Process for producing high strength alumina

A vacuum hot pressed alumina material having small, isometric grains; a uniform distribution thereof; relatively low, predominantly transgranular porosity; and a density approaching the theoretical density of pure alumina produced by vacuum hot pressing alumina powder which contains at least 98.0% alumina, is substantially free of any sintering aids or any other additives, and has a median particle size less than about 3 microns, in a vacuum hot press operated at a temperature of at least about 1350° C. and a pressure of at least 28 MPa (3500 PSI) for a sintering period of at least 1.5 hours. The vacuum hot pressed alumina material also has compressive strength, flexural strength, impact strength, and wear resistance superior to that for most conventional sintered alumina materials.https://digitalcommons.mtu.edu/patents/1072/thumbnail.jp

High strength alumina and process for producing same

A vacuum hot pressed alumina material having small, isometric grains; a uniform distribution thereof; relatively low, predominantly transgranular porosity; and a density approaching the theoretical density of pure alumina produced by vacuum hot pressing alumina powder which contains at least 98.0% alumina, is substantially free of any sintering aids or any other additives, and has a median particle size less than about 3 microns, in a vacuum hot press operated at a temperature of at least about 1350° C. and a pressure of at least 28 MPa (3500 PSI) for a sintering period of at least 1.5 hours. The vacuum hot pressed alumina material also has compressive strength, flexural strength, impact strength, and wear resistance superior to that for most conventional sintered alumina materials.https://digitalcommons.mtu.edu/patents/1075/thumbnail.jp

Polyethylene glycol-coated collagen patch (hemopatch®) in open partial nephrectomy

PURPOSE To describe the results of a polyethylene glycol-coated collagen patch, Hemopatch® on blood loss, surgical time and renal function in partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS Out of a single surgeon cohort of n = 565 patients undergoing conventional open PN (CPN) between 01/2015 and 12/2017 at the University of Munich a consecutive subgroup (n = 42) was operated on using a polyethylene glycol-coated collagen-based sealant Hemopatch® (Baxter International Inc., Deerfield, IL, USA) (HPN). RESULTS Median age was 65.2~years (range 12.7-95.2) with median follow-up of 9.43~months (0.03-49.15). Baseline renal function (CKD-EPI) was 78.56~ml/min/1.73~m2 (range 20.38-143.09) with a non-significant decline to 74.78~ml/min/1.73~m2 (range 3.75-167.74) at follow-up. In CPN 46% had low complexity, 33% moderate complexity and 20% high complexity lesions with 33% low, 40% moderate and 27% high complexity masses in HPN. Median tumor size was 4.3~cm (range 1-38~cm) in CPN with 4.8~cm (range 3.8-18.3~cm) with HPN, p = 0.293. Median blood loss and duration of surgery was significantly lower in the HPN group vs. CPN (146~ml ± 195 vs. 114~ml ± 159~ml; p = 0.021; 43~min ± 27 for HPN vs. 53~min ± 49; p = 0.035) with no difference in clamping time (12.6~min ± 8.6 for HPN vs. 12.0~min ± 9.5; p = 0.701). CONCLUSIONS Hemopatch® supported renoraphy shows promising results compared to standard renoraphy in PN. No side effects were seen. Further studies should evaluate the prevention of arterio-venous or urinary fistulas. In complex partial nephrectomies Hemopatch® supported renoraphy should be considered

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

Trends in COVID-19-associated mortality in patients with pulmonary hypertension: a COMPERA analysis

In patients with pulmonary hypertension, the mortality rate associated with COVID-19 has declined sharply with the emergence of the Omicron variants https://bit.ly/42OMsf

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

Management of Sporadic Renal Angiomyolipomas: A Systematic Review of Available Evidence to Guide Recommendations from the European Association of Urology Renal Cell Carcinoma Guidelines Panel

CONTEXT: Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options. OBJECTIVE: To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice. EVIDENCE ACQUISITION: A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of follow-up. Risk of bias assessment was performed using standard Cochrane methods. EVIDENCE SYNTHESIS: Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias. CONCLUSIONS: In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in terms of recurrence and need for secondary procedures. Thermal ablation was an infrequent option. The association between AML size and the risk of bleeding remained unclear; as such the traditional 4-cm cut-off should not per se trigger active treatment. In spite of the limitations and uncertainties relating to the evidence base, the findings may be used to guide and inform clinical practice, until more robust data emerge. PATIENT SUMMARY: Sporadic angiomyolipoma (AML) is a benign tumour of the kidney consisting of a mixture of blood vessels, fat, and muscle. Large tumours may have a risk of spontaneous bleeding. However, the size beyond which these tumours need to be treated remains unclear. Most small AMLs can be monitored without any active treatment. For those who need treatment, options include surgical removal of the tumour or stopping its blood supply (selective embolisation). Surgery has a lower recurrence rate and lower need for a repeat surgical procedure

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

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

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