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Purpose: Information about the cost-effectiveness of a certain treatment is relevant for decision-making and healthcare providers. This study compares the cost-effectiveness of the novel Woven Endobridge (WEB) for intracranial aneurysm treatment with conventional coiling and stent-assisted coiling (SAC) from the perspective of the German Statutory Health Insurance., Methods: A patient-level simulation was constructed to simulate 55-year-old patients with an unruptured middle cerebral artery aneurysm (size: 3-11 mm) considering WEB treatment, coiling or SAC in terms of morbidity, angiographic outcome, retreatment, procedural and rehabilitation costs and rupture rates. Incremental cost-effectiveness ratios (ICERs) were calculated as costs per quality-adjusted life years (QALYs) and costs per year with neurologic morbidity avoided. Uncertainty was explored with deterministic and probabilistic sensitivity analyses. The majority of data were obtained from prospective multi-center studies and meta-analyses of non-randomized studies., Results: In the base case, lifetime QALYs were 13.24 for the WEB, 12.92 for SAC and 12.68 for coiling. Lifetime costs were 20,440 € for the WEB, 23,167 € for SAC, and 8200 € for coiling. Compared to coiling, the ICER for the WEB was 21,826 €/QALY, while SAC was absolutely dominated by WEB. Probabilistic sensitivity analysis revealed that at a willingness-to-pay of ≥ 30,000 €/QALY, WEB was the preferred treatment. Deterministic sampling showed that the discount rate, material costs and retreatment rates had the largest impact on the ICERs., Conclusion: The novel WEB showed at least comparable cost-effectiveness to SAC for treatment of broad-based unruptured aneurysms. Considering all three modalities, coiling had the least costs; however this modality is often not appropriate for the treatment of wide-necked aneurysms., (© 2023. The Author(s).)

Background: For patients with acute myocardial infarction (AMI), direct coronary angiography (CA) is recommended, while for non-AMI patients, the diagnostic work-up depends on clinical criteria. This analysis provides initial prospective German data for the degree of guideline-adherence (GL) in the use of CA on non-AMI patients presenting at the emergency department (ED) with suspected acute coronary syndrome (ACS) according to the 2015 ESC-ACS-GL. Furthermore the implications of the application of the 2020 ESC-ACS-GL recommendations were evaluated., Methods: Patient symptoms were identified using a standardized questionnaire; medical history and diagnostic work-up were acquired from health records. In accordance with the 2015 ESC-ACS-GL, CA was considered GL-adherent if intermediate risk criteria (IRC) were present or non-invasive, image-guided testing (NIGT) was pathological., Results: Between January 2019 and August 2021, 229 patients were recruited across seven centers. Patients presented with chest pain, dyspnea, and other symptoms in 66.7%, 16.2% and 17.1%, respectively, were in mean 66.3 ± 10.5 years old, and 36.3% were female. In accordance with the 2015 ESC-ACS-GL, the use of CA was GL-adherent for 64.0% of the patients. GL-adherent compared to non-adherent use of CA resulted in revascularization more often (44.5% vs. 17.1%, p < 0.001). Applying the 2020 ESC-ACS-GL, 20.4% of CA would remain GL-adherent., Conclusions: In the majority of cases, the use of CA was adherent to the 2015 ESC-ACS-GL. With regard to the 2020 and 2023 ESC-ACS-GL, efforts to expand the utilization of NIGT are crucial, especially as GL-adherent use of CA is more likely to result in revascularization.(German Clinical Trials Register DRKS00015638; https://drks.de/search/de/trial/DRKS00015638; (registration date: 19 February 2019))., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: With 900'000 coronary angiographies (CA) per year, Germany has the highest annual per capita volume in Europe. Until now there are no prospective clinical data on the degree of guideline-adherence in the use of CA in patients with suspected chronic coronary syndrome (CCS) in Germany., Methods: Between January 2019 and August 2021, 458 patients with suspected CCS were recruited in nine German centres. Guideline-adherence was evaluated according to the current European Society of Cardiology and German guidelines. Pre-test probability (PTP) for CAD was determined using age, gender, and a standardized patient questionnaire to identify symptoms. Data on the diagnostic work-up were obtained from health records., Results: Patients were in mean 66.6 years old, male in 57.3 %, had known CAD in 48.4 % and presented with typical, atypical, non-anginal chest pain or dyspnoea in 35.7 %, 41.3 %, 23.0 % and 25.4 %, respectively. PTP according to the European guidelines was in mean 24.2 % (11.9 %-36.5 % 95 % CI). 20.9 % of the patients received guideline-recommended preceding non-invasive image guided testing. The use of CA was adherent to the European and German guideline recommendations in 20.4 % and 25.4 %, respectively. In multivariate-analysis, arterial hypertension and prior revascularization were predictors of guideline non-adherence., Conclusion: These are the first prospective clinical data which demonstrated an overall low degree of guideline-adherence in the use of CA in patients with suspected CCS in the German health care setting. To improve adherence rates, the availability of and access to non-invasive image guided testing needs to be strengthened. (German Clinical Trials Registry DRKS00015638 - Registration Date: 19.02.2019)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Infantile nephropathic cystinosis, due to impaired transport of cystine out of lysosomes, occurs with an incidence of 1 in 100-200,000 live births. It is characterized by renal Fanconi syndrome in the first year of life and glomerular dysfunction progression to end-stage kidney disease by approximately 10 years of age. Treatment with oral cysteamine therapy helps preserve glomerular function, but affected individuals eventually require kidney replacement therapy. This is because glomerular damage had already occurred by the time a child is diagnosed with cystinosis, typically in the second year of life. We performed a retrospective multicenter study to investigate the impact of initiating cysteamine treatment within the first 2 months of life in some infants and comparing two different levels of adherence in patients diagnosed at the typical age. We collected 3983 data points from 55 patients born between 1997 and 2020; 52 patients with 1592 data points could be further evaluated. These data were first analyzed by dividing the patient cohort into three groups: (i) standard treatment start with good adherence, (ii) standard treatment start with less good adherence, and (iii) early treatment start. At every age, mean estimated glomerular filtration rate (eGFR) was higher in early-treated patients than in later-treated patients. Second, a generalized additive mixed model (GAMM) was applied showing that patients with initiation of treatment before 2 months of age are expected to have a 34 ml/min/1.73 m 2 higher eGFR than patients with later treatment start while controlling for adherence and patients' age. These data strongly suggest that oral cysteamine treatment initiated within 2 months of birth preserves kidney function in infantile nephropathic cystinosis and provide evidence of the utility of newborn screening for this disease., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Fibroblast activation protein (FAP) is a promising target for diagnosis and therapy of numerous malignant tumors. FAP-2286 is the conjugate of a FAP-binding peptide, which can be labeled with radionuclides for theranostic applications. We present the first-in-humans results using 177 Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177 Lu-FAP-2286 was performed on 11 patients with advanced adenocarcinomas of the pancreas, breast, rectum, or ovary after prior confirmation of uptake on 68 Ga-FAP-2286 or 68 Ga-FAPI-04 PET/CT. Results: Administration of 177 Lu-FAP-2286 (5.8 ± 2.0 GBq; range, 2.4-9.9 GBq) was well tolerated, with no adverse symptoms or clinically detectable pharmacologic effects being noticed or reported in any of the patients. The whole-body effective dose was 0.07 ± 0.02 Gy/GBq (range, 0.04-0.1 Gy/GBq). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range, 0.4-2.0 Gy/GBq) and 0.05 ± 0.02 Gy/GBq (range, 0.03-0.09 Gy/GBq), respectively. Significant uptake and long tumor retention of 177 Lu-FAP-2286 resulted in high absorbed tumor doses, such as 3.0 ± 2.7 Gy/GBq (range, 0.5-10.6 Gy/GBq) in bone metastases. No grade 4 adverse events were observed. Grade 3 events occurred in 3 patients-1 with pancytopenia, 1 with leukocytopenia, and 1 with pain flare-up; 3 patients reported a pain response. Conclusion: 177 Lu-FAP-2286 PTRT, applied in a broad spectrum of cancers, was relatively well tolerated, with acceptable side effects, and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Peptide receptor radionuclide therapy (PRRT) of patients with somatostatin receptor expressing neuroendocrine neoplasms has shown promising results in clinical trials and a recently published phase III study., Methods: In our center, 2294 patients were screened between 2004 and 2014 by 68 Ga somatostatin receptor (SSTR) PET/CT. Intention to treat analysis included 1048 patients, who received at least one cycle of 90 Yttrium or 177 Lutetium-based PRRT. Progression free survival was determined by 68 Ga SSTR-PET/CT and EORTC response criteria. Adverse events were determined by CTCAE criteria., Results: Overall survival (95% confidence interval) of all patients was 51 months (47.0-54.9) and differed significantly according to radionuclide, grading, previous therapies, primary site and functionality. Progression free survival (based on PET/CT) of all patients was 19 months (16.9-21), which was significantly influenced by radionuclide, grading, and origin of neuroendocrine neoplasm. Progression free survival after initial progression and first and second resumption of PRRT after therapy-free intervals of more than 6 months were 11 months (9.4-12.5) and 8 months (6.4-9.5), respectively. Myelodysplastic syndrome or leukemia developed in 22 patients (2.1%) and 5 patients required hemodialysis after treatment, other adverse events were rare., Conclusion: PRRT is effective and overall survival is favorable in patients with neuroendocrine neoplasms depending on the radionuclide used for therapy, grading and origin of the neuroendocrine neoplasm which is not exactly mirrored in progression free survival as determined by highly sensitive 68 Ga somatostatin receptor PET/CT using EORTC criteria for determining response to therapy., Competing Interests: CONFLICTS OF INTEREST R.P. Baum received honoraria from Ipsen Pharma, ROTOP Pharmaka, OctreoPharm Sciences GmbH and Advanced Accelerator Applications outside the submitted work; H.R. Kulkarni has nothing to disclose; K. Niepsch has nothing to disclose; D. Kaemmerer received travel support by the companies IPSEN Pharma GmbH and Pfizer; D. Mueller is inventor of the herein mentioned NaCl based 68Ga labeling method. In some countries, patent applications have been registered; V. Prasad has nothing to disclose; M. Hommann has nothing to disclose; F. Robiller has nothing to disclose; A. Singh has nothing to disclose; H. Franz reports personal fees from Zentralklinik Bad Berka, during the conduct of the study; A. Jochems has nothing to disclose; P. Lambin is member is the Scientific advisory board of the companies DNAmito and Oncoradiomics and is inventor of several radiomics patents; D. Hörsch reports personal fees from Lexicon Pharma Inc, grants and personal fees from Ipsen Pharma Inc, during the conduct of the study; grants and personal fees from Novartis Pharma Inc, personal fees from Pfizer Pharma Inc, grants and personal fees from Ipsen Pharma Inc, personal fees from Lexicon Pharma Inc, outside the submitted work.

Background: The aim of this study was to assess the potential for radiation dose reduction using knowledge-based iterative model reconstruction (K-IMR) algorithms in combination with ultra-low dose body mass index (BMI)-adapted protocols in coronary CT angiography (coronary CTA)., Methods: Forty patients undergoing clinically indicated coronary CTA were randomly assigned to two groups with BMI-adapted (I: <25.0 kg/m 2 , II: <28.0 kg/m 2 , III: <30.0 kg/m 2 , IV: ≥30.0 kg/m 2 ) low dose (LD, I: 100kV p /75 mAs, II: 100kV p /100 mAs, III: 100kV p /150 mAs, IV: 120kV p /150 mAs, n = 20) or ultra-low dose (ULD, I: 100kV p /50 mAs, II: 100kV p /75 mAs, III: 100kV p /100 mAs, IV: 120kV p /100 mAs, n = 20) protocols. Prospectively-triggered coronary CTA was performed using a 256-MDCT with the lowest reasonable scan length. Images were generated with filtered back projection (FBP), a noise-reducing hybrid iterative algorithm (iD, levels 2/5) and K-IMR using cardiac routine (CR) and cardiac sharp settings, levels 1-3., Results: Groups were comparable regarding anthropometric parameters, heart rate, and scan length. The use of ULD protocols resulted in a significant reduction of radiation exposure (0.7 (0.6-0.9) mSv vs. 1.1 (0.9-1.7) mSv; p < 0.02). Image quality was significantly better in the ULD group using K-IMR CR 1 compared to FBP, iD 2 and iD 5 in the LD group, resulting in fewer non-diagnostic coronary segments (2.4% vs. 11.6%, 9.2% and 6.1%; p < 0.05)., Conclusions: The combination of K-IMR with BMI-adapted ULD protocols results in significant radiation dose savings while simultaneously improving image quality compared to LD protocols with FBP or hybrid iterative algorithms. Therefore, K-IMR allows for coronary CTA examinations with high diagnostic value and very low radiation exposure in clinical routine., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

For successful labeling, (68)Ge/(68)Ga generator eluate has to be concentrated (from 10 mL or more to less than 1 mL) and to be purified of metallic impurities, especially Fe(III), and (68)Ge breakthrough. Anionic, cationic and fractional elution methods are well known. We describe two new methods: (1) a combined cationic-anionic purification and (2) an easy-to-use and reliable cationic purification with NaCl solution. Using the first method, (68)Ga from 10 mL generator eluate was collected on a SCX cartridge, then eluted with 1.0 mL 5.5 M HCl directly on an anion exchanger (30 mg AG1X8). After drying with a stream of helium, (68)Ga was eluted with 0.4 mL water into the reaction vial. We provide as an example labeling of BPAMD. Using the second method, (68)Ga from 10 mL generator eluate was collected on a SCX cartridge, then eluted with a hydrochloric solution of sodium chloride (0.5 mL 5 M NaCl, 12.5 μL 5.5 M HCl) into the reaction vial, containing 40 μg DOTATOC and 0.5 mL 1 M ammonium acetate buffer pH 4.5. After heating for 7 min at 90°C, the reaction was finished. Radiochemical purity was higher than 95% without further purification. No (68)Ge breakthrough was found in the final product.