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1.
Victoria L. Parker Matthew C. Winter John A. Tidy Barry W. Hancock Julia E. Palmer Naveed Sarwar Baljeet Kaur Katie McDonald Xianne Aguiar Kamaljit Singh Nick Unsworth Imran Jabbar Allan A. Pacey Robert F. Harrison Michael J. Seckl 《International journal of cancer. Journal international du cancer》2023,152(5):986-997
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus. 相似文献
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Margaret H. Lauerman Karen Irizarry Clint Sliker Brandon R. Bruns Ronald Tesoriero Thomas M. Scalea Deborah M. Stein 《Injury》2019,50(1):131-136
Background
Current blunt cerebrovascular injury (BCVI) grading grossly differentiates injury characteristics such as luminal stenosis (LS) and aneurysmal disease. The effect of increasing degree of LS beyond the current BCVI grading scale on stroke formation is unknown.Study Design
BCVI over a 3-year period were retrospectively reviewed. To investigate influence of LS beyond the BCVI grading scale within aneurysmal and non-aneurysmal BCVI, grade 2 BCVI were subdivided into BCVI with ≥ 25% and ≤ 50% LS and BCVI with > 50% and ≤ 99% LS. Grade 3 BCVI were subdivided into BCVI with pseudoaneurysm (PSA) without LS and BCVI with PSA and LS. We hypothesized increased LS beyond the current BCVI grade distinctions would be associated with higher rates of stroke formation.Results
312 BCVI were included, of which 140 were carotid BCVI and 172 vertebral BCVI. Sixteen carotid BCVI underwent endovascular intervention (EI) and 19 suffered a stroke. In carotid BCVI stroke rates increased sequentially with BCVI grade except in grade 3. There was a stroke rate of 12% in grade 1 carotid BCVI, 18% in grade 2, 6% in grade 3, and 31% in grade 4. In subgroup analysis for grade 2 carotid BCVI, BCVI with > 50% and ≤ 99% LS had higher rates of stroke (22% vs. 15%, p?=?0.44) than BCVI with ≥ 25% and ≤ 50% LS. In subgroup analysis of grade 3 carotid BCVI, BCVI with PSA and LS had higher rates of stroke (9% vs. 4%, p?=?0.48) than BCVI with PSA without LS. Higher rates of EI in grade 2 carotid BCVI with > 50% and ≤ 99% LS (22% vs. 5%, p?=?0.14) and grade 3 carotid BCVI with PSA and LS (35% vs. 4%, p?=?0.01) were noted in subgroup analysis.Conclusion
Higher percentage LS beyond the currently used BCVI grading scale has a non-significantly increased rate of stroke in both aneurysmal and non-aneurysmal BCVI. Grade 3 BCVI with PSA and LS seems to be a high-risk subgroup. Use of EI confounds modern measurement of stroke risk in higher LS BCVI. 相似文献7.
Ramya Deepthi Vinnakota Allan S. Brett 《The American journal of the medical sciences》2019,357(2):160-163
Iron deficiency anemia is often listed among potential adverse effects of gastric acid-suppressive medications, given that gastric acidity promotes intestinal absorption of nonheme iron. Additionally, the antacid calcium carbonate can inhibit iron absorption. However, there is little direct clinical evidence that proton-pump inhibitors, histamine-2 receptor antagonists, or calcium carbonate cause iron deficiency anemia. Most case reports have had substantial limitations (e.g., minimal follow-up and presence of other causes of iron deficiency), and retrospective cohort studies have lacked sufficient patient-specific detail to make strong causal inferences. We present 2 cases—both with detailed, prospective 10-year follow-up—in which combinations of proton-pump inhibitors, histamine-2 receptor antagonists and calcium carbonate were clearly associated with development of iron deficiency anemia. Overt iron-deficiency anemia is probably uncommon in patients who use acid-modifying medications and who have no other conditions that predispose to iron deficiency. Nevertheless, clinicians should be aware of this potential complication, given widespread use of these agents. 相似文献
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William B. Parker Paula W. Allan William R. Waud Jeong Hong Melissa Gilbert-Ross B. R. Achyut Disha Joshi Turang Behbahani Regina Rab Steven E. Ealick Eric J. Sorscher 《Cancer chemotherapy and pharmacology》2020,85(3):573-583
Treatment with fludarabine phosphate (9-β-D-arabinofuranosyl-2-F-adenine 5′-phosphate, F-araAMP) leads to regressions and cures of human tumor xenografts that express Escherichia coli purine nucleoside phosphorylase (EcPNP). This occurs despite the fact that fludarabine (F-araA) is a relatively poor substrate for EcPNP, and is cleaved to liberate 2-fluoroadenine at a rate only 0.3% that of the natural E. coli PNP substrate, adenosine. In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show that Trichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypic E. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressing TvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressing EcPNP, although much less enzyme was expressed per cell in the TvPNP transduced condition. As a test of safety and efficacy using TvPNP, human head and neck squamous cell carcinoma (FaDu) xenografts expressing TvPNP were studied in nude mice and shown to exhibit robust tumor regressions, albeit with partial weight loss that resolved post-therapy. F-araAMP was also a very effective treatment for mice bearing D54/TvPNP xenografts in which approximately 10% of tumor cells expressed the enzyme, indicating pronounced ability to kill non-transduced tumor cells (high bystander activity). Moreover, F-araAMP demonstrated activity against D54 tumors injected with an E1, E3 deleted adenoviral vector encoding TvPNP. In that setting, despite higher F-araA cleavage activity using TvPNP, tumor responses were similar to those obtained with EcPNP, indicating factors other than F-Ade production may limit regressions of the D54 murine xenograft model. Our results establish that TvPNP is a favorable enzyme for activating F-araA, and support further studies in combination with F-araAMP for difficult-to-treat human cancers. 相似文献