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11.
Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. 总被引:11,自引:0,他引:11
Andre Goy Anas Younes Peter McLaughlin Barbara Pro Jorge E Romaguera Frederick Hagemeister Luis Fayad Nam H Dang Felipe Samaniego Michael Wang Kristine Broglio Barry Samuels Frederic Gilles Andreas H Sarris Susan Hart Elizabeth Trehu David Schenkein Fernando Cabanillas Alma M Rodriguez 《Journal of clinical oncology》2005,23(4):667-675
PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents. 相似文献
12.
Magdy Younes Bethany Gerardy Allan I Pack Samuel T Kuna Cecilia Castro-Diehl Susan Redline 《Sleep》2022,45(6)
Study ObjectivesConventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics.MethodsWe analyzed records from the Sleep-Heart-Health-Study and a study of performance deficit following sleep deprivation. ORP of all 30-second epochs in each PSG and percent of epochs in each decile of ORPs range were calculated. Percentage of epochs in deep sleep (ORP < 0.50) and in full-wakefulness (ORP > 2.25) were each assigned a rank, 1–3, representing first and second digits, respectively, of nine distinct types (“1,1”, “1,2” … ”3,3”). Prevalence of each type in clinical groups and their associations with demographics, sleepiness (Epworth-Sleepiness-Scale, ESS) and quality of life (QOL; Short-Form-Health-Survey-36) were determined.ResultsThree types (“1,1”, “1,2”, “1,3”) were prevalent in OSA and were associated with reduced QOL. Two (“1,3” and “2,3”) were prevalent in insomnia with short-sleep-duration (insomnia-SSD), but only “1,3” was associated with poor sleep depth and reduced QOL, suggesting two phenotypes in insomnia-SSD. ESS was high in types “1,1” and “1,2”, and low in “1,3” and “2,3”. Prevalence of some types increased with age while in others it decreased. Other types were either rare (“1,1” and “3,3”) or high (“2,2”) at all ages.ConclusionsThe proposed ORP histogram offers specific and unique information on the underlying neurophysiological characteristics of sleep disorders not captured by routine metrics, with potential of advancing diagnosis and management of these disorders. 相似文献
13.
Nicole Fakhoury Sayegh Gessica N. H. A. Heraoui Hassan Younes Lea Nicole Sayegh Christa Boulos Raymond Sayegh 《Nutrients》2022,14(12)
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis. 相似文献
14.
Russell A. Faust Adrien J. Kant Attila Lorincz Abbas Younes Elizabeth Dawe Michael D. Klein 《Journal of robotic surgery》2007,1(1):75-83
Minimally invasive surgery is rapidly becoming the desired surgical standard, especially for pediatric patients. Infants and
children are a particular technical challenge, however, because of the small size of target anatomical structures and the
small surgical workspace. Computer-assisted robot-enhanced surgical telemanipulators may overcome these challenges by facilitating
surgery in a small workspace. We studied the feasibility of performing robotic endoscopic neck surgery on a porcine model
of the human infant neck. The study design was a prospective, feasibility pilot study of a small cohort for proof of concept
and for a survival model. Sixteen non-survival piglets weighing 4.5–10 kg were used to develop the surgical approach and operative
technique. Eight piglets aged 3–6 weeks old and weighing 4.0–9.1 kg underwent survival thyroidectomy by a cervical endoscopic
approach using the Zeus surgical robot, which includes the Aesop endoscope holder and “Microwrist” microdissecting instruments.
We succeeded in performing endoscopic robotic neck surgery on a piglet as small as 4 kg, in an operative pocket as small as
2 cm3. Total incision length for all three ports was ≤23 mm. There were no major complications, no major robotic instrument malfunctions
or breakages, and no procedures required conversion to open surgery. These results support the feasibility of robotic endoscopic
neck surgery on a neck the size of a human infant’s.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. 相似文献
15.
Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea 总被引:9,自引:0,他引:9
Younes M 《American journal of respiratory and critical care medicine》2003,168(6):645-658
The contributions of pharyngeal mechanical abnormalities, flow demand, and compensatory effectiveness to obstructive sleep apnea severity were determined in 82 patients. Flow demand was estimated from mean inspiratory flow on continuous positive airway pressure. Mechanical load on upper airway muscles was estimated from minimal effective continuous positive airway pressure, flow demand, and minimum flow observed during brief pressure dial downs. Compensatory effectiveness was estimated by relating polysomnographic severity and mechanical load. Mechanical load was more severe in men, in supine position, and in older and heavier patients. Higher flow demand contributed significantly to mechanical load in men and in those who are obese. At the same mechanical load, severity was independent of age, sex, or body mass index but was greater in the supine position and in REM sleep. Mechanical load accounted for only 34% of variability in severity. Eighty-two percent of patients experienced periods of stable breathing despite mechanical loads that would produce continuous cycling without compensation. I conclude that most patients can adequately compensate for the abnormal mechanics, at least part of the time. Higher flow demand contributes to severity in men and in obesity. Severity is largely due to factors other than mechanical load. Compensatory effectiveness is impaired in the supine position and in REM sleep, but not by age, sex, or body mass index. 相似文献
16.
M Younes A Puddy D Roberts R B Light A Quesada K Taylor L Oppenheimer H Cramp 《The American review of respiratory disease》1992,145(1):121-129
The response to proportional assist ventilation (PAV) was tested in four normal subjects during heavy exercise and in five ventilator-dependent patients recovering from assorted medical disorders. The apparatus consisted of a rolling-seal piston coupled to a motor that generated pressure in proportion to inspired flow and inspired volume, with the gains adjusted such that the proportionality between airway pressure (Paw) and instantaneous patient-generated pressure (Pmus) was approximately 1:1 (i.e., machine-amplified patient effort by a factor of 2). Normal subjects responded to PAV by decreasing their own effort, as judged from esophageal pressure, such that the changes in ventilation and breathing pattern were rather small (VE: 64.8 +/- 3.6 during PAV versus 56.0 +/- 4.3, p less than 0.01; VT: 2.39 +/- 0.24 versus 2.02 +/- 0.17, p less than 0.05; f: 27.5 +/- 1.9 versus 28.0 +/- 2.2, NS). In patients, elastance ranged from 20 to 35 cm H2O cm/L, resistance ranged from 5 to 10 cm H2O/L/s, and maximal inspiratory pressure ranged from -16 to -65 cm H2O. After a period of observation during synchronized intermittent mechanical ventilation (SIMV) the patient was switched to PAV and maintained on it for 1 to 3 h. No patient had to be replaced on SIMV because of discomfort or deterioration in any of the monitored variables. During PAV peak airway pressure was less than half the value observed with the IMV breaths (16.6 +/- 2.4 versus 35.4 +/- 3.4 cm H2O, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
17.
18.
Perforation of the atretic pulmonary valve. Long-term follow-up 总被引:5,自引:0,他引:5
Agnoletti G Piechaud JF Bonhoeffer P Aggoun Y Abdel-Massih T Boudjemline Y Le Bihan C Bonnet D Sidi D 《Journal of the American College of Cardiology》2003,41(8):1399-1403
OBJECTIVES: We evaluated the long-term results of perforation of the pulmonary valve in patients with pulmonary atresia with an intact ventricular septum (PA-IVS). BACKGROUND: Interventional perforation of the pulmonary valve is considered the elective first stage treatment for PA-IVS, particularly in patients with a tripartite right ventricle (RV) and normal coronary circulation. However, the long-term results of this procedure are lacking. METHODS: Between January 1991 and December 2001, 39 newborns with a favorable form of PA-IVS underwent attempted perforation of the pulmonary valve. We evaluated the early and long-term outcomes. RESULTS: Median tricuspid and pulmonary z values were -1.2 and -2.4, respectively. Perforation was successful in 33 patients. Among them, 17 needed neonatal surgery, 13 did not need any surgery, and 3 had elective surgery after the first month of life. There were two procedure-related deaths, seven nonfatal procedural complications, and four postsurgical deaths. Compared with patients needing neonatal surgery, those having no or elective surgery had a higher incidence of a tripartite RV and a higher median tricuspid z value (92% vs. 53%, p = 0.04 and -1.7 vs. -0.5, p = 0.03). At a median follow-up of 5.5 years (range 0.5 to 11.5), survival was 85% and freedom from surgery was 35%. Five patients, four of whom had neonatal surgery, underwent a partial cavo-pulmonary connection. CONCLUSIONS: Our results show that this technique, although burdened by non-negligible mortality and morbidity, is effective in selected patients with a normal-sized RV. Preselection of patients allows interventional or surgical biventricular correction in the majority of cases. 相似文献
19.
20.
Younes El-Kardi Ali Jafri Amal Anide Abdelfettah Derouiche 《Nutrition Clinique et Métabolisme》2018,32(1):33-36