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Srdan Verstovsek MD PhD Jean-Jacques Kiladjian MD PhD Alessandro M. Vannucchi MD Ruben A. Mesa MD FACP Peg Squier MD PhD J. E. Hamer-Maansson MSPH Claire Harrison MD 《Cancer》2023,129(11):1681-1690
Background
In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).Methods
This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.Results
The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.Conclusions
These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.Plain Language Summary
- Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
- Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
- Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
- Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.
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Magdalena Cortes Alessandro Lambiase Marta Sacchetti Silvia Aronni Stefano Bonini 陈旭 《美国医学会眼科杂志(中文版)》2006,18(1):30-32
泪管-耳-牙-指(趾)(LADD)综合征是一种具有多种表现的常染色体显性遗传疾病。最初在1967年由Levy报道。1例双侧泪液系统缺失、杯状耳、干嘴,以及牙、手臂和指(趾)异常的单发病例。之后一些新发现的临床表现,如肾脏异常、唾液腺缺乏、先天性髋脱位、先天性裂孔疝和横膈疝、感觉性耳聋和传导性耳聋、牙发育不全、四肢异常、口腔干燥和眼干都被报道与此综合征有关。 相似文献
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Adriana B Campaner Alessandro Scapinelli Ruy O Machado Roberto E Dos Santos Geni W Beznos Tsutomu Aoki 《Gynecological endocrinology》2006,22(7):395-398
We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries. 相似文献
5.
Monica Conciatori Christopher J Stodgell Susan L Hyman Melanie O'Bara Roberto Militerni Carmela Bravaccio Simona Trillo Francesco Montecchi Cindy Schneider Raun Melmed Maurizio Elia Lori Crawford Sarah J Spence Lucianna Muscarella Vito Guarnieri Leonardo D'Agruma Alessandro Quattrone Leopoldo Zelante Daniel Rabinowitz Tiziana Pascucci Stefano Puglisi-Allegra Karl-Ludvig Reichelt Patricia M Rodier Antonio M Persico 《Neuropsychopharmacology》2004,55(4):413-419
BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference. 相似文献
6.
Giuseppina Di Stefano Luigi Fiume Michele Baglioni Corrado Busi Pasquale Chieco Felix Kratz Alessandro Mattioli 《European journal of pharmaceutical sciences》2007,30(2):136-142
Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma. 相似文献
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Ennio Toscano Alessandro Simonati Yasuhiro Indo Generoso Andria 《Annals of neurology》2003,53(3):418-419
10.
Andrea Gallamini Alberto Biggi Adriana Fruttero Francesco Pugno Giobatta Cavallero Patrizia Pregno Mariella Grasso Chiara Farinelli Alessandro Leone Eugenio Gallo 《European journal of nuclear medicine and molecular imaging》1997,24(12):1499-1506
The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin’s
lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the
67Ga uptake by the tumour, and to establish the contribution of 67Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over
a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic 67Ga score at diagnosis. In addition to 67Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host.
Univariate and multivariate analyses were used. 67Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography
scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with
a dismal prognosis: with a mean follow-up of 47 months (range: 1–146 months) the median survival time was 28 months in patients
with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27.4%±14.9% (mean ±SD) in the former and 8.9%±7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis.
It is concluded that 67Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other
prognostic variables.
Received 1 May and in revised form 6 August 1997 相似文献