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991.
Trisha M. Wise-Draper Ganesh Moorthy Mohamad A. Salkeni Nagla Abdel Karim Hala Elnakat Thomas Carol A. Mercer M. Shalaan Beg Sue O’Gara Olugbenga Olowokure Hassana Fathallah Sara C. Kozma George Thomas Olivier Rixe Pankaj Desai John C. Morris 《Targeted oncology》2017,12(3):323-332
Background
The combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model.Objective
To establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed.Patients and Methods
BEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2.5 mg daily in 28-day cycles. Nineteen patients were enrolled. Adverse events and tumor responses were evaluated using CTCAE v4.0 and RECIST 1.1, respectively. Pharmacokinetic analyses were performed.Results
Common toxicities observed included fatigue, diarrhea, nausea, mucositis, and elevated liver enzymes. No confirmed responses were observed. BEZ235 pharmacokinetics exhibited dose-proportional increases in Cmax and AUC0-24 over the three doses, with high inter-individual variability. Non-compartmental and population pharmacokinetic-based simulations indicated significant increases in everolimus Cmax and AUC0-24 on day 28 and decreased clearance to 13.41 L/hr.Conclusions
The combination of BEZ235 and everolimus demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity. The changes in steady-state pharmacokinetics of everolimus with BEZ235 highlight potential drug–drug interactions when these two drugs are administered together.Clinicaltrials.gov: NCT01508104
992.
Slow Processing Speed Predicts Falls in Older Adults With a Falls History: 1‐Year Prospective Cohort Study 下载免费PDF全文
993.
Efficacy and safety of long‐acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery 下载免费PDF全文
994.
Reant P Lederlin M Lafitte S Serri K Montaudon M Corneloup O Roudaut R Laurent F 《European journal of radiology》2006,59(2):276-283
OBJECTIVE: The aims of this study were to investigate absolute assessment of aortic valve area (AVA), before surgery for aortic stenosis, using cardiovascular magnetic resonance (CMR) in comparison with transesophageal echocardiography (TEE) and with effective AVA indirectly obtained by routine techniques i.e. transthoracic echocardiography (TTE) and cardiac catheterisation. MATERIALS AND METHODS: Absolute AVA planimetry was performed by TEE and CMR steady state free precession sequences obtained through the aortic valvular plane. Effective AVA was calculated by the continuity equation in TTE and by cardiac catheterisation (Gorlin formula). RESULTS: Thirty-nine patients with aortic valve stenosis, mean age 71.7 +/- 7.6 years, with a mean AVA of 0.93 +/- 0.31 cm2 as measured by TEE, were enrolled in the study. Mean differences were: between CMR and TEE planimetry: d = 0.01 +/- 0.14 cm2, between CMR and cardiac catheterisation: d = 0.05 +/- 0.13 cm2, between CMR and TTE: d = 0.10 +/- 0.17 cm2, between TTE and TEE: d = 0.10 +/- 0.18 cm2, between TTE and cardiac catheterisation: d = 0.06 +/- 0.16 cm2, and between TEE and cardiac catheterisation: d = 0.07 +/- 0.13 cm2. Mean intraobserver and interobserver differences of CMR planimetry were d = 0.02 +/- 0.07 cm2 and d = 0.03 +/- 0.14 cm2, respectively. CONCLUSION: CMR planimetry of the AVA is a noninvasive and reproducible technique to evaluate stenotic aortic valves and can be used as an alternative to echocardiography or cardiac catheterisation. 相似文献
995.
Maffulli N Cook JL Khan KM 《The American journal of sports medicine》2006,34(8):1364; author reply 1364-1364; author reply 1365
996.
Rania Refaat Remon Zaher Elia Karim Omar ElSaeed 《The Egyptian Journal of Radiology and Nuclear Medicine》2013
Background
Comprehensive preoperative appraisal of potential living renal donors is the key for selecting a proper donor and a suitable kidney.Objective
To prospectively assess the diagnostic value of 16-slice multidetector computed tomography (MDCT) in preoperative appraisal of vascular anatomy in potential living renal donors.Materials and methods
Preoperative angiography using a 16-slice MDCT scanner was performed in 68 consecutive potential living renal donors. The MDCT angiography included unenhanced and contrast-enhanced multiphasic scans. The MDCT images were reviewed for the number and branching pattern of the renal arteries and for the number and presence of major or minor variants of the renal veins. The results were compared with the actual anatomy at the open donor nephrectomy as the diagnostic standard of reference.Results
The sensitivity and the specificity of MDCT angiography for the detection of various anatomic variants of renal arteries as well as renal venous anomalies were 100%. The anatomic variants of renal arteries included accessory arteries (n = 7) and early arterial branching (n = 10). Whereas, the detected venous anomalies were of major category of the circumaortic left renal vein anomaly (n = 2). No minor renal venous anomaly was identified in any subject.Conclusion
16-Slice MDCT angiography is highly accurate for preoperative assessment of diverse anomalies of the renal vascular anatomy in potential living renal donors; in consequence, it markedly affects the surgical planning. 相似文献997.
998.
Noboru Yamamoto Hiroshi Nokihara Yasuhide Yamada Kazunori Uenaka Risa Sekiguchi Takeshi Makiuchi Christopher A. Slapak Karim A. Benhadji Tomohide Tamura 《Cancer chemotherapy and pharmacology》2013,71(6):1645-1655
Purpose
LY2334737 is an oral gemcitabine prodrug. This Phase I study assessed the safety and tolerability of LY2334737 in Japanese patients with solid tumors and evaluated pharmacokinetics (PK), pharmacodynamics, and antitumor activity.Methods
Patients with advanced/metastatic solid tumors received escalating doses of LY2334737 once daily for 14 days, followed by a 7-day drug-free period. Cycles were repeated until discontinuation criteria were met.Results
Of 13 patients treated, 3 received 20 mg/day, 6 received 30 mg/day, 4 received 40 mg/day. On the 40 mg dose, 3 patients experienced dose-limiting toxicities (DLTs): hepatic toxicities (e.g., Grade [G]3/4 transaminase and G1–3 bilirubin elevation) and G4 thrombocytopenia; all 3 showed features of disseminated intravascular coagulation. One additional DLT occurred on the 30 mg dose (G3 transaminase elevation). Exploratory pharmacogenetic analyses identified a genetic variation in the CES2 gene potentially associated with these DLTs. PK data showed no clear relationship between the AUC of gemcitabine and its incorporation into leukocyte DNA; 2 of the 3 DLT patients had high incorporation. Two patients (30 mg/day) achieved stable disease with progression-free survival lasting 135 and 155 days.Conclusions
LY2334737 was tolerated by Japanese patients up to 30 mg/day. The toxicities observed at the 40 mg dose may require the development of alternative dosing schedules. 相似文献999.
Philippe Seguin Clara Locher Karim Boudjema Catherine Hamon Catherine Mouchel Yannick Malledant 《Nutrition and cancer》2016,68(3):464-472
Perioperative nutrition with supplements containing l-arginine, ω3-polyunsaturated fatty acids, and nucleotides could boost liver function recovery, immune response, and resistance to infection after hepatic resection. We conducted a placebo-controlled, randomized, double-blind study to assess the effect of a perioperative nutritional supplementation with Oral Impact® in patients undergoing hepatic surgery for liver cancer. Treatment was given three times daily for 7 days before and 3 days after surgery. Primary outcome was factor V, 3 days after surgery. Thirty-five patients (placebo: 17; Oral Impact: 18) were included. Five patients (placebo: three; Oral Impact: two) were not operated and five (placebo: two; Oral Impact: three) did not undergo hepatic resection. Factor V (mean ± SD) was 70 ± 27% and 79 ± 25% (P = 0.409) 3 days after surgery and 90 ± 30% and 106 ± 16% (P = 0.066) 5 days after surgery, in placebo and Oral Impact groups, respectively. There were no significant differences between groups on other outcomes assessing liver function recovery (bile production, γ-glutamyl transferase, α-fetoprotein), immune response (CD3, CD4, CD8 cells, CD4/CD8 ratio, natural killer cells, B lymphocytes), number of infections, and tolerance. A 10-day perioperative nutritional supplementation with Oral Impact does not improve hepatic function, immune response, and resistance to infection in patients undergoing hepatic surgery for liver cancer. 相似文献
1000.
Karim Jebari 《Medicine, health care, and philosophy》2016,19(1):95-101
Disease prioritarianism is a principle that is often implicitly or explicitly employed in the realm of healthcare prioritization. This principle states that the healthcare system ought to prioritize the treatment of disease before any other problem. This article argues that disease prioritarianism ought to be rejected. Instead, we should adopt ‘the problem-oriented heuristic’ when making prioritizations in the healthcare system. According to this idea, we ought to focus on specific problems and whether or not it is possible and efficient to address them with medical means. This has radical implications for the extension of the healthcare system. First, getting rid of the binary disease/no-disease dichotomy implicit in disease prioritarianism would improve the ability of the healthcare system to address chronic conditions and disabilities that often defy easy classification. Second, the problem-oriented heuristic could empower medical practitioners to address social problems without the need to pathologize these conditions. Third, the problem-oriented heuristic clearly states that what we choose to treat is a normative consideration. Under this assumption, we can engage in a discussion on de-medicalization without distorting preconceptions. Fourth, this pragmatic and de-compartmentalizing approach should allow us to reconsider the term ‘efficiency’. 相似文献