhosis electively shunted due to recurrent variceal hemorrhages. Methods: Data of 101 consecutive and prospectively followed patients with compensated cirrhosis (bilirubin <5 mg/dl) undergoing elective TIPS due to recurrent variceal bleeding (45 died, and 8 were transplanted during the follow-up period) were evaluated in a multivariate Cox model. Results: Creatinine and sodium were identified as the only independent predictors of survival in this model. The 90th percentile of creatinine (>1.7 mg/dl) defined a subgroup with a similar poor prognosis as the 90th percentile of the model for end-stage liver disease (MELD) score. Neither baseline nor post-TIPS portal pressure correlated with the long-term outcome. Conclusions: In compensated patients undergoing TIPS due to variceal bleeding, renal impairment indicates a poor prognosis. Portal hemodynamic parameters are not predictive of survival in TIPS patients.

Prognostic role of the initial portal pressure gradient reduction after TIPS in patients with cirrhosis.

Background The aim of this study was to determine the prognostic relevance of the portal pressure gradient (PPG) before and after transjugular intrahepatic portosystemic stent shunt (TIPS) insertion in patients with liver cirrhosis and recurrent oesophageal variceal bleeding. Methods 118 cirrhotic patients (Child A/B/C, 41/56/21; Child score, 7.7±2.0; baseline PPG, 21.8±4.7 mmHg) underwent TIPS for the prevention of variceal rebleeding. A multivariate logistic regression analysis was applied to identify the independent determinants of rebleeding and survival. The estimated rebleeding rate and the estimated survival were compared by log–rank testing. Results TIPS insertion reduced the PPG by 53.2±17.7%. During follow-up 21 patients suffered significant rebleeding (17.8%); bleeding-related mortality was 3.4% (four patients). The median survival [95% confidence intervals (CI)] was 48.2 (39.8; 60.8) months. The multivariate Cox model identified creatinine as the only independent predictor of survival, and the initial decrease of the PPG after TIPS as the only independent predictor of rebleeding. PPG before TIPS (21.8±4.7 mmHg) and the gradient at the time of rebleeding (22.0±2.9 mmHg) did not differ significantly. Patients with an initial decrease of the PPG after TIPS <30% were at the highest risk for rebleeding. Patients with an initial decrease of the PPG >60% rarely suffered from rebleeding. Conclusions The initial decrease in the PPG after TIPS is a predictor for the risk of rebleeding but not for survival after TIPS. For that reason, in patients undergoing TIPS placement for the prevention of recurrent bleeding from oesophageal varices, an initial reduction of the PPG of 30–50% should be attempted.

OCT bei altersabhängiger Makuladegeneration

ZusammenfassungDie optische Kohärenztomographie (OCT) ist ein relativ einfach durchführbares, nichtinvasives Untersuchungsverfahren, das ein zweidimensionales Schnittbild der makulären Netzhaut ermöglicht. Obwohl diese Untersuchungsmethode bei zahlreichen Erkrankungen der Makula zum Teil schon routinemäßig Einsatz findet, ist sie bei altersabhängiger Makuladegeneration (AMD) noch kein Standardverfahren. Mit Hilfe der OCT sind sowohl quantitative als auch qualitative Aussagen bei verschiedenen Manifestationsformen der AMD möglich. Die qualitative Auswertung von OCT-Bildern umfasst unter anderem die Beurteilung des Vorhandenseins intra- oder subretinaler extrazellulärer Flüssigkeitsakkumulationen inklusive intraretinaler zystoider Hohlräume, sowie von Pigmentepithelabhebungen und retinalen angiomatösen Proliferationen (RAP). Gerade für die Beurteilung des Effekts therapeutischer Interventionen bei neovaskulärer AMD wird die OCT in der klinischen Routine weiter an Bedeutung gewinnen. Zum Therapiemonitoring neuer therapeutischer Strategien ist sie bereits fester Bestandteil klinischer Studien geworden.AbstractOptical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.Optical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.

The Impact of Lens Opacity on SD-OCT Retinal Nerve Fiber Layer and Bruch's Membrane Opening Measurements Using the Anatomical Positioning System (APS)

Purpose To evaluate the impact of lens opacity on retinal nerve fiber layer thickness (RNFLT) and Bruchs membrane opening (BMO) measurements. Methods Fifty-nine randomly selected patients without any other relevant ocular pathology undergoing elective routine cataract surgery in two specialized eye clinics were enrolled. RNFLT, BMO area, and BMO minimum rim width (BMO-MRW) were assessed with the Heidelberg Engineering Spectralis OCT using the anatomical positioning system (APS) prior to and 1 day after cataract surgery using a ring scan at different eccentricities of the disc (3.5, 4.1 and 4.7 mm). Lens opacity was quantified using densitometry based on Scheimpflug images (Oculus Pentacam AXL). Results RNFLT, BMO area, and BMO-MRW were virtually identical before and following removal of the cataractous lens. This held when assessed overall, within the six sectors for the 3.5-mm scan, or at any other eccentricity. Baseline RNFLT was not associated with lens opacity. Conclusions Using the APS, RNFLT remained unchanged following cataract surgery, contrary to results reported by previous studies. Our results imply that the APS may have contributed to more precise spectral-domain optical coherence measurements, minimizing the influence of cataract on RNFLT and BMO assessments in our cohort.

OCT bei altersabhngiger Makuladegeneration@@@OCT in age-related macular degeneration: Befunde, Einsatz in der klinischen Routine, Beurteilung des Therapieverlaufs@@@Findings, routine clinical application, and assessment of treatment effects

ZusammenfassungDie optische Kohärenztomographie (OCT) ist ein relativ einfach durchführbares, nichtinvasives Untersuchungsverfahren, das ein zweidimensionales Schnittbild der makulären Netzhaut ermöglicht. Obwohl diese Untersuchungsmethode bei zahlreichen Erkrankungen der Makula zum Teil schon routinemäßig Einsatz findet, ist sie bei altersabhängiger Makuladegeneration (AMD) noch kein Standardverfahren. Mit Hilfe der OCT sind sowohl quantitative als auch qualitative Aussagen bei verschiedenen Manifestationsformen der AMD möglich. Die qualitative Auswertung von OCT-Bildern umfasst unter anderem die Beurteilung des Vorhandenseins intra- oder subretinaler extrazellulärer Flüssigkeitsakkumulationen inklusive intraretinaler zystoider Hohlräume, sowie von Pigmentepithelabhebungen und retinalen angiomatösen Proliferationen (RAP). Gerade für die Beurteilung des Effekts therapeutischer Interventionen bei neovaskulärer AMD wird die OCT in der klinischen Routine weiter an Bedeutung gewinnen. Zum Therapiemonitoring neuer therapeutischer Strategien ist sie bereits fester Bestandteil klinischer Studien geworden.AbstractOptical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.Optical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.