Plasma N-Terminal Pro-Brain Natriuretic Peptide as Prognostic Marker in Fatal Cardial Decompensation with Sunitinib Malate Therapy

A 74-year-old man with metastatic renal cell carcinoma and a history of cardiac failure was treated with sunitinib malate. MUGA echocardiography could not detect a relevant change in the ejection fraction although the clinical situation of the patient worsened dramatically. The only parameter to hint at the deteriorated cardiac function was plasma N-terminal pro-brain natriuretic peptide (BNP). Finally, the patient died after only one cycle of sunitinib treatment. We propose to prospectively include BNP for the early detection of cardiovascular decompensation in high-risk patients. Future studies concerning the relevance of BNP in drug-related cardiotoxicity are urgently needed. Copyright (C) 2010 S. Karger AG, Base

Passivity, being-with and being-there: care during birth

This paper examines how to best be with women during birth, based on a phenomenological description of the birth experience. The first part of the paper establishes birth as an uncanny experience, that is, an experience that is not only entirely unfamiliar, but even unimaginable. The way in which birth happens under unknowable circumstances (in terms of when, how, with whom…) creates a set of anxieties on top of the fundamental anxiety that emerges from the existential paradox by which it does not seem possible for a body to give birth to another body. Would homebirth provide a remedy to the uncanniness? The result yielded by medical studies is confirmed by the phenomenological perspective taken here: homebirth might be reassuring for some, but not for everybody; choice of birth place is important. Once the birth process starts happening, another layer of strangeness is added: it turns out to be an experience of radical passivity and waiting, normally. The question thus becomes how to best care for somebody who is exposed to uncanniness, passivity, and waiting. Martin Heidegger’s concepts of care and discourse prove useful in examining how to facilitate rather than interrupt this process. It becomes necessary to think beyond verbal communication towards a wider concept of communication that involves silence and intercorporeality. Birth requires a special kind of being-with as being-there

Profile of temsirolimus in the treatment of advanced renal cell carcinoma

Temsirolimus is a potent inhibtor of the mammalian target of rapamycin (mTOR). In various clinical trials temsirolimus has shown an overall survival benefit for patients with metastatic renal cell carcinoma (mRCC). Thus it is approved for first-line therapy in high-risk mRCC patients. We discuss the indication, side effects and clinical implications of temsirolimus treatment

18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results

INTRODUCTION Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8~weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT

Between platonic love and internet pornography

The article sets out to show how an holistic approach in matters of sexuality is always more helpful than one-sided approaches. On the issue of internet pornography, the authors suggest that the recent anti-masturbation online movement ‘no fapping’ is based on wrong conclusions from insufficient evidence. We suggest that a holistic approach is called for, with emphasis on the embodied human. Abstinence or what is understood by ‘Platonic love’ is not a solution, according to Plato himself. From a phenomenological perspective, we suggest owning up to our strange bodies and habitualising sexual activity

68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results

BACKGROUND 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. RESULTS Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. CONCLUSION Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients

Optimized management of urolithiasis by coloured stent-stone contrast using dual-energy computed tomography (DECT)

Background We analysed in vitro the appearance of commonly used ureteral stents with dual-energy computed tomography (DECT) and we used these characteristics to optimize the differentiation between stents and adjacent stone. Methods We analysed in vitro a selection of 36 different stents from 7 manufacturers. They were placed in a self-build phantom model and measured using the SOMATOM® Force Dual Source CT-Scanner (Siemens, Forchheim, Germany). Each sample was scanned at various tube potentials of 80 and 150 peak kilovoltage (kVp), 90 and 150 kVp and 100 and 150 kVp. The syngo Post-Processing Suite software program (Siemens, Forchheim, Germany) was used for differentiation based on a 3–material decomposition algorithm (UA, calcium, urine) according to our standard stone protocol. Results Stents composed of polyurethane appeared blue and silicon-based stents were red on the image. The determined appearances were constant for various peak kilovoltage (kVp) values. The coloured stent-stone-contrast displayed on DECT improves monitoring, especially of small calculi adjacent to indwelling ureteral stents. Conclusion Both urinary calculi and ureteral stents can be accurately differentiated by a distinct appearance on DECT. For the management of urolithiasis patients can be monitored more easily and accurately using DECT if the stent shows a different colour than the adjacent stone

Рекомендации по лечению пациентов с прогрессирующим или метастатическим почечно-клеточным раком комбинацией ленватиниба и эверолимуса

.На сегодняшний день существует несколько вариантов терапии 2-й линии для пациентов с почечно-клеточным раком после неудачи 1-й линии терапии ингибиторами тирозинкиназ. Недавно были одобрены для лечения кабозантиниб, ниволумаб и комбинация ленватиниб + эверолимус. Отсутствие надежных биомаркеров, а также ограниченность данных проспективных сравнений различных препаратов затрудняют выбор тактики лечения 2-й линии в рутинной клинической практике.В настоящем обзоре мы описываем профиль безопасности комбинации ленватиниб + эверолимус при почечно-клеточном раке. Данная комбинация обеспечила наиболее высокие показатели объективного ответа на терапию, выживаемости без прогрессирования и общей выживаемости в исследованиях с перекрестным дизайном. В то же время профиль безопасности этой комбинации, включая частоту общих и тяжелых нежелательных явлений, процент пациентов, которым потребовалось снижение дозы или полная отмена лечения, был менее благоприятным по сравнению с доступными вариантами монотерапии. Это позволяет предположить, что более тщательный контроль токсических реакций может способствовать достижению максимальной активности этих двух средств, одновременно защищая пациентов от неоправданного вреда.Цель — разработка междисциплинарных рекомендаций для пациентов и лиц, осуществляющих уход за ними, перед началом лечения комбинацией ленватиниб + эверолимус, в том числе по контролю терапии с точки зрения повседневной клинической практики.Основные положения:•             Комбинация ленватиниба и эверолимуса одобрена для лечения пациентов с почечно-клеточным раком, рефрактерным к терапии ингибиторами тирозинкиназ, на основании высоких показателей объективного ответа, длительной выживаемости без прогрессирования и общей выживаемости.•             Профиль безопасности этой комбинации включает высокую частоту общих и тяжелых нежелательных явлений, при этом многие пациенты нуждаются в снижении дозы или прекращении лечения. Это позволяет предположить, что более эффективный контроль токсических реакций может способствовать достижению максимальной активности комбинации препаратов, одновременно защищая пациентов от неоправданного вреда.•             В этой статье мы представили мультидисциплинарные рекомендации по консультированию пациентов и лиц, осуществляющих уход за ними, перед началом лечения ленватинибом в комбинации с эверолимусом, в том числе по контролю терапии с точки зрения повседневной клинической практики.Публикуется на русском языке с разрешения авторов. Оригинал: Grande E., Glen H., Aller J. et al. Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma. Expert Opinion on Drug Safety 2017. DOI: 10.1080/14740338.2017.1380624

Two-dimensional finite element simulation of fracture and fatigue behaviours of alumina microstructures for hip prosthesis

This paper describes a two-dimensional (2D) finite element simulation for fracture and fatigue behaviours of pure alumina microstructures such as those found at hip prostheses. Finite element models are developed using actual Al2O3 microstructures and a bilinear cohesive zone law. Simulation conditions are similar to those found at a slip zone in a dry contact between a femoral head and an acetabular cup of hip prosthesis. Contact stresses are imposed to generate cracks in the models. Magnitudes of imposed stresses are higher than those found at the microscopic scale. Effects of microstructures and contact stresses are investigated in terms of crack formation. In addition, fatigue behaviour of the microstructure is determined by performing simulations under cyclic loading conditions. It is shown that crack density observed in a microstructure increases with increasing magnitude of applied contact stress. Moreover, crack density increases linearly with respect to the number of fatigue cycles within a given contact stress range. Meanwhile, as applied contact stress increases, number of cycles to failure decreases gradually. Finally, this proposed finite element simulation offers an effective method for identifying fracture and fatigue behaviours of a microstructure provided that microstructure images are available