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Treatment and disease management patterns for bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer in North America,Europe and Asia:A real-world data analysis

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Current Urology 2022年第3期16卷 147-153页

作者： Edward I.Broughton Danielle S.Chun Kyna M.Gooden Katie L.Mycock Ivana Rajkovic gavin taylor-stokes WW Health Economics and Outcomes Research Bristol Myers SquibbPrincetonNJUSA The University of North Carolina Chapel HillNCUSA Observational Research Department Adelphi Real WorldBollingtonUK

Background:This study examined real-world treatment and management of bacillus Calmette-Guérin(BCG)-unresponsive patients across 3 continents,including patients unable or unwilling to undergo *** and methods:Physicians actively involved in managing patients with nonmuscle invasive bladder cancer completed online case report forms for their 5 consecutive patients from the broad BCG-unresponsive population and a further 5 consecutive BCG-unresponsive patients who did not undergo cystectomy(in Japan,physicians provided a total of 5 patients across both cohorts).Results:Most patients had received 1(37%)or 2(24%)maintenance courses of *** or more maintenance BCG courses were received by patients in Japan(59%)and China(31%),while in Germany 76%of patients received only 1 *** patients became BCG-unresponsive during their first(44%)or second(22%)treatment course;in Germany,77%became BCG-unresponsive during their first treatment *** countries did not provide another course of BCG after a patient first became unresponsive,whereas unresponsive patients in Japan and China were most likely to be retreated with BCG."Untreated-on watch and wait"was the main treatment/management approach received post-BCG treatment for 42%or more of patients in most countries except China(39%)and the United States(36%)."Following treatment guidelines"was consistently the top reason for post-BCG treatment selection across all treatment ***:This study confirmed the global unmet need for patients with nonmuscle invasive bladder cancer,and found that many patients experienced periods of no treatment after not responding to BCG therapy.

关键词： Bacillus Calmette-Guérin Bladder cancer Cystectomy Treatment failure Urinary tract

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Effect of nutritional counselling on hepatic,muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2006年第36期12卷 5813-5819页

作者： E Louise Thomas Audrey E Brynes gavin Hamilton Nayna Patel Adam Spong Robert D Goldin Gary Frost Jimmy D Bell Simon D taylor-Robinson The Robert Steiner MR Unit MRC Clinical Sciences Centre Department of Nutrition and Dietetics The Robert Steiner MR Unit MRC Clinical Sciences Centre Faculty of Medicine Imperial College London Hammersmith Hospital Du Cane Rd London W12 0HS United Kingdom and Histopathology Department Faculty of Medicine Imperial College London St Mary's Hospital Praed Street London W2 1NY United Kingdom Faculty of Medicine Faculty of Medicine Imperial College London St Mary's Hospital Praed Street London W2 1NY United Kingdom

AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.METHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease （NAFLD）.RESULTS： A 500 Kcal-restricted diet resulted in an average weight loss of 4% （-3.4 kg,） accompanied by significant reductions in most adipose tissue （AT） depots, including subcutaneous （-9.9%）, abdominal subcutaneous （-10.2%） and intra-abdominal- AT （-11.4%）. Intramyocellular lipids （IMCL） were significantly reduced in the tibialis muscle （-28.2%）. Decreases in both IHCL （-39.9%） and soleus IMCL （-12.2%） content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests： serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）. Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION： This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LETs.

关键词： Intra-abdominal adipose tissue Intrahepatic fat Intramyocellular lipids Weiqht loss Magnetic resonance imaging

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The Acute Physiological Effects of the Vaso-Active Drug, L-NNA, a Nitric Oxide Synthase Inhibitor, on Renal and Tumour Perfusion in Human Subjects

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Journal of Cancer Therapy 2014年第1期5卷 44-52页

作者： Kent Yip Vicky Goh Jane Gregory Ian Simcock J. James Stirling N. Jane taylor Robert Kozarski Andrew Mitchell Sam Bosopem gavin Halbert Roberto Alonzi David Miles Peter Hoskin Cancer Centre Mount Vernon Hospital Northwood UK Cancer Research UK Formulation Unit Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde Glasgow UK Department of Pscyhology University of Hertfordshire College Lane Hertfordshire UK Paul Strickland Scanner Centre Mount Vernon Hospital Northwood UK The Royal Brompton & Harefield NHS Foundation Trust Harefield UK

Purpose: To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selective inhibitor of nitric oxide synthase, L-NNA. Materials & Methods: Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. Results: L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood volume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%;renal BV—19.7%;tumour BF—16.9%;tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tumour within 1 hour following L-NNA (p 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. Conclusion: The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation.

关键词： L-NNA Cancer Imaging Vascular Perfusion Nitric Oxide

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RECENT PROGRESS IN INCOMPRESSIBLE REYNOLDSAVERAGED NAVIER-stokes SOLVERS

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Journal of Hydrodynamics 1996年第1期8卷 13-30页

作者： C. H. Sung T. T. Huang(David taylor Model Basin,CD/NSWC Bethesda, MD 20084- 5000,USA) David taylor Model Basin Bethesda United States

A new numerical approach based on a multiblock, multigrid, local refinement method has been developed. The multiblock structure makes grid generation for complex geometries easier,multigrid techniques significantly accelerate the rate of convergence and the local refinement method provides high spatial resolution of boundary lay6r and separated vortical flows with much reduced computer memory and CPU time. Sample three-dimensional flow computations for complex geometries are presented to illustrate the advantages in term of memory savings and reductions of CPU time in obtaining high spatial resolution solutions. High spatial resolution in the inner viscous layer is achieved by using the values of y+ for the first grid centers rom the wall in the order of 1 to 7. The required solution resolution in the dominantly viscous flow region (boundary layer, vortex core, or three-dimensional separated zone) dictates the acceptable spacing of grid cells in that region. It is very desirable to be able to reduce grid spacing locally in the critical region without changing the overall grid. The local refinement technique doubles grid numbers in all three directions for every level of refinement. Multiple levels of local grid refinement with moderate grid stretching can be used to provide fine grid spacing in rapidly changing flow regions such as near the wall, vortex core and separated shear layer. Thus, the method provides the required fine spatial resolution in the dominantly viscous region which is relatively small compared to the entire computational domain. This also avoids the used of excessively large aspect ratios of the grid cells near the rapidly changing now regions thus reduces truncation error and improves robustness. Furthermore, the results of numerical experimentation indicate that the present multigrid local refinement technique provides very effective numerical communications across the fine and coarse grid interfaces because the finer mesh is embedde

关键词： ultiblock multigrid local refinement

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