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91.
Rebecca M. Dodson Amin Firoozmand Omar Hyder Vania Tacher David P. Cosgrove Nikhil Bhagat Joseph M. Herman Christopher L. Wolfgang Jean-Francois H. Geschwind Ihab R. Kamel Timothy M. Pawlik 《Journal of gastrointestinal surgery》2013,17(12):2123-2132
Background
Assessment of patient performance status is often subjective. Sarcopenia—measurement of muscle wasting—may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT).Methods
Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors.Results
Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm2/m2) was greater than women (413 mm2/m2). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR?=?1.84) and Child's score (HR?=?2.15) (all P?<?0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR?=?1.84; P?=?0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients.Conclusions
Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies. 相似文献92.
93.
Pamela Leece Nikhil Rajaram Susan Woolhouse Margaret Millson 《Journal of urban health》2013,90(3):542-551
Among inner-city populations in Canada, the use of crack cocaine by inhalation is prevalent. Crack smoking is associated with acute respiratory symptoms and complications, but less is known about chronic respiratory problems related to crack smoking. There is also a gap in the literature addressing the management of respiratory disease in primary health care among people who smoke crack. The purpose of our study was to assess the prevalence of acute and chronic respiratory symptoms among patients who smoke crack and access primary care. We conducted a pilot study among 20 patients who currently smoke crack (used within the past 30 days) and who access the “drop-in clinic” at an inner-city primary health care center. Participants completed a 20- to 30-min interviewer-administered survey and provided consent for a chart review. We collected information on respiratory-related symptoms, diagnoses, tests, medications, and specialist visits. Data were analyzed using frequency tabulations in SPSS (version 19.0). In the survey, 95 % (19/20) of the participants reported having at least one respiratory symptom in the past week. Thirteen (13/19, 68.4 %) reported these symptoms as bothersome. Chart review indicated that 12/20 (60 %) had a diagnosis of either asthma or chronic obstructive pulmonary disease (COPD), and four participants (4/20, 20 %) had a diagnosis of both asthma and COPD. Majority of the participants had been prescribed an inhaled medication (survey 16/20, 80 %; chart 12/20, 60 %). We found that 100 % (20/20) of the participants currently smoked tobacco, and 16/20 (80 %) had smoked both tobacco and marijuana prior to smoking crack. Our study suggests that respiratory symptoms and diagnoses of asthma and COPD are prevalent among a group of patients attending an inner-city clinic in Toronto and who also smoke crack. The high prevalence of smoking tobacco and marijuana among our participants is a major confounder for attributing respiratory symptoms to crack smoking alone. This novel pilot study can inform future research evaluating the primary health care management of respiratory disease among crack smokers, with the aim of improving health and health care delivery. 相似文献
94.
95.
96.
Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma 总被引:1,自引:0,他引:1 下载免费PDF全文
Chauhan D Singh A Brahmandam M Podar K Hideshima T Richardson P Munshi N Palladino MA Anderson KC 《Blood》2008,111(3):1654-1664
Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 triggers apoptosis in multiple myeloma (MM) cells, and importantly, that is distinct from bortezomib (Velcade) in its chemical structure, effects on proteasome activities, and mechanisms of action. Here, we demonstrate that combining NPI-0052 and bortezomb induces synergistic anti-MM activity both in vitro using MM cell lines or patient CD138(+) MM cells and in vivo in a human plasmacytoma xenograft mouse model. NPI-0052 plus bortezomib-induced synergistic apoptosis is associated with: (1) activation of caspase-8, caspase-9, caspase-3, and PARP; (2) induction of endoplasmic reticulum (ER) stress response and JNK; (3) inhibition of migration of MM cells and angiogenesis; (4) suppression of chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) proteolytic activities; and (5) blockade of NF-kappaB signaling. Studies in a xenograft model show that low dose combination of NPI-0052 and bortezomib is well tolerated and triggers synergistic inhibition of tumor growth and CT-L, C-L, and T-L proteasome activities in tumor cells. Immununostaining of MM tumors from NPI-0052 plus bortezomib-treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Taken together, our study provides the preclinical rationale for clinical protocols evaluating bortezomib together with NPI-0052 to improve patient outcome in MM. 相似文献
97.
Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor 总被引:2,自引:1,他引:2 下载免费PDF全文
Bellucci R Alyea EP Chiaretti S Wu CJ Zorn E Weller E Wu B Canning C Schlossman R Munshi NC Anderson KC Ritz J 《Blood》2005,105(10):3945-3950
Donor lymphocyte infusions (DLIs) induce effective graft-versus-tumor responses in patients with multiple myeloma who relapse after allogeneic hematopoietic stem-cell transplantation. The graft-versus-myeloma response is presumably mediated primarily by donor T cells, but recent studies have also demonstrated the presence of antibodies specific for a variety of myeloma-associated antigens in patients who achieve complete remission after DLI. One of the B-cell antigens identified in these studies was B-cell maturation antigen (BCMA), a transmembrane receptor of the tumor necrosis factor (TNF) superfamily that is selectively expressed by mature B cells. The present studies were undertaken to characterize the functional significance of antibodies to BCMA in vivo. Using transfected cells expressing BCMA, antibodies in patient serum were found to react with the cell-surface domain of BCMA. Post-DLI patient serum was able to induce complement-mediated lysis and antibody-dependent cellular cytotoxicity (ADCC) of transfected cells and primary myeloma cells expressing BCMA. BCMA antibodies were only found in post-DLI responders and not in other allogeneic transplant patients or healthy donors. These results demonstrate that BCMA is a target of donor B-cell immunity in patients with myeloma who respond to DLI. Antibody responses to cell-surface BCMA may contribute directly to tumor rejection in vivo. 相似文献
98.
Hui Yu Zhengming Chen Karla V. Ballman Mark A. Watson Ramaswamy Govindan Irena Lanc David G. Beer Raphael Bueno Lucian R. Chirieac Michael Herman Chui Guoan Chen Wilbur A. Franklin David R. Gandara Carlo Genova Kristine A. Brovsky Mary-Beth M. Joshi Daniel T. Merrick William G. Richards Fred R. Hirsch 《Journal of thoracic oncology》2019,14(1):25-36
Objectives
Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.Methods
A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.Results
The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.Conclusions
Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells. 相似文献99.
100.
David M. Gilligan Antonios Marsonis Jayshree Joshi Stephen R. Bloom Celia M. Oakley Petros Nihoyannopoulos Mohammad A. Ghatei 《Clinical cardiology》1996,19(2):129-135
Some patients with hypertrophic cardiomyopathy experience postprandial exacerbation of symptoms. The aim of this study was to determine whether the hemodynamic and/or hormonal responses to a meal differ between patients with and without postprandial symptoms. Ten hypertrophic cardiomyopathy patients with postprandial symptoms, 10 patients without postprandial symptoms, and 10 normal subjects ate a 740 Kcal meal, following which heart rate, blood pressure, and echocardiographic and gastrointestinal hormone changes were compared among the three groups. Heart rate increased (p<0.001) and diastolic blood pressure fell (p < 0.001) to a similar degree in the three groups. Left ventricular outflow tract velocity increased (p< 0.01) and some patients had substantial increases in outflow tract pressure gradient; however, this was independent of the presence or absence of postprandial symptoms. The atrial contribution to filling increased in normal subjects and in both groups of hypertrophic cardiomyopathy patients. There was no significant difference in the gastrointestinal hormone changes in the three groups. In summary, there is no evidence for a distinctive hemodynamic or hormonal response to food in hypertrophic cardiomyopathy patients with postprandial symptoms. These symptoms more likely reflect differences in underlying cardiac disease characteristics and severity. 相似文献