Rupert H. Portugaller

Ibandronate Prevents Bone Loss and Reduces Vertebral Fracture Risk in Male Cardiac Transplant Patients: A Randomized Double-Blind, Placebo-Controlled Trial

Bone loss and fractures are common complications after cardiac transplantation (CTP). The aim of this study was to investigate whether intravenous ibandronate is an effective preventive option. Thirty‐five male cardiac transplant recipients received either ibandronate (IBN) 2 mg intravenously every 3 mo or matching placebo (CTR) in addition to 500 mg calcium carbonate and 400 IE vitamin D3. Sera were collected at CTP and every 3 mo thereafter. At baseline and 6 and 12 mo, standardized spinal X‐rays and BMD measurements were taken. Bone biopsies were taken at CTP and after 6 mo from six patients. In the IBN group, 13% of the patients sustained a new morphometric vertebral fracture compared with 53% in the CTR group (absolute risk reduction [ARR], 40%; relative risk reduction [RRR], 75%; p = 0.04). BMD remained unchanged with IBN treatment but in the CTR group decreased at the lumbar spine by 25% and at the femoral neck by 23% (both p < 0.0001) over the 1‐yr period. Serum bone resorption markers carboxy‐terminal telopeptide region of type I collagen (sCTX) and TRACP 5b were significantly increased in the CTR group and decreased in the IBN group at all time points compared with baseline. In contrast, both osteocalcin and bone‐specific alkaline phosphatase levels showed, after a similar decrease over the first 3 mo in both groups, a marked rise in the CTR subjects and steadily declining levels in the IBN patients throughout the remainder of the study period. Three paired biopsies were available from each group. Despite the small sample size, a difference in the relative change of eroded surface (68% in the CTR versus −23% in the IBN group, p < 0.05) could be shown. Intravenous IBN reduced fractures, preserved bone mass, and prevented uncoupling of bone formation and resorption after CTP. The favorable effects on bone turnover were also supported by histomorphometric findings.

Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study)

BackgroundPatients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration.Methods/DesignThe study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the study.DiscussionA volume expansion strategy showing a benefit from earlier intervention for patients with markedly elevated urinary NGAL values, indicating a CIN, might arise from data from this study.Trial registrationClinicalTrials.gov NCT01292317

The eternal tale of dialysis access vessels and restenosis: are drug-eluting balloons the solution?

In dialysis access fistulas and grafts, percutaneous transluminal angioplasty (PTA) is frequently followed by restenosis development, which results in repeated periodical re-interventions. The technique of drug-eluting balloon (DEB) angioplasty has shown promising results in the treatment of femoropopliteal arteriosclerotic lesions. In contrast to arteriosclerotic arteries, dialysis access vessels host unfavorable hemodynamics due to the direct conduction of high-pressure fluid into a low-pressure system. Hence, the beneficial effect of DEB angioplasty may be limited in this system. However, a first prospective randomized trial on 40 patients with arteriovenous fistula or graft stenoses exhibited a significantly higher 6-month primary patency of the treated lesions after DEB angioplasty than after uncoated balloon angioplasty. Despite such a positive reference, general recommendations regarding the value of DEBs in dialysis access vessels cannot be considered as serious unless large randomized controlled trials have been performed.

RFA Guardian: Comprehensive Simulation of Radiofrequency Ablation Treatment of Liver Tumors

The RFA Guardian is a comprehensive application for high-performance patient-specific simulation of radiofrequency ablation of liver tumors. We address a wide range of usage scenarios. These include pre-interventional planning, sampling of the parameter space for uncertainty estimation, treatment evaluation and, in the worst case, failure analysis. The RFA Guardian is the first of its kind that exhibits sufficient performance for simulating treatment outcomes during the intervention. We achieve this by combining a large number of high-performance image processing, biomechanical simulation and visualization techniques into a generalized technical workflow. Further, we wrap the feature set into a single, integrated application, which exploits all available resources of standard consumer hardware, including massively parallel computing on graphics processing units. This allows us to predict or reproduce treatment outcomes on a single personal computer with high computational performance and high accuracy. The resulting low demand for infrastructure enables easy and cost-efficient integration into the clinical routine. We present a number of evaluation cases from the clinical practice where users performed the whole technical workflow from patient-specific modeling to final validation and highlight the opportunities arising from our fast, accurate prediction techniques.

Intervention Planning of Hepatocellular Carcinoma Radio-Frequency Ablations

We present a software solution for planning and simulating radio-frequency ablation (RFA) treatment for patients suffering from hepatocellular carcinoma. Our software provides the graphical front-end for the results of the EU FP7 project IMPPACT. The main planning application was designed to assist with the identification of minimum-risk setups for RFA probes and generation of evaluable 3D representations of the predicted necrosis zones. Patient-specific mesh data describing the involved anatomic structures are used to individually parameterize the simulation procedure for personalized results. Our software supplies tools for extracting the required anatomic meshes from computed tomography (CT) images and for specifying custom intervention protocols. Data collected during simulations allow for detailed illustration of expected effectiveness and progress of heat-induced necrosis over time. Our software was evaluated positively by medical personnel and has been successfully put into practice at two independent European clinical sites.

Volume visualization in the clinical practice

Volumetric data is common in medicine, geology and engineering, but the O(n3) complexity in data and algorithms has prevented the widespread use of volume graphics. Recently, 3D image processing and visualization algorithms have been parallelized and ported to graphics processing units. Today, medical diagnostics highly depends on volumetric imaging methods that must be visualized in real-time. However, daily clinical practice shows that physicians still prefer simple 2D multi-planar reconstructions over 3D visualizations for intervention planning. Therefore, a very basic question in this context is, if real-time 3D image synthesis is necessary at all. This paper makes four main observations in a clinical context, which are evaluated with 24 independent physicians from three different European hospitals.

Biliary obstruction as a complication of transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt (TIPS) implantation is generally recommended before liver transplantation. Described side effects include encephalopathy with elevated ammonium levels. The development of biliary fistulas has been described as a rare but severe complication following TIPS implantation. Biliary fistulas are mainly detected upon routine ultrasonographic monitoring; clinically, they feature jaundice with elevated bilirubin. When a biliary complication occurs after TIPS implantation, the insertion of a polytetrafluoroethylene-covered stent is the management of choice and usually suffices. A 52-year-old Caucasian patient presented at our department with severe jaundice and highly elevated biliary enzymes, although the prothrombin time was within the physiological range; the liver function was within normal limits for the patient’s age. The history included documented Child’s A cirrhosis (7 points). Four months before admission, the patient had suffered an esophageal hemorrhage with subsequent implantation of a TIPS stent graft in the regular position without any record of complications. There was no documentation of peri-interventional strategies, and the patient had refused any drug therapy. Abdominal ultrasound revealed an intraportal expansion suggesting a Klatskin carcinoma. Computer tomography detected a soft mass coating the entire length of the implanted TIPS, and this suggested a concomitant biliary fistula near the artificial port. A magnetic resonance tomography study of the biliary tract showed a small fistula from a leak in the right hepatic duct that emptied into a large biloma at the hepatic porta (Fig. 1). Percutaneous cholangiography revealed that the right hepatic bile duct was compressed by the TIPS passage (Fig. 2). The biloma had displaced and compressed the hepatic bile duct bifurcation. In a redo, the TIPS was replaced with a polytetrafluoroethylene-covered Wallstent, and the biloma was drained without complications. During the peri-interventional period, the drainage worked perfectly. Despite these measures, the patient deteriorated markedly; encephalopathy developed, liver function decreased, and biliary enzymes increased. The Model for End-Stage Liver Disease score increased from 8 (4% mortality) at admission to the maximum value of 40. Various imaging studies did not show any bile retention. Within 3 weeks, the patient had developed Child’s C cirrhosis (14 points). The clinical picture of secondary sclerosing cholangitis persisted despite the standard treatment, and the patient’s liver function deteriorated rapidly. Within 3 weeks, that is, 4 weeks after admission, progressive liver failure necessitated transplantation, which was performed with the piggyback technique with retrograde reperfusion. The postoperative recovery was unremarkable. The patient is presently 54 years old, is under immunosuppression with mycophenolate mofetil and sirolimus, and has not required further hospitalization.

Is Embolization an Effective Treatment for Recurrent Hemorrhage After Hip or Knee Arthroplasty

BackgroundSpontaneous recurrent hemorrhage after arthroplasty of the hip or knee is a rare condition. In patients who do not have coagulopathy, the likeliest etiology for hemarthrosis is hypertrophic vascular synovium. Treatments include arthroscopic or open synovectomy, or angiography with embolization; however, because the condition is rare, seldom reported, and debilitating, small case series characterizing the efficacy of any approach are important to allow a collective experience with this condition to emerge.Questions/purposesWe attempted to (1) determine whether angiography with embolization can prevent recurrent hemarthrosis after hip or knee arthroplasty in a small series of patients with or without coagulopathy, and (2) evaluate complications associated with this intervention.MethodsBetween 2005 and 2014, seven patients presented with spontaneous, recurrent hemarthroses. One patient had polycythemia vera and factor XIII deficiency as underlying illnesses. All patients were treated with selective transarterial embolization, and all had followup at a minimum of 12 months (range, 12–102 months; median, 74 months). Other treatments during this time included hematoma removals and flap operations in one patient, and indications for transarterial embolization included recurrent hemarthrosis. The patients included six men and one woman with a median age of 72 years (range, 61–78 years). Five patients underwent one or more reoperations before transarterial embolization. A diagnostic workup for coagulopathy was performed in all patients; one patient was identified to have polycythemia ruba vera and factor XIII deficiency, however the patient still was treated with transarterial embolization because it was perceived to be the least invasive of available options. No other patients had a diagnosis of coagulopathy. Angiography showed hypervascularity in all patients and a contrast agent showed extravasation in two. Selective transarterial embolization of branches of the internal iliac artery, common femoral artery, deep femoral artery, or the popliteal artery was performed with polyvinyl alcohol particles, microspheres, and/or coils. Patients were followed clinically during 12 to 102 months (median, 74 months) to determine whether the hemorrhages recurred.ResultsTechnical success was achieved in all patients. No procedure-related complications were reported. On followup, recurrent hemorrhage was reported in one patient who had a diagnosis of coagulopathy before the procedure. He underwent three reinterventions and five reoperations. Three months after initial embolization, a flap procedure was performed.ConclusionsIn a small series of patients with a minimum followup of 1 year, we found selective transarterial embolization to be effective in patients without underlying coagulopathy in preventing recurrences of spontaneous recurrent hematoma or hemarthrosis of the hip and the knee. This condition is rare, therefore comparative trials are unlikely to be done. Because transarterial embolization is relatively low risk and generally well tolerated, we consider it to be a reasonable approach for consideration with other options such as arthroscopic or open synovectomy and revision arthroplasty.Level of EvidenceLevel IV, therapeutic study.

Neutrophil gelatinase-associated lipocalin (NGAL) fails as an early predictor of contrast induced nephropathy in chronic kidney disease (ANTI-CI-AKI study)

The aim of the study was to evaluate the diagnostic accuracy of urinary neutrophil gelatinase- associated lipocalin (uNGAL) in patients with chronic kidney disease (CKD) as an early biomarker for contrast induced acute kidney injury (CI-AKI) and to investigate whether patients with an uNGAL increase might benefit from an additional intravenous volume expansion with regard to CI-AKI-incidence. We performed a prospective randomized controlled trial in 617 CKD-patients undergoing intra-arterial angiography. Urinary NGAL was measured the day before and 4–6hrs after angiography. In the event of a significant rise of uNGAL patients were randomized either into Group A, who received intravenous saline post procedure or Group B, who did not receive post-procedural i.v. fluids. Ten patients (1.62%) exhibited a significant rise of uNGAL after angiography and were randomized of whom one developed a CI-AKI. In the entire cohort the incidence of CI-AKI was 9.4% (58 patients) resulting in a specificity of 98.4% (95% CI: 97.0–99.3%) and a sensitivity of 1.72% (95% CI: 0.044–9.2%) of uNGAL for the diagnosis of CI-AKI. In this study uNGAL failed to predict CI-AKI and was an inadequate triage tool to guide an early intervention strategy to prevent CI-AKI. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292317.

Successful Retrieval of an Embolized Vascular Closure Device (Angio-Seal®) After Peripheral Angioplasty

A 55-year-old male with peripheral arterial disease underwent angioplasty of the right lower limb arteries via antegrade femoral access. Angio-Seal® closure device was used to treat the puncture site, whereby the intravascular sealing anchor accidentally embolized into the malleolar region of the right posterior tibial artery. Successful retrieval of the anchor was accomplished by a SpiderFX embolic protection device. This technique may be a useful approach to retrieve embolized foreign bodies via endovascular access.