Jennifer Nadal

Implementation of the KDIGO guideline on lipid management requires a substantial increase in statin prescription rates

The KDIGO guideline on lipid management in adult patients with chronic kidney disease (CKD) reflects a paradigm shift as proposals for statin use are based on cardiovascular risk rather than cholesterol levels. Statin use is now universally recommended in CKD patients 50 years and older, assuming a 10-year risk of coronary heart disease (CHD) of over 10%. Specific comorbidities or formal risk calculation are required for younger patients. It is unknown to which extent these new guidelines differ from previous practice. Here we analyzed statin use in the German Chronic Kidney Disease study of 5217 adult patients with moderately severe CKD under nephrological care enrolled shortly before publication of the new guideline. Accordingly, 407 patients younger than 50 years would be eligible for statins compared with the 277 patients treated so far, and all 4224 patients 50 years and older would be eligible compared with the 2196 already treated. Overall, guideline implementation would almost double statin prescription from 47 to 88%. Among patients 50 years and older currently not on a statin, an estimated 10-year CHD and atherosclerotic event risks over 10% were present in 68% and 82%, respectively. Thus, implementation of the new lipid guideline requires a substantial change in prescription practice, even in CKD patients under nephrological care. Based on comorbidities and risk estimates, the universal recommendation for statin use in CKD patients 50 years and older appears justified.

Prospective Evaluation of Passive Expansion of Partially Dilated Transjugular Intrahepatic Portosystemic Shunt Stent Grafts-A Three-Dimensional Sonography Study.

PURPOSE To prospectively investigate early expansion kinetics of underdilated self-expanding stent grafts used for transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS Twenty patients (7 female; mean age 66 y; range, 31-80 y) with liver cirrhosis undergoing TIPS creation for variceal bleeding (n = 5), refractory ascites (n = 14), or both (n = 1) with underdilation of 10-mm stent grafts received two-dimensional (2-D) and three-dimensional (3-D) ultrasound (US) examinations immediately after TIPS creation and 1 and 6 weeks later. Orthogonal views of the TIPS within the parenchymal tract were reconstructed from 3-D volume data sets acquired in longitudinal orientation of the stent. 2-D images and reconstructed 3-D images were used for blinded diameter measurements. Measurement technique was validated with intrainterventional plain radiographs with a sizing catheter as the gold standard. Diameter changes over time and interrelations with patient characteristics (null hypothesis: no expansion, no interrelation) were analyzed using a general linear model for repeated measures. RESULTS After dilation to 8-mm diameter, 2-D and 3-D measurements showed stent recoil (mean diameter 7.7 mm ± 0.21 and 7.6 mm ± 0.17, respectively). Diameter increased significantly from initial measurements to measurements at 1 and 6 weeks (2-D, 8.8 mm ± 0.24 and 9.4 mm ± 0.15, both P < .001; 3-D, 8.7 mm ± 0.27 and 9.4 mm ± 0.11, both P < .001). Validation measurements showed no significant differences between 2-D or 3-D US and gold standard. There were no statistically significant associations between stent expansion and clinical parameters (sex, P = .78; age, P = .82; etiology/grade of cirrhosis, P = .99; indication for TIPS, P = .78, liver stiffness, P = .70). CONCLUSIONS Underdilated self-expanding stent grafts used for TIPS creation significantly expand within first 6 weeks after intervention. These changes can be noninvasively monitored using 3-D US.

Prevalence, Natural Course, and Prognostic Role of Refractile Drusen in Age-Related Macular Degeneration

Purpose To report prevalence, clinical characteristics, and prognostic significance of refractile drusen in eyes with intermediate age-related macular degeneration (AMD). Methods Presence of refractile drusen by color fundus photography (CFP), corresponding findings by multimodal imaging, and longitudinal changes with annual examinations for up to 4 years were analyzed within a prospective natural history study of 98 eyes with non-late AMD of 98 patients (Age-Related Eye Disease Study [AREDS] stages 3 and 4). Results A total of 115 refractile drusen were detected at baseline in 20 eyes (20.4%). Refractile drusen typically showed hyperreflectivity by infrared (80.9%) and blue (93.9%) reflectance imaging, appearing more distinct when compared to CFP. Laminar intense hyperreflectivity of Bruchs membrane was detected in 31 lesions by spectral-domain optical coherence tomography and was strongly related to atrophy development (23 out of 31 lesions). Presence of refractile drusen at baseline was overall associated with later development of geographic atrophy (GA) (9/20 eyes versus 6/78 eyes, P < 0.001). Spontaneous regression without evident atrophy occurred in seven lesions. Conclusions Refractile drusen are a relative common phenotype in intermediate AMD and appear to confer risk for the development of late AMD. While not all lesions develop late AMD and regression may also occur, distinct subphenotypes as identified by multimodal imaging may not only be visible earlier but also be topographically associated with the risk for GA development. Recognizing the characteristic pattern on multimodal imaging would inform physicians for identification of the lesion and its clinical history.

Yttrium-90 Radioembolization of Advanced, Unresectable Breast Cancer Liver Metastases—A Single-Center Experience

PURPOSE To determine value of transarterial radioembolization (TARE) for palliative treatment of unresectable liver-dominant breast metastases (LdBM) and to determine prognostic parameters. MATERIALS AND METHODS Records of patients undergoing TARE for progressing LdBM between June 2006 and March 2015 were retrospectively reviewed; 44 female patients (mean age 56.1 y; range, 34.9-85.3 y) underwent 69 TAREs (56 resin-based, 13 glass-based). Of 44 patients, 42 had bilobar disease. Mean administered activity was 1.35 GBq ± 0.71. Median clinical and imaging follow-up times were 121 days (range, 26-870 d; n = 42 patients) and 93 days (range, 26-2,037 d; n = 38 patients). Clinical and biochemical toxicities, imaging response (according to Response Evaluation Criteria In Solid Tumors), time to progression, and overall survival (OS) were evaluated. Data were analyzed with stratification according to clinical and procedural parameters. RESULTS Toxicities included 1 cholecystitis (grade 2) and 1 duodenal ulceration (grade 3); no grade ≥ 4 clinical toxicities were noted. Objective response rate (complete + partial response) was 28.9% (11/38); disease control rate (response + stable disease) was 71.1% (27/38). Median time to progression of treated liver lobe was 101 days (range, 30-2,037 d). During follow-up, 34/42 patients died (median OS after first TARE: 184 d [range 29-2,331 d]). On multivariate analysis, baseline Eastern Cooperative Oncology Group (ECOG) status of 0 (P < .0001, hazard ratio [HR] = 0.146) and low baseline γ-glutamyltransferase (GGT) levels (P = .0146, HR = 0.999) were predictors of longer OS. CONCLUSIONS TARE can successfully delay progression of therapy-refractory LdBM with low complication rate. Nonelevated baseline ECOG status and low GGT levels were identified as prognostic factors.

Progression of Late-Onset Stargardt Disease.

Purpose Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. Methods We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset ≥ 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. Results Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. Conclusions We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.

Percutaneous CT-Guided Radiofrequency Ablation of Solitary Small Renal Masses: A Single Center Experience.

PURPOSE To analyze the outcome of patients undergoing percutaneous CT-guided radiofrequency ablation (RFA) of small renal masses (SRM) at a single center during a ten-year time period. MATERIALS AND METHODS Patient records of renal RFAs (07/2003 - 11/2013) were reviewed. Indications were SRM suspicious of malignancy on imaging and one of the following: severe comorbidity; old age; solitary kidney; impaired renal function; patient wish. Biopsy was performed at the time of RFA. Patients were excluded if no follow-up was available. Patient and procedural characteristics were recorded. Survival rates were calculated using the Kaplan-Meiers method and compared with log-rank or cox tests. RESULTS 38 patients (16 females, mean age 70.0 years [range 52 - 87]) presenting with a solitary SRM were included in the study. Biopsy showed malignancy in 29 patients; 9 had benign tumors. 26 patients suffered from cardiovascular, respiratory or hepatic comorbidities. Technical success (complete ablation on first follow-up) was achieved in 95 % of cases. Two major complications (bowel perforation; hematothorax) occurred. The 3- and 7-year overall survival (OS) [any cause] rates were 73.4 ± 0.8 % and 50.3 ± 1.0 %, respectively (mean follow-up 54.6 months, range 1 - 127). 4 recurrences and 2 metastases were observed. The presence of comorbidities was the only independent predictor of OS. There was no difference in survival between patients with benign and malignant tumors. CONCLUSION RFA of SRM is successful in a large percentage of cases with a low complication rate and durable local control. As RFA is typically performed in multimorbid patients, overall survival seems to depend primarily on comorbidities rather than cancer progression. Key Points • RFA of SRM is technically successful in the majority of cases. • RFA leads to a high degree of local tumor control. • Post-RFA most patients ultimately die of comorbidities. • Overall survival post-RFA does not significantly differ between benign and malignant tumors in multimorbid patients.

Efficacy and time-to-hemostasis of antegrade femoral access closure using the ExoSeal vascular closure device: a retrospective single-center study.

OBJECTIVE To retrospectively evaluate the efficacy and time-to-hemostasis of antegrade femoral access closure using the ExoSeal vascular closure device (VCD). DESIGN Retrospective, single-center analysis. MATERIALS AND METHODS Between September 2010 and February 2013, 148 ExoSeal VCD closures (5-7F) of antegrade femoral accesses were performed in 119 patients (70 males, mean age 71.6 years, range 40-97 years). In all cases initial diagnostic angiography was performed via an 18G/3.8F retrograde femoral access, which was left in place during intervention (in-house standard) and was used to obtain control angiography after successful closure of the antegrade access to determine hemostasis. Technical device success was defined as ExoSeal closure without major VCD-related complications; procedural success as hemostasis within 5 minutes. Statistical analysis was performed using a logistic regression model and correlation analyses. RESULTS 145/148 (98.0%) ExoSeal closures were technically successful (5F: n = 76; 6F: n = 65; 7F: n = 7). Angiographic control showed closure after 2 minutes in 130/145 cases. In a further 14 cases hemostasis was achieved after an additional 3 minutes MC, so that closure was successful within 5 minutes in 144/148 cases (97.3%). No major complication occurred. One minor complication was recorded in a 6F access case. Pre-interventional activated partial thromboplastin time (aPTT) was the only statistically significant predictor of necessary manual compression (MC) > 2 minutes (p = .01), but with an odds-ratio of only 1.038. The INR showed an odds-ratio of 2.455 for need for 5 minutes MC (NS). Significant correlations were found between the need for 5 minutes MC and medication with acetylsalicylic acid (p = .01), clopidogrel (p < .01), and abciximab (p < .001). CONCLUSION ExoSeal vascular closure of antegrade femoral punctures is safe and effective with a low complication rate. Two minutes of MC are sufficient to achieve hemostasis in the majority of cases. However, in patients on antiplatelet therapy, especially after abciximab, the authors advocate prolonging MC to 5 minutes.

Daytime Systolic Ambulatory Blood Pressure With a Two-Step Switch From Candesartan to Olmesartan Monotherapy and the Fixed-Dose Combination of Olmesartan/Amlodipine in Patients With Uncontrolled Essential Hypertension (SEVICONTROL-2)

The objective of this study was to investigate the efficacy of the fixed‐dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single‐arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug‐related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.

Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease

Purpose To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Methods Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbulls estimator. Results A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). Conclusions These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

Value and risk of laparoscopic surgery in hemophiliacs—experiences from a tertiary referral center for hemorrhagic diatheses

PurposeLaparoscopic surgery (LS) is gaining popularity worldwide because of benefits like faster recovery, earlier hospital discharge, and better cosmetic results. In hemophiliacs, surgery in general harbors an increased risk for severe complications. Whether LS or conventional surgery (CS) should be recommended in these patients is controversial and therefore the issue of our present study.MethodsWe performed a retrospective matched-pair analysis including laparoscopically operated non-hemophiliacs (LONH), laparoscopically operated hemophiliacs (LOH), and conventionally operated hemophiliacs (COH) concerning duration of surgery, drainages, hospital stay, complications, factor use (VIII, IX, and X), and blood values. Mann-Whitney U test was used (significance level P = 0.05).ResultsNo significant differences were found in duration of surgery and drains in laparoscopically or conventionally operated hemophiliacs versus matched pairs. Complication rate did not differ among the different groups.Concerning the total duration of hospital stay (t-DHOS) and the postoperative duration of hospital stay (p-DHOS), there was no statistical difference between LOH versus matched LONH. However, in COH versus matched LOH, a longer time was required for preparation and recovery (t-DHOS, P = 0.04; p-DHOS, P < 0.001).Also, the median factor supply perioperatively including the day of surgery did not differ between laparoscopically versus conventionally operated hemophiliacs.ConclusionsOur study underscores the safety and benefits of laparoscopic procedures in hemophiliacs by showing a significantly shorter hospital stay for these patients resulting in reduced therapeutic costs and a faster mobilization. Still, the surgical and perioperative management of hemophiliacs continues to be a challenge requiring an experienced interdisciplinary team.