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Guillermo Garcia-Manero Antonio Almeida Pierre Fenaux Norbert Gattermann Aristoteles Giagounidis Stuart L. Goldberg Keiya Ozawa Jerry Weaver Valeria Santini 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(4):213-219.e4
BackgroundIn the phase III MDS-005 study of patients with lower-risk, non-del(5q) myelodysplastic syndromes, lenalidomide was associated with a higher rate of ≥ 8 weeks red blood cell transfusion independence (RBC-TI) compared with placebo, but also with a higher risk of hematologic adverse events (AEs).Patients and MethodsThis analysis evaluated the ratio of clinical benefit-risk in patients treated with lenalidomide or placebo, and assessed the effect of lenalidomide dose reductions on response. Clinical benefit was a composite endpoint defined as RBC-TI, transfusion reduction ≥ 4 units packed red blood cells, hemoglobin increase ≥ 1.5 g/dL, or cytogenetic response.ResultsThe rate of clinical benefit was higher with lenalidomide than with placebo (31.9% vs. 3.8%). The ratio of response (RBC-TI and clinical benefit) to risk (hematologic AEs) favored lenalidomide over placebo. Patients who underwent ≥ 1 lenalidomide dose reduction had a longer duration of treatment, received a higher cumulative dose, and were more likely to experience clinical benefit versus patients without dose reductions.ConclusionDespite the occurrence of hematologic AEs, the overall benefit-risk profile supported lenalidomide treatment. Appropriate management of hematologic AEs by dose reductions may help patients with myelodysplastic syndromes to remain on treatment and achieve clinical benefit. 相似文献
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Fernández RM Navarro E Antiñolo G Ruiz-Ferrer M Borrego S 《International journal of molecular medicine》2006,17(4):575-581
Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer syndrome, which is divided into three subtypes: MEN 2A, MEN 2B and familial medullary thyroid cancer (FMTC). Approximately 92% of MEN 2 cases are caused by mutations in exons 10, 11, 13-16 of the RET proto-oncogene. There exists inter- and intra-familial phenotypic variability among the MEN 2 families, even when the disease is caused by the same RET mutation, suggesting a role for genetic modifiers, such as polymorphisms/haplotypes. We have sought to determine the frequency and position of RET germline mutations in a cohort of 114 Spanish probands with any sign of MEN 2, and to search for putative modifier loci. Mutational screening of RET revealed 9 different mutations, present in 26 of the 114 probands (22.8%). In addition, distributions of 8 RET polymorphisms and the haplotypes comprising them, were studied in the context of the families positive for RET mutational screening, in order to evaluate them as genetic modifiers. The relationship between RET mutation type and presence of a polymorphism/haplotype was analyzed. The relationship between the presence of pheochromocytoma (PC) and/or hiperparathyroidism (HPT) in carriers of the same RET mutation, and the genotype for the specific variants was also studied. The results derived from those analyses revealed no associations of any variant/haplotype to a specific mutation or to the clinical presentation. Nevertheless, these observations do not permit us to exclude the possible role of other variants in RET or other related genes, in the final presentation of the disease. 相似文献
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Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella bronchiseptica variant producing reduced amounts of pertactin and other major antigens 下载免费PDF全文
Lorenzo-Pajuelo B Villanueva JL Rodríguez-Cuesta J Vergara-Irigaray N Bernabeu-Wittel M Garcia-Curiel A Martínez de Tejada G 《Journal of clinical microbiology》2002,40(9):3146-3154
Although Bordetella bronchiseptica can infect and colonize immunocompromised humans, its role as a primary pathogen in pneumonia and other respiratory processes affecting those patients remains controversial. A case of cavitary pneumonia caused by B. bronchiseptica in an AIDS patient is presented, and the basis of the seemingly enhanced pathogenic potential of this isolate (designated 814) is investigated. B. bronchiseptica was the only microorganism recovered from sputum, bronchoalveolar lavage fluid, and samples taken through the protected brush catheter. Unlike previous work reporting the involvement of B. bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis of in vitro antibacterial activity resulted in clearance of the infection and resolution of the pulmonary infiltrate. Although isolate 814 produced reduced amounts of several major antigens including at least one Bvg-activated factor (pertactin), the molecular basis of this deficiency was found to be BvgAS independent since the defect persisted after the bvgAS locus of isolate 814 was replaced with a wild-type bvgAS allele. Despite its prominent phenotype, isolate 814 displayed only a modest yet a significant deficiency in its ability to colonize the respiratory tracts of immunocompetent rats at an early time point. Interestingly, the antibody response elicited by isolate 814 in these animals was almost undetectable. We propose that isolate 814 may be more virulent in immunocompromised patients due, at least in part, to its innate ability to produce low amounts of immunogenic factors which may be required at only normal levels for the interaction of this pathogen with its immunocompetent natural hosts. 相似文献
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James E. Everhart Deanna Kruszon-Moran Guillermo Perez-Perez 《Clinical and Vaccine Immunology : CVI》2002,9(2):412-416
Background serological assays for Helicobacter pylori are commonly used without knowledge of reliability. This information is needed to define the ability of serological tests to determine either new cases of infection or loss of infection in longitudinal studies. We evaluated the reproducibility and the interrelationships of serological test results for H. pylori and cytotoxin-associated gene product A (CagA) enzyme-linked immunoassays within a subset of participants in a population-based study. Stored samples from 1,229 participants in the third U.S. National Health and Nutrition Examination Survey were replicate serologically tested for H. pylori and CagA. Overall disagreement was 3.4% between duplicate tests for H. pylori (or 2.3% if equivocal results were disregarded). Six percent of samples positive on the first test had an immune serum ratio at least 30% lower on repeat testing. The odds ratio for H. pylori seropositivity on retesting was 2.8 (95% confidence interval [CI] = 1.8 to 4.5) when CagA serology was positive versus when it was negative. CagA antibody was found among 47.8% of H. pylori-equivocal and 7.0% of H. pylori-negative samples. CagA-positive yet H. pylori-negative samples were more likely to occur among Mexican Americans (odds ratio, 5.2; 95% CI = 2.4 to 11.4) and non-Hispanic blacks (odds ratio, 5.5; 95% CI = 2.3 to 13.0) than among non-Hispanic whites. Relying on repeated H. pylori serological tests over time to determine infection rates may result in misinterpretation due to limits in test reproducibility. CagA testing may have a role in verifying infection. 相似文献
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Egidio L. Romano res Soyano Ramón F. Montaño Murray Ratcliffe Marilyn Olson Guillermo Suarez Nelly Martínez and Geoffrey Worstey 《Vox sanguinis》1994,66(3):194-199
Thirteen infants, 10 with A-O and 3 with B-O hemolytic disease of the newborn (ABO-HDN), were treated with synthetic A or B blood group trisaccharides (ATS, BTS) which cause dissociation of maternal antibody bound to infant red cells. The clinical outcome was compared with that of a control group of 21 infants treated with phototherapy during the preceding year. Exchange transfusion was required in 2 out of 13 infants in the experimental group and in 7 in the control group. A randomized prospective controlled study is necessary to confirm these results. 相似文献