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Background Aneurysms of the pulmonary arteries and the ascending aorta are rare, and both bear a high mortality risk if left untreated. In general, these entities are primarily caused by etiologies such as hypertension, pulmonary arterial hypertension, infection or congenital disorders. Treatment requires a rapid diagnostic work-up or even immediate surgical intervention in acute cases. Nevertheless, surgery entails serious perioperative risks, in particular in patients with multiple comorbidities. Case presentation We discuss a 70-year-old woman presented with decompensated heart failure based on severe pulmonary artery hypertension, coincided by a massive pulmonary artery aneurysm with secondary embolism. Additional diagnostic imaging also showed a chronic post-dissection, saccular aneurysm of the ascending aorta. To our knowledge, this simultaneous diagnosis of a saccular aneurysm of the ascending aorta and a large aneurysm of the pulmonary artery with secondary embolism has not yet been described. Nonetheless, conservative treatment was chosen due to extensive pulmonal and cardiovascular comorbidities and the high-risk profile of surgery. Conclusions Extensive aneurysmatic disease of the pulmonary arteries and ascending aorta come with a serious burden of disease, especially if coincided by severe pulmonal and cardiovascular comorbidities. Both conditions can be curatively treated by surgical intervention. However, in every case the risk of surgery and the patient’s vitality, comorbidities and wishes should be taken into account to formulate an adequate treatment plan. Therefore, shared decision making is of utter importance.

Several disease related factors of pulmonary hypertension (PH) can negatively impact the nutritional status, leading to an increased risk of malnutrition. However, there are no studies on the best method for nutritional screening in PH patients. Therefore, the aim of this study was to determine the diagnostic accuracy of two screening tools: the Malnutrition Universal Screening Tool (MUST) and the Mini Nutritional Assessment Short‐Form (MNA‐SF). This cross‐sectional single center study included PH outpatients. Cut‐off values MUST ≥ 1 and MNA‐SF ≤ 11 were used for state of (risk of) malnutrition. The diagnostic criteria of the Global Leadership Initiative on Malnutrition (GLIM) were used as reference for diagnosing malnutrition. Diagnostic accuracy was determined by sensitivity, specificity, predictive positive value, negative predictive value, Cohen's Kappa‐ value (K) and area under the curve. Out of the 103 PH patients (age 67 years (SD 11.5), 66% female), 27% were malnourished according to the GLIM criteria. Both MUST and MNA‐SF had an insufficient sensitivity (60.7% [CI: 41%–97%] vs. 64.3% [CI: 44%–81%]). The MUST had a specificity of 100% [CI: 95%–100%], PPV 100% [CI:94%–100%] and NPV 87.2% [CI:79%–93%]. The specificity of the MNA‐SF was 81.3% [CI:70%–89%], PPV 56.3% [CI: 39%–73%] and NPV 85.9% [CI: 77%–93%]. The MUST had a higher K‐value 0.692 and AUC (0.804) compared to the K‐value 0.437 and AUC (0.728) of the MNA‐SF. This study indicated that both MUST and MNA‐SF are inaccurate to detect (risk of) malnutrition in PH outpatients. Future studies are needed to strive for a more sensitive screening tool.

In patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), pretreatment with PH‐targeted medical therapy may be beneficial to improve clinical parameters and pulmonary hemodynamics. This study aims to describe clinical results of PH‐targeted therapy prior to BPA. All consecutive patients with CTEPH who underwent BPA treatment were selected from our CTEPH database. Medical treatment strategy, clinical parameters, and pulmonary hemodynamics at time of diagnosis and at the first BPA were analyzed. In total 92 CTEPH patients who started BPA treatment (64.1% women; 60.4 ± 14.1 years of age; 62.0% NYHA FC III/IV) were included. Most patients received dual oral PH‐targeted medical therapy (68.5%) prior to BPA. Between diagnosis and first BPA (median time 13.9 [7.5–30.7] months) significant improvements were observed in patients treated with PH‐targeted medical therapy for both clinical (6MWD: +28.2 m [5.1–51.3], log NTproBNP: −0.4 pg/ml [−0.8 to −0.1]) as well as pulmonary hemodynamic parameters (mPAP: −6.5 mmHg [−8.5 to −4.5], CO: +0.6 L/min [0.2–1.0] and PVR: −2.8 WU [−3.5 to −2.1]). The overall complication rate per BPA (out of a total of 441 procedures) was 15.0% for patients on monotherapy and 14.9% for those on dual/triple PH‐targeted medical therapy. No severe complications occurred. In conclusion, pretreatment with PH‐targeted medical therapy prior to BPA results in an improvement in clinical‐ and pulmonary hemodynamic parameters.

Advertisers are increasingly monitoring people's online behavior and using the information collected to show people individually targeted advertisements. This phenomenon is called online behavioral advertising (OBA). Although advertisers can benefit from OBA, the practice also raises concerns about privacy. Therefore, OBA has received much attention from advertisers, consumers, policymakers, and scholars. Despite this attention, there is neither a strong definition of OBA nor a clear accumulation of empirical findings. This article defines OBA and provides an overview of the empirical findings by developing a framework that identifies and integrates all factors that can explain consumer responses toward OBA. The framework suggests that the outcomes of OBA are dependent on advertiser-controlled factors (e.g., the level of personalization) and consumer-controlled factors (e.g., knowledge and perceptions about OBA and individual characteristics). The article also overviews the theoretical positioning of OBA by placing the theories that are used to explain consumers' responses to OBA in our framework. Finally, we develop a research agenda and discuss implications for policymakers and advertisers.

Treatment options for recurrent glioblastoma are scarce, with second-line chemotherapy showing only modest activity against the tumour. Despite the absence of well controlled trials, bevacizumab is widely used in the treatment of recurrent glioblastoma. Nonetheless, whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear. We report the results of the first randomised controlled phase 2 trial of bevacizumab in recurrent glioblastoma. The BELOB trial was an open-label, three-group, multicentre phase 2 study undertaken in 14 hospitals in the Netherlands. Adult patients (≥18 years of age) with a first recurrence of a glioblastoma after temozolomide chemoradiotherapy were randomly allocated by a web-based program to treatment with oral lomustine 110 mg/m2 once every 6 weeks, intravenous bevacizumab 10 mg/kg once every 2 weeks, or combination treatment with lomustine 110 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Randomisation of patients was stratified with a minimisation procedure, in which the stratification factors were centre, Eastern Cooperative Oncology Group performance status, and age. The primary outcome was overall survival at 9 months, analysed by intention to treat. A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination treatment group. This trial is registered with the Nederlands Trial Register (www.trialregister.nl, number NTR1929). Between Dec 11, 2009, and Nov 10, 2011, 153 patients were enrolled. The preplanned safety analysis was done after eight patients had been treated, because of haematological adverse events (three patients had grade 3 thrombocytopenia and two had grade 4 thrombocytopenia) which reduced bevacizumab dose intensity; the lomustine dose in the combination treatment group was thereafter reduced to 90 mg/m2. Thus, in addition to the eight patients who were randomly assigned to receive bevacizumab plus lomustine 110 mg/m2, 51 patients were assigned to receive bevacizumab alone, 47 to receive lomustine alone, and 47 to receive bevacizumab plus lomustine 90 mg/m2. Of these patients, 50 in the bevacizumab alone group, 46 in the lomustine alone group, and 44 in the bevacizumab and lomustine 90 mg/m2 group were eligible for analyses. 9-month overall survival was 43% (95% CI 29–57) in the lomustine group, 38% (25–51) in the bevacizumab group, 59% (43–72) in the bevacizumab and lomustine 90 mg/m2 group, 87% (39–98) in the bevacizumab and lomustine 110 mg/m2 group, and 63% (49–75) for the combined bevacizumab and lomustine groups. After the reduction in lomustine dose in the combination group, the combined treatment was well tolerated. The most frequent grade 3 or worse toxicities were hypertension (13 [26%] of 50 patients in the bevacizumab group, three [7%] of 46 in the lomustine group, and 11 [25%] of 44 in the bevacizumab and lomustine 90 mg/m2 group), fatigue (two [4%], four [9%], and eight [18%]), and infections (three [6%], two [4%], and five [11%]). At the time of this analysis, 144/148 (97%) of patients had died and three (2%) were still on treatment. The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies. However, the results in the bevacizumab alone group do not justify further studies of this treatment. Roche Nederland and KWF Kankerbestrijding.

Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidneys and reabsorbed and partially retained in the proximal tubules, causing dose-limiting nephrotoxicity. An overview of renal handling of radiolabeled peptides and resulting nephrotoxicity is presented, and strategies to reduce nephrotoxicity are discussed. Modification of size, charge, or structure of radiolabeled peptides can alter glomerular filtration and tubular reabsorption. Coinfusion of competitive inhibitors of reabsorption also interferes with the interaction of peptides with renal endocytic receptors; coinfusion of basic amino acids is currently used for kidney protection in clinical PRRT. Furthermore, nephrotoxicity may be reduced by dose fractionation, use of radioprotectors, or use of mitigating agents. Decreasing the risk of nephrotoxicity allows for administration of higher radiation doses, increasing the effectiveness of PRRT.

This study is a simple illustration of the benefit of averaging over cohorts, rather than developing a prediction model from a single cohort. We show that models trained on data from multiple cohorts can perform significantly better in new settings than models based on the same amount of training data but from just a single cohort. Although this concept seems simple and obvious, no current prediction model development guidelines recommend such an approach.

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [ 111 In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging. Primary study outcomes are safety and feasibility of this multimodal imaging approach. Secondary outcomes are determination of the optimal dose, correlation between tracer uptake and histopathology and effects on clinical strategy. Administration of [ 111 In]In-DOTA-labetuzumab-IRDye800CW is well-tolerated and enables sensitive pre- and intraoperative imaging in patients who receive 10 or 50 mg of the tracer. Preoperative imaging revealed previously undetected lymph node metastases in one patient, and intraoperative fluorescence imaging revealed four previously undetected metastases in two patients. Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures. Imaging of tumor burden during surgery can lead to better tumor resection. Here, the authors develop a fluorescent probe that binds to carcinoembryonic antigen, expressed on colorectal cancer cells, and describe the results of their phase I clinical trial.

The success of cellular therapies will depend in part on accurate delivery of cells to target organs. In dendritic cell therapy, in particular, delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. We show here that in vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information. Autologous dendritic cells were labeled with a clinical superparamagnetic iron oxide formulation or 111 In-oxine and were co-injected intranodally in melanoma patients under ultrasound guidance. In contrast to scintigraphic imaging, magnetic resonance imaging (MRI) allowed assessment of the accuracy of dendritic cell delivery and of inter- and intra-nodal cell migration patterns. MRI cell tracking using iron oxides appears clinically safe and well suited to monitor cellular therapy in humans.

This eye tracking experiment (N = 149) investigates the influence of different ways of disclosing brand placement on viewers' visual attention, the use of persuasion knowledge, and brand responses. The results showed that (1) a combination of text (\"This program contains product placement\") and a product placement (PP) logo was most effective in enhancing the recognition of advertising and that a logo alone was least effective; (2) this effect was mediated by viewers' visual attention to the disclosure and brand placement; and (3) the recognition of advertising consequently increased brand memory and led to more negative brand attitudes.