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排序方式: 共有356条查询结果,搜索用时 15 毫秒
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Non‐peptide‐based new class of platelet aggregation inhibitors: Design,synthesis, bioevaluation,SAR, and in silico studies 下载免费PDF全文
Pradeep K. Jaiswal Vashundhra Sharma Surendra Kumar Manas Mathur Ajit K. Swami Dharmendra K. Yadav Sandeep Chaudhary 《Archiv der Pharmazie》2018,351(3-4)
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David Hausner Colombe Tricou Jean Mathews Deepa Wadhwa Ashley Pope Nadia Swami Breffni Hannon Gary Rodin Monika K. Krzyzanowska Lisa W. Le Camilla Zimmermann 《The oncologist》2021,26(4):332-340
BackgroundEvidence from randomized controlled trials has demonstrated benefits in quality of life outcomes from early palliative care concurrent with standard oncology care in patients with advanced cancer. We hypothesized that there would be earlier referral to outpatient palliative care at a comprehensive cancer center following this evidence.Materials and MethodsAdministrative databases were reviewed for two cohorts of patients: the pre‐evidence cohort was seen in outpatient palliative care between June and November 2006, and the post‐evidence cohort was seen between June and November 2015. Timing of referral was categorized, according to time from referral to death, as early (>12 months), intermediate (>6 months to 12 months), and late (≤6 months from referral to death). Univariable and multivariable ordinal logistic regression analyses were used to determine demographic and medical factors associated with timing of referral.ResultsLate referrals decreased from 68.8% pre‐evidence to 44.8% post‐evidence; early referrals increased from 13.4% to 31.1% (p < .0001). The median time from palliative care referral to death increased from 3.5 to 7.0 months (p < .0001); time from diagnosis to referral was also reduced (p < .05). On multivariable regression analysis, earlier referral to palliative care was associated with post‐evidence group (p < .0001), adjusting for shorter time since diagnosis (p < .0001), referral for pain and symptom management (p = .002), and patient sex (p = .04). Late referrals were reduced to <50% in the breast, gynecological, genitourinary, lung, and gastrointestinal tumor sites.ConclusionsFollowing robust evidence from trials supporting early palliative care for patients with advanced cancer, patients were referred substantially earlier to outpatient palliative care.Implications for PracticeFollowing published evidence demonstrating the benefit of early referral to palliative care for patients with advanced cancer, there was a substantial increase in early referrals to outpatient palliative care at a comprehensive cancer center. The increase in early referrals occurred mainly in tumor sites that have been included in trials of early palliative care. These results indicate that oncologists’ referral practices can change if positive consequences of earlier referral are demonstrated. Future research should focus on demonstrating benefits of early palliative care for tumor sites that have tended to be omitted from early palliative care trials. 相似文献
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Varinder Kaur Arjun Swami Daisy Alapat Al Ola Abdallah Pooja Motwani Laura F. Hutchins 《Hematology (Amsterdam, Netherlands)》2018,23(1):17-24
Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002–2015).Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n?=?19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n?=?12), 35% for CD68 (n?=?8), 30% for CD34 (n?=?7), and 26% for lysozyme (n?=?6). Cytogenetic abnormalities were seen in 63% (n?=?12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n?=?3) or monosomal (n?=?2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4–24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p?=?0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p?0.001). All patients who underwent allogeneic hematopoietic stem cell transplant attained long-term remissions, with a median follow-up of 54 (range 32–120) months.Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions. 相似文献
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Dynamic contrast material-enhanced magnetic resonance (MR) imaging has emerged as a valuable tool in evaluation of women who have undergone lumpectomy and whole-breast radiation therapy for breast cancer. Early diagnosis of local recurrence by means of close clinical and imaging follow-up is an important component of a breast-conserving strategy, as it may improve survival. In the post-breast conservation therapy (BCT) breast, resolving edema, fat necrosis, a small focal area of non-masslike enhancement (NMLE), and thin linear NMLE at the lumpectomy site can all be expected findings. In contrast, masslike enhancement or NMLE of ductal or segmental distribution can indicate recurrence. Therefore, at MR imaging of the post-BCT breast, it is important to identify lesions that are benign or appropriate for short-interval imaging surveillance to minimize unnecessary intervention, as well as to discern suspicious lesions and optimize the diagnosis of recurrence. 相似文献
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Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131 下载免费PDF全文
Birkus G Wang R Liu X Kutty N MacArthur H Cihlar T Gibbs C Swaminathan S Lee W McDermott M 《Antimicrobial agents and chemotherapy》2007,51(2):543-550
GS-7340 and GS-9131 {9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]-propyl]adenine and 9-(R)-4'-(R)-[[[(S)-1-[(ethoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]-2'-fluoro-1'-furanyladenine, respectively} are novel alkylalaninyl phenyl ester prodrugs of tenofovir {9-R-[(2-phosphonomethoxy)propyl]adenine} (TFV) and a cyclic nucleotide analog, GS-9148 (phosphonomethoxy-2'-fluoro-2', 3'-dideoxydidehydroadenosine), respectively. Both prodrugs exhibit potent antiretroviral activity against both wild-type and drug-resistant human immunodeficiency virus type 1 strains and excellent in vivo pharmacokinetic properties. In this study, the main enzymatic activity responsible for the initial step in the intracellular activation of GS-7340 and GS-9131 was isolated from human peripheral blood mononuclear cells and identified as lysosomal carboxypeptidase A (cathepsin A [CatA]; EC 3.4.16.5). Biochemical properties of the purified hydrolase (native complex and catalytic subunit molecular masses of 100 and 29 kDa, respectively; isoelectric point [pI] of 5.5) matched those of CatA. Recombinant CatA and the isolated prodrug hydrolase displayed identical susceptibilities to inhibitors and identical substrate preferences towards a panel of tenofovir phosphonoamidate prodrugs. Incubation of both enzymes with 14C-labeled GS-7340 or [3H]difluorophosphonate resulted in the covalent labeling of identical 29-kDa catalytic subunits. Finally, following a 4-h incubation with GS-7340 and GS-9131, the intracellular concentrations of prodrug metabolites detected in CatA-negative fibroblasts were approximately 7.5- and 3-fold lower, respectively, than those detected in normal control fibroblasts. Collectively, these data demonstrate the key role of CatA in the intracellular activation of nucleotide phosphonoamidate prodrugs and open new possibilities for further improvement of this important class of antiviral prodrugs. 相似文献