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Articoli di riviste sul tema "355.009 44":
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Akpek, Görgün, Marianna L. Zahurak, Steven Piantadosi, Jeffrey Margolis, Jon Doherty, Robert Davidson e Georgia B. Vogelsang. "Development of a prognostic model for grading chronic graft-versus-host disease". Blood 97, n. 5 (1 marzo 2001): 1219–26. http://dx.doi.org/10.1182/blood.v97.5.1219.
Abstract (sommario):
The disease-specific survival (DSS) of 151 patients with chronic graft-versus-host disease (cGVHD) was studied in an attempt to stratify patients into risk groups and to form a basis for a new grading of cGVHD. The data included the outcome and 23 variables at the diagnosis of cGVHD and at the primary treatment failure (PTF). Eighty-nine patients (58%) failed primary therapy for cGVHD. Nonrelapse mortality was 44% after a median follow-up of 7.8 years. The probability of DSS at 10 years after diagnosis of cGVHD (DSS1) and after PTF (DSS2) was 51% (95% confidence interval [CI] = 39%, 60%) and 38% (95% CI = 28%, 49%), respectively. According to multivariate analysis, extensive skin involvement (ESI) more than 50% of body surface area; hazard ratio (HR) of 7.0 (95% CI = 3.6-13.4), thrombocytopenia (TP) (< 100 000/μL; HR, 3.6; 95% CI = 1.9-6.8), and progressive-type onset (PTO) (HR, 1.7; 95% CI = 0.9-3.0) significantly influenced DSS1. These 3 factors and Karnofsky Performance Score of less than 50% at PTF were significant predictors for DSS2. The DSS1 at 10 years for patients with prognostic factor score (PFS) at diagnosis of 0 (none), less than 2 (ESI only or TP and/or PTO), 2 to 3.5 (ESI plus either TP or PTO), and more than 3.5 (all 3 factors) was 82%, 68%, 34%, and 3% (P = .05, < .001, < .001), respectively. The DSS2 at 5 years for patients with PFS at PTF of 0, 2 or less, 2 to 3.5, and more than 3.5 were 91%, 71%, 22%, and 4% (P = .2, .005, and < .001), respectively. It was concluded that these prognostic models might be useful in grouping the patients with similar outcome.
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Rugo, Hope, Mark Robson, Seock-Ah Im, Florence Dalenc, Eduardo Yañez Ruiz, Young-Hyuck Im, Sergii Kulyk et al. "Abstract GS01-05: Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study". Cancer Research 84, n. 9_Supplement (2 maggio 2024): GS01–05—GS01–05. http://dx.doi.org/10.1158/1538-7445.sabcs23-gs01-05.
Abstract (sommario):
Abstract Background: Pembrolizumab (pembro) plus chemotherapy (chemo) showed statistically significant improvements in PFS and OS vs placebo + chemo in patients (pts) with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) whose tumors expressed PD-L1 with a combined positive score (CPS) ≥10 in the phase 3 KEYNOTE-355 study. Tolerable and effective maintenance regimens after induction therapy are needed to sustain clinical benefit. The PARP inhibitor olaparib is an established maintenance therapy for multiple platinum-sensitive tumor types and prior data suggest that PARP inhibitors combined with PD-1/PD-L1 inhibitors could provide an improved therapeutic effect. KEYLYNK-009 (NCT04191135) is a randomized open-label phase 2 study to evaluate the efficacy and safety of maintenance pembro + olaparib vs pembro + chemo in pts with locally recurrent inoperable or metastatic TNBC who had clinical benefit from induction with 1L pembro + platinum-based chemo. Methods: Eligible pts with measurable, locally recurrent inoperable or metastatic TNBC that had not been previously treated with chemo in the metastatic setting received induction therapy for up to 6 cycles of pembro 200 mg + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 and 8) every 3 wk (Q3W). Pts with complete response (CR), partial response (PR), or stable disease (SD) after 4-6 treatment cycles were randomized 1:1 to receive pembro 200 mg Q3W + olaparib 300 mg twice daily or pembro + chemo (continued induction regimen). Olaparib or chemo was continued until progression or unacceptable toxicity; pembro was continued for up to 35 cycles (including induction treatment), progression, or unacceptable toxicity. Pts were stratified by induction response (CR or PR vs SD, by RECIST v1.1), tumor PD-L1 status (CPS ≥1 vs CPS < 1), and tumor genomic status (tBRCAm vs tBRCAwt). Dual primary endpoints were PFS per RECIST v1.1 by BICR and OS from randomization in all pts. Secondary endpoints included PFS and OS from randomization in pts with PD-L1 CPS ≥10 tumors and in pts with tBRCAm, and safety. Results: Of the 460 pts who received induction therapy, 271 were randomly assigned to pembro + olaparib (n=135) or pembro + chemo (n=136). At the Dec 15, 2022 data cutoff, median follow-up was 17.2 mo. Maintenance pembro + olaparib did not significantly improve PFS or OS vs pembro + chemo after induction therapy (Table). Median PFS was longer with pembro + olaparib vs pembro + chemo in pts with tBRCAm, but not in pts with PD-L1 CPS ≥10 tumors; a similar trend was observed for OS (Table). In 268 treated pts, treatment-related AEs (TRAEs) occurred in 114 of 135 pts (84.4%) for pembro + olaparib and in 128 of 133 pts (96.2%) for pembro + chemo. Grade ≥3 TRAEs occurred in 44 pts (32.6%) for pembro + olaparib (0 deaths) and in 91 pts (68.4%) for pembro + chemo (2 [1.5%] deaths), with 12 (8.9%) vs 26 (19.5%) discontinuations for TRAEs, respectively. Conclusions: The primary endpoints of PFS and OS were not met in an unselected population of pts with advanced TNBC. However, directionally favorable improvements in PFS and OS were observed in pts with tBRCAm with pembro + olaparib vs pembro + chemo, representing a potential maintenance strategy. Further data are required to confirm this effect. No new safety signals were observed, and there were fewer TRAEs in the pembro + olaparib group vs the pembro + chemo group. PFS and OS were evaluated from the time of randomization. *Based on stratified Cox regression model with Efron’s method of tie-handling with treatment as a covariate. NR = not reached. Citation Format: Hope Rugo, Mark Robson, Seock-Ah Im, Florence Dalenc, Eduardo Yañez Ruiz, Young-Hyuck Im, Sergii Kulyk, Oleksandr Dudnichenko, Néstor Llinás-Quintero, Shigehira Saji, Yasuo Miyoshi, Nadia Harbeck, Li Fan, Jaime Mejia, Vassiliki Karantza, David Cescon. Pembrolizumab + Olaparib vs Pembrolizumab + Chemotherapy After Induction With Pembrolizumab + Chemotherapy for Locally Recurrent Inoperable or Metastatic TNBC: Randomized Open-Label Phase 2 KEYLYNK-009 Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-05.
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Soverini, Simona, Sabrina Colarossi, Alessandra Gnani, Gianantonio Rosti, Fausto Castagnetti, Angela Poerio, Ilaria Iacobucci et al. "Frequency, Distribution and Prognostic Value of ABL Kinase Domain (KD) Mutations in Different Subsets of Philadelphia-Positive (Ph+) Patients (Pts) Resistant to Imatinib (IM) by the Gimema Working Party on CML." Blood 106, n. 11 (16 novembre 2005): 435. http://dx.doi.org/10.1182/blood.v106.11.435.435.
Abstract (sommario):
Abstract Using denaturing-high performance liquid chromatography and sequencing, we screened for ABL KD mutations 319 IM-resistant Ph+ pts. Median time between diagnosis and IM start at 400–600 mg/d was 40 (0–160) months. Median duration of IM was 27 (9–62) months. Evaluable pts were 256/319 (80%). At the time of analysis, 178/256 (70%) pts were in chronic phase (CP)(36 previously untreated, 142 post-IFN failure), 16 (6%) pts were in accelerated phase (AP), 26 (10%) pts were in myeloid blast crisis (myBC), 36 (14%) were in lymphoid blast crisis (lyBC) or had Ph+ acute lymphoblastic leukemia (ALL). One hundred and forty-two pts had primary resistance to IM, 114 had acquired resistance. Ninety-eight mutations were found in 91/256 (36%) pts. In 6 pts (2 Ph+ ALL, 2myBC, 1 lyBC, 1 CP post-IFN failure) multiple mutations simultaneously occurred. Mutations mapped to 15 codons, the most frequent ones being E255K/V (15 pts), Y253F/H (12 pts), T315I (10 pts), M351T (10 pts), F359V/I (10 pts), M244V (9 pts), G250E (8 pts). Three novel amino acid substitutions (F311I; E355D; F359I) and a novel mutated codon (P296H) were detected; biochemical/structural characterization will be presented. Mutations were found in 36/178 (26%) CP pts (4/36 (11%) previously untreated, 32/142 (22%) post-IFN failure), 7/16 (44%) AP pts, 19/26 (73%) myBC pts and 29/36 (81%) lyBC/Ph+ ALL pts (CP vs. AP, p=.04; AP vs. BC, p=.01; CP vs. BC, p<.001). Mutations were associated in 41/142 (29%) pts with primary resistance (4/8 hematologic and 37/134 cytogenetic) and in 50/114 (44%) pts with acquired resistance (10/50 pts who lost CCgR, 16/32 pts who lost HR, 24/32 pts who progressed to AP/BC)(primary vs. acquired, p=.009). Thirty-nine out of 49 pts with P-loop or T315I mutations had already progressed to AP/BC at the time of mutation detection; 4 additional pts subsequently progressed. In contrast, only 17 of the 42 remaining pts with mutations had progressed or subsequently progressed (p<.001). In a subset of 93 IM-resistant CP pts who were homogeneously treated in the CML/002/STI571 trial, with a follow-up ranging between 10 and 51 months, presence of a mutation was significantly associated with greater likelihood of progression (Log-Rank p<.001) and shorter survival (Log-Rank p=.005). Pts carrying P-loop or T315I mutations showed a particularly poor outcome both in terms of time to progression (Log-Rank p=.003) and in terms of survival (Log-Rank p=.02). We conclude that: a) there is a significantly higher probability of mutations according to disease phase (Ph+ ALL and BC>AP>CP); b) there is a significantly higher probability of mutations in pts with acquired resistance vs. pts with primary resistance; c) mutations, and in particular those affecting P-loop or codon 315, are associated with a worse outcome. Supported by AIL, AIRC, Fondazione del Monte di Bologna e Ravenna.
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Rogers, Jonathan, Camarie Welgemoed e Dorothy Gujral. "Does body mass index or subcutaneous adipose tissue thickness affect interfraction prostate motion in patients receiving radical prostate radiotherapy?" Journal of Radiotherapy in Practice 15, n. 4 (9 settembre 2016): 334–40. http://dx.doi.org/10.1017/s1460396916000364.
Abstract (sommario):
AbstractAimIt is unclear whether body mass index (BMI) is a useful measurement for examining prostate motion. Patient’s subcutaneous adipose tissue thickness (SAT) and weight has been shown to correlate with prostate shifts in the left/right direction. We sought to analyse the relationship between BMI and interfraction prostate movement in order to determine planning target volume (PTV) margins based on patient BMI.Materials and methodsIn all, 38 prostate cancer patients with three implanted gold fiducial markers in their prostate were recruited. Height, mass and SAT were measured, and the extent of interfraction prostate movement in the left/right, superior/inferior and anterior/posterior directions was recorded during each daily fiducial marker-based image-guided radiotherapy treatment. Mean corrective shift in each direction for each patient, along with BMI values, were calculated.ResultsThe median BMI value was 28·4 kg/m2 (range 21·4–44·7). Pearson’s product-moment correlation analysis showed no significant relationship between BMI, mass or SAT and the extent of prostate movement in any direction. Linear regression analysis also showed no relationship between any of the patient variables and the extent of prostate movement in any direction (BMI: R2=0·006 (ρ=0·65), 0·002 (ρ=0·80) and 0·001 (ρ=0·86); mass: R2=0·001 (ρ=0·87), 0·010 (ρ=0·54) and 0·000 (ρ=0·99); SAT: R2=0·012 (ρ=0·51), 0·013 (ρ=0·50) and 0·047 (ρ=0·19) for shifts in the X, Y and Z axis, respectively). Patients were grouped according to BMI, as BMI<30 (n=25, 65·8%) and BMI≥30 (n=13, 34·2%). A two-tailed t-test showed no significant difference between the mean prostate shifts for the two groups in any direction (ρ=0·320, 0·839 and 0·325 for shifts in the X, Y and Z axis, respectively).FindingsBMI is not a useful parameter for determining individualised PTV margins. Gold fiducial marker insertion should be used as standard to improve treatment accuracy.
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Zucali, Paolo A., Matteo Simonelli, Fabio De Vincenzo, Armando Santoro, Antonio Lambiase e Claudio Bordignon. "Changes in shedding of soluble tumor necrosis factor receptors (sR1/R2) and in dynamic MRI as early predictors of outcome with NGR-hTNF." Journal of Clinical Oncology 31, n. 15_suppl (20 maggio 2013): e22145-e22145. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e22145.
Abstract (sommario):
e22145 Background: Dose-response curve of NGR-hTNF, a selective antivascular agent, is typically biphasic with activity shown either at low dose (LD) or high dose (HD). Receptor shedding may block drug activity. Vascular effects at LD are characterized by early vessel stabilization and late vessel damage, while at HD by rapid vessel disruption. Methods: 60 pts (median age: 61; M/F: 44/16; PS 0/≥1: 25/35; median prior lines: 3) received in 2 ph I trials NGR-hTNF at LD (0.2-1.6 µg/m2; n=14) or HD (60-325 µg/m2; n=46) every 3 weeks. We tested the impact of early changes (post 1st dose) in baseline-normalized plasma receptor levels (n=60) and in DCE-MRI-assessed Ktrans (n=49) on treatment effect, including disease control (DC, rate of pts progression free at 6 weeks by RECIST criteria) and progression free survival (PFS). Results: Baseline receptor levels were not related to outcome. Post-dosing levels of sR1 (median, 4.6 ng/mL; interquartile range, 2.8-5.7) and sR2 (8.6; 4.5-10.7) increased with dose (p<.0001 for both), with median values of sR1 (0.3) and sR2 (0.5) at LD being significantly lower than those of sR1 (4.9) and sR2 (9.6) at HD (p<.0001 for both). Using as cutoff the 1st quartile, low sR1 levels (≤2.8 ng/mL) correlated with improved DC (OR=4.9; p=0.01) and PFS (HR=0.30; p=.003). In low vs high groups, median DC duration was 7.4 vs 2.9 months and 6-month PFS was 29% vs 0%, respectively. By adjusting for baseline covariates (age, sex, PS and prior lines), low sR1 levels remained independently associated with better DC (p=.02) and PFS (p=.008). Similar effects were noted for sR2. Levels of sR1 (r=-0.35; p=.01) and sR2 (r=-0.27; p=.07) inversely correlated with early fractional decreases in Ktrans, which resulted in median values unchanged after LD (4%; p=.73) and reduced after HD (-32%; p=.009). However, Ktrans significantly declined over time after both LD (-24%; p=.04) and HD (-44%; p=.001). Early changes in Ktrans did not relate with DC as defined by RECIST, but smaller decreases in Ktrans were associated with longer PFS (HR=0.56; p=.04). Conclusions: NGR-hTNF at LD is associated with better outcome than at HD likely due to early effects that involve minimal receptor shedding and vessel stabilization. Clinical trial information: NCT00878111-NCT00914628.
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Wang, Jiali, Lijun Zhao, Junlin Zhang, Yiting Wang, Yucheng Wu, Qianqian Han, Tingli Wang et al. "CLINICOPATHOLOGIC FEATURES AND PROGNOSIS OF TYPE 2 DIABETES MELLITUS AND DIABETIC NEPHROPATHY IN DIFFERENT AGE GROUPS: MORE ATTENTION TO YOUNGER PATIENTS". Endocrine Practice 26, n. 1 (gennaio 2020): 51–57. http://dx.doi.org/10.4158/ep-2019-0238.
Abstract (sommario):
Objective: Our study sought to investigate the clinicopathologic features and renal prognosis of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different age groups. Methods: A total of 315 patients with T2DM and biopsy-proven DN were enrolled and divided into three groups by age: the Youth group (≤44 years old), the Middle-aged group (45 to 59 years old), and the Elderly group (≥60 years old). Results: The Youth group, Middle-aged group, and Elderly group accounted for 19.05% (60/315), 59.37% (187/315), and 21.59% (68/315) of the patients in our study, respectively. The patients in the Youth group had a higher estimated glomerular filtration rate (calculated using the Chronic Kidney Disease–Epidemiology collaboration formula) ( P<.001), a higher incidence of diabetic retinopathy ( P = .044), and a higher incidence of being in the lower-risk chronic kidney disease heat map category ( P = .046) but lower duration of diabetes ( P = .016). Histologically, patients in the Youth group had the highest incidence of glomerular classification in class I ( P = .006) and arteriolar hyalinosis score of 0 ( P = .005). The renal survival among the three groups was comparable ( P>.05). Conclusion: This study indicated that there were different clinicopathologic features among Chinese DN patients in different age groups. Although the Youth group had a relatively lower rapid kidney disease progression rate, there were no significant differences in renal survival rate among the three groups, which calls more attention to early supervision and prevention for younger DN patients. Abbreviations: CKD = chronic kidney disease; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; G&Y&O = green and yellow and orange; IFTA = interstitial fibrosis and tubular atrophy; T2DM = type 2 diabetes mellitus
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Paiva, Bruno, Norma C. Gutierrez, Xi Chen, María-Belén Vidriales, María-Angeles Montalbán, Laura Rosiñol, Albert Oriol et al. "Biological and Clinical Significance of CD81 Expression by Clonal Plasma Cells in High-Risk Smoldering and Symptomatic Multiple Myeloma (MM) Patients",. Blood 118, n. 21 (18 novembre 2011): 3936. http://dx.doi.org/10.1182/blood.v118.21.3936.3936.
Abstract (sommario):
Abstract Abstract 3936 The presence of CD19 in myelomatous plasma cells (MM-PC) correlates with adverse prognosis in MM. Although CD19 expression is up-regulated by CD81, this marker has been poorly investigated and its prognostic value in myeloma remains unknown. Herein, we assessed the frequency and the prognostic value of the immunophenotypic detection of CD81 surface expression in MM-PC of high-risk smoldering (SMM) and symptomatic MM patients at diagnosis and its role as a potential therapeutic target. The study included 230 elderly MM patients treated according to the Spanish GEM05>65y trial, and a validation set based on 325 transplant candidates MM patients enrolled in the GEM05<65y trial was used. In addition we analyzed a total of 56 high-risk SMM patients. The median follow-up was 32 and 22 months for the MM and SMM, respectively. Expression of CD81 on MM-PC was assessed by multiparameter flow cytometry (MFC). FISH was performed at baseline in immunomagnetic-enriched PCs from 211 of the 230 elderly MM patients, and in a subset of these patients (N=23) mRNA gene expression profiling (GEP) was also performed. MFC immunophenotyping showed the presence of CD81+ MM-PC in 20 of 56 (36%) SMM, and 90 of 230 (39%) MM patients. CD81+ SMM cases had a shorter TTP to symptomatic disease than CD81− patients (NR vs 37 months, P =.02). Similarly, CD81+symptomatic MM patients showed shorter PFS (3y: 29% vs 48%, P <.001) and OS (3y: 64% vs 76%, P =.008) rates compared to CD81− cases. Multivariate analysis including other baseline variables showed that the best combination of independent predictive parameters for PFS were: CD81+ expression on MM-PC (HR=1.8; P =.004), high-risk cytogenetics (HR=1.8; P =.02) and percentage of MM-PC in S-phase (>2%; HR=1.7; P =.02); in turn for OS, CD81+ expression (HR=2.2; P =.005), high-risk cytogenetics (HR=2.2; P =.006) and age (≥75 years; HR=1.8; P =.03) were selected. To validate the adverse impact of CD81+ expression, we explored whether this new marker would retain its prognostic value in a series of 325 transplant candidates, symptomatic MM patients. CD81+ cases (138 out of 325, 42%) showed shorter PFS (3y: 44% vs 62%, P <.001) and OS (3y: 74% vs 89%, P =.004) rates as compared to CD81− cases. The prognostic influence of CD81 expression prompted us to investigate its potential role as a therapeutic target in MM cell lines. 5 out of the 13 cell lines analyzed were homogeneously positive for CD81 (RPMI-8226, RPMI-LR5, NCI-H929, OPM-2, JJN3) while the others exhibited no expression; these results were further validated by western blotting. We then tested the effect of two different anti-CD81 antibodies on cell proliferation on 2 CD81+ cell lines (RPMI-8226 and JJN3) as well as in 1 CD81− (MM1S) MM cell line. Interestingly, the two antibodies tested decreased cell proliferation (around 30%, P ≤.005) in the two CD81+ cell lines, whereas no differences were found for the CD81− MM1S cell line. To assess whether anti-CD81 antibodies facilitate immune effector cell function, we performed in vitro ADCC. However, no effect was noted in the CD81+ RPMI-8226 cell line, using either PBMCs or the macrophage cell line RAW264.7, and at different cell ratios. Similar results were also found upon using CDC assay in CD81+ RPMI-8226 and JJN3 cell lines. Finally, we explored in a subgroup of MM patients (n=23) in which information was available, the relationship between positivity for CD81 by MFC and its genomic expression. The expression level of CD81 mRNA was significantly decreased in CD81− MM cases (P <.001) vs. both healthy adults and CD81+ patients (P <.001), with no significant differences between these two latter subgroups. Moreover, we found a highly significant correlation between the expression of CD81 mRNA by GEP and the percentage of CD81+ MM-PC by MFC (r=.812; P <.001). We further investigated by GEP, differences in other genes involved in the CD81 signaling pathway, and CD81+MM patients showed significantly higher levels of CD79A (P =.03) and SYK (P =.02) mRNA than CD81−cases. In summary, our findings show the existence of a phenotypic-genomic correlation of CD81 expression in patients with myeloma. Expression of CD81 in MM-PC is an independent prognostic factor for patients with symptomatic MM and a marker for risk of progression in SMM. Blockage of CD81 with anti-CD81 antibodies does not show significant anti-myeloma activity; therefore, the precise mechanism of CD81 activation of MM-PC deserves further investigations. Disclosures: Paiva: Celgene: Honoraria; Janssen: Honoraria. Rosiñol:Janssen: Honoraria; Celgene: Honoraria. Mateos:Janssen: Honoraria; Celgene: Honoraria. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. Blade:Janssen: Honoraria; Celgene: Honoraria. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria.
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Awada, Hassan, Cassandra M. Kerr, Vera Adema, Carmelo Gurnari, Simona Pagliuca, Heesun J. Rogers, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski e Valeria Visconte. "The Clonal Trajectories of SF3B1 Mutations in Myeloid Neoplasia". Blood 136, Supplement 1 (5 novembre 2020): 8. http://dx.doi.org/10.1182/blood-2020-139528.
Abstract (sommario):
Molecular lesions have diagnostic and prognostic impacts in myeloid neoplasia (MN). The beau idéal is the presence of SF3B1MT in MDS with ringed sideroblasts. Although most of these patients have a classic phenotype, little is known about the factors diverting it during the clonal evolution. Clinical trajectories of patients with SF3B1MT might depend on clonal hierarchy, dynamics and subclonal diversity in relation to other lesions. Herein, we studied the molecular architecture of patients with SF3B1MT to determine whether clonality and rank might infer distinct MDS features. We collected molecular and clinical information of 3561 patients with MN from Cleveland Clinic and publicly shared data. Results of targeted deep sequencing of 176 MDS/ AML genes were included. We applied an in-house variant allele frequency (VAF) based bioanalytic method to resolve clonal hierarchy. VAF (adjusted for copy number and zygosity) was used to classify the mutations into dominant (if a cutoff of at least 5% difference between VAFs existed), secondary (any subsequent subclonal hit) and codominant hits (<5% difference of VAFs between 2 hits). SF3B1 MT were detected in 9% of patients (n=335): 140 were SF3B1DOM (42%), 121 were SF3B1SEC (36%) and 74 were codominant (SF3B1COD, 22%). Comparison of SF3B1MT VAFs among the 3 groups showed no significant difference (40 vs 39 vs 44%, P= .6). Due to lack of distinct partition, we delved into the implications of SF3B1COD on mutational stability, disease phenotypes, molecular associations and overall survival (OS) as compared to the other 2 configurations. Serially-collected samples (n=21) showed clear scenarios of dominant clones remaining stable or switching to secondary due to impending acquisition of other hits or secondary clones remaining as such but denoted an ambivalent framework of codominant clones with "sweeping" features. Cases with SF3B1COD had a trend of OS similar to that of SF3B1SEC (median OS: 18 vs 15.9 mo.) and as such a poorer outcome compared to that of SF3B1DOM (39.8 mo.; P= .02). Moreover, the mutational profile of SF3B1CODvsSF3B1DOM was partially similar to that of SF3B1SECvs.SF3B1DOM with significantly higher odd ratios for DNMT3A (P< .0001), ASXL1, FLT3, RUNX1, TET2 (P≤ .05 for each). No variant morphologic features were observed when comparing SF3B1COD to the other 2 groups. By virtue, we strictly compared only cases with SF3B1DOM and SF3B1SEC, further supported by our single cell analysis(n=5), to showan unambiguous distinction between these two statii. Mutational burden analysis revealed that SF3B1DOM patients had a fewer number of mutations than those with SF3B1SEC (median 1.0 vs 2.6). SF3B1DOM was mostly detected in patients with a normocellular bone marrow as compared to SF3B1SEC (46 vs 29%, P= .02) and had a lower proportion of multidysplastic myeloid cells (29 vs 53%, P= .01). On the other side, SF3B1SEC were often present in the context of bilineage dysplasia (47vs. 26%, P= .02). Focused morphologic analysis revealed that SF3B1DOM cases were significantly associated with a higher RS% (median 37 vs 3%, P= .002; frequency of RS ≥15%: 77 vs 44%, P= .003) with higher VAF% significantly correlating with higher RS%. Patients with SF3B1SEC had shorter OS than those with SF3B1DOM (15.9 vs 39.7 mo., P< .0001). Even by dichotomizing according to VAF, the median OS of cases with VAF>40% was significantly shorter than those with VAF<20% (14.4 vs 33.9 mo.; P= .001) and between 20% and 40% (39.3 mo.). When the VAF of SF3B1SEC was >40%, the OS was shortened compared to SF3B1DOM (31 vs 11.6 mo., P= .001) and similarly when it laid between 20% and 40% (49.7 vs 25.6 mo., P= .01) suggesting a strong impact of associated hits. In SF3B1SEC, univariate analyses showed significantly higher odds of hits in RUNX1 (43 vs 19%, P< .0001), TET2 (29 vs 11%, P= .0005), FLT3 (22 vs 11%, P= .02), DNMT3A (20 vs 7%, P= .004), ASXL1 (16 vs 5%, P= .06), BCOR/L1 (17 vs 5%, P= .005), IDH1/2 (11 vs 2%, P= .008), CBL (8 vs 1%, P= .009) and CEBPA (7 vs 2%, P= .04) compared to SF3B1DOM. Interestingly, cases with co-existing TET2 mutations had a marked decrease in OS in SF3B1SECvsSF3B1DOM(10.1 vs 96.1 mo., P= .02) suggesting that the mutational ranking in a disease triggered by SF3B1MT can be skewed by stronger hits. In sum, our study suggests that molecular ranking in the context of SF3B1 clonal configuration is a key factor diverting the clinical and phenotypic trajectories of patients with MN and SF3B1MT. Disclosures Carraway: BMS: Consultancy, Other: Research support, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Takeda: Other: Independent Advisory Committe (IRC); ASTEX: Other: Independent Advisory Committe (IRC); Abbvie: Other: Independent Advisory Committe (IRC); Novartis: Consultancy, Speakers Bureau. Sekeres:Pfizer: Consultancy; BMS: Consultancy; Takeda/Millenium: Consultancy. Maciejewski:Alexion, BMS: Speakers Bureau; Novartis, Roche: Consultancy, Honoraria.
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Heikura, Ida A., Louise M. Burke, Dan Bergland, Arja L. T. Uusitalo, Antti A. Mero e Trent Stellingwerff. "Impact of Energy Availability, Health, and Sex on Hemoglobin-Mass Responses Following Live-High–Train-High Altitude Training in Elite Female and Male Distance Athletes". International Journal of Sports Physiology and Performance 13, n. 8 (1 settembre 2018): 1090–96. http://dx.doi.org/10.1123/ijspp.2017-0547.
Abstract (sommario):
Purpose: The authors investigated the effects of sex, energy availability (EA), and health status on the change in hemoglobin mass (ΔHbmass) in elite endurance athletes over ∼3–4 wk of live-high–train-high altitude training in Flagstaff, AZ (2135 m; n = 27 women; n = 21 men; 27% 2016 Olympians). Methods: Precamp and postcamp Hbmass (optimized carbon monoxide rebreathing method) and iron status were measured, EA was estimated via food and training logs, and a Low Energy Availability in Females Questionnaire (LEAFQ) and a general injury/illness questionnaire were completed. Hypoxic exposure (h) was calculated with low (<500 h), moderate (500–600 h), and high (>600 h) groupings. Results: Absolute and relative percentage ΔHbmass was significantly greater in women (6.2% [4.0%], P < .001) than men (3.2% [3.3%], P = .008). %ΔHbmass showed a dose–response with hypoxic exposure (3.1% [3.8%] vs 4.9% [3.8%] vs 6.8% [3.7%], P = .013). Hbmasspre was significantly higher in eumenorrheic vs amenorrheic women (12.2 [1.0] vs 11.3 [0.5] g/kg, P = .004). Although statistically underpowered, %ΔHbmass was significantly less in sick (n = 4, −0.5% [0.4%]) vs healthy (n = 44, 5.4% [3.8%], P < .001) athletes. There were no significant correlations between self-reported iron intake, sex hormones, or EA on Hbmass outcomes. However, there was a trend for a negative correlation between LEAFQ score and %ΔHbmass (r = −.353, P = .07). Conclusions: The findings confirm the importance of baseline Hbmass and exposure to hypoxia on increases in Hbmass during altitude training, while emphasizing the importance of athlete health and indices of EA on an optimal baseline Hbmass and hematological response to hypoxia.
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Fonseca, Rafael, Emily Blood, Montserrat Rue, David Harrington, Martin M. Oken, Robert A. Kyle, Gordon W. Dewald et al. "Clinical and biologic implications of recurrent genomic aberrations in myeloma". Blood 101, n. 11 (1 giugno 2003): 4569–75. http://dx.doi.org/10.1182/blood-2002-10-3017.
Abstract (sommario):
Abstract Nonrandom recurrent chromosomal abnormalities are ubiquitous in multiple myeloma (MM) and include, among others, translocations of the immunoglobulin heavy chain locus (IgH). IgH translocations in MM result in the up-regulation of oncogenes, and include more commonly t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23). Based on the recurrent nature of these translocations and their finding since the early stages of the plasma cell (PC) disorders, we hypothesized that they would confer biologic and clinical variability. In addition, deletions of 13q14 and 17p13 have also been associated with a shortened survival. We used cytoplasmic Ig—enhanced interphase fluorescent in situ hybridization to detect deletions (13q14 and 17p13.1), and translocations involving IgH in 351 patients treated with conventional chemotherapy entered into the Eastern Cooperative Oncology Group clinical trial E9486/9487. Translocations were frequently unbalanced with loss of one of the derivative chromosomes. The presence of t(4; 14)(p16;q32) (n = 42; 26 vs 45 months, P < .001), t(14;16)(q32;q23) (n = 15; 16 vs 41 months, P = .003), – 17p13 (n = 37; 23 vs 44 months, P = .005), and – 13q14 (n = 176; 35 vs 51 months, P = .028) were associated with shorter survival. A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and – 17p13), intermediate prognosis (– 13q14), and good prognosis group (all others), with median survivals of 24.7, 42.3, and 50.5 months, respectively (P < .001). This molecular cytogenetic classification identifies patients into poor, intermediate, and good risk categories. More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations.
Libri sul tema "355.009 44":
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Tardif, Geneviève. Le petit Druide des synonymes et des antonymes: Dictionnaire : 305 000 synonymes, 44 000 antonymes. 2a ed. Montréal: Druide, 2011.
Capitoli di libri sul tema "355.009 44":
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Franklin, Matheus Lucas Meireles, Ingrid Moreira Melo, Catharinna Aiko Odagiri de Moraes, Naiana Palheta Moraes, Fábio Venâncio de Oliveira, Renato Garcia Lisboa Borges, Julius Caesar Mende Soares Monteiro e Simone Regina Souza da Silva Conde. "Avaliação epidemiológica e clínica de pacientes pós infecção pelo Sars-Cov-2 na região metropolitana de Belém". In Impactos na saúde da Covid-19 em uma população da Amazônia. Seven Editora, 2023. http://dx.doi.org/10.56238/impcsaudcovid19amazo-001.
Abstract (sommario):
A princípio, a COVID-19 foi descrita como uma doença respiratória de vias aéreas superiores ocasionada pelo SARS-CoV-2, que poderia estabelecer uma pneumonia viral. No entanto, conforme a pandemia evoluía, verificou-se o caráter sistêmico do agravo, durante e após a infecção. Estimava-se que 81% das pessoas iriam desenvolver a forma leve da doença, sem comprometimento de outros órgãos; porém, entre os 19% que desenvolveriam a forma grave, 5% poderiam ter uma apresentação crítica, culminando em choque e disfunção de múltiplos órgãos. Considerando a estatística de casos no Estado do Pará, a pandemia apresentou um acumulado de 847.305 casos confirmados, 18.897 óbitos e letalidade em 2,23% até novembro/2022. Desta forma, o presente trabalho tem por objetivo descrever características clínicas e epidemiológicos de indivíduos residentes na Região Metropolitana de Belém com síndrome pós COVID-19. Realizou-se um estudo exploratório, observacional, transversal e quantitativo, a partir de dados dos participantes atendidos ambulatorialmente nos serviços participantes. Projeto aprovado pelo Comitê de Ética em Pesquisa. Como resultados, do total de 62 indivíduos avaliados, maioria do sexo feminino (77,42%), com idade de 55±11 anos, com relatos de infecção única pelo SARS-CoV-2 (61,40%), diagnosticados através de RT-PCR por swab nasal (72,58% na primeira infecção e 72,72% em reinfecções), com duas doses da vacina (55/62, 88,7%). Dentre as comorbidades relatadas, as mais frequentes foram: hipertensão arterial (49,02%), dislipidemia (27,45%), diabetes (21,57%) e sobrepeso/obesidade (13,73%). Relataram sintomas de fadiga/astenia (53,23%), alteração de memória/amnésia (33,87%), dispneia (32,26%), ansiedade (29,03%), alopecia (17,74%) e artralgias (16,13%). Ao exame físico, 24,19% apresentaram alterações pressóricas (>140/90mmHg), alteração sistólica ou diastólica isoladamente (25,81%); frequência cardíaca basal teve variação de 44 a 110 bpm. A maioria (75%) apresentou IMC compatível com sobrepeso/obesidade e circunferência abdominal aumentada (64,5%). Apenas dois indivíduos apresentaram saturação de oxigênio (SpO2%) abaixo de 95. Apenas 35/62 (56,4%) puderam ser avaliados com exames bioquímicos, hematológicos, eletrocardiográficos e radiológicos, e a maioria não apresentou alterações significativas nesses. Os dados mensurados a partir do presente estudo se alinham com outros levantamentos sobre síndrome pós-COVID-19, pois apesar de uma minoria com alterações laboratoriais/radiológicas, a maioria apresentou sinais/sintomas de alterações mentais e comorbidades, que necessitam de um acompanhamento clínico minucioso e seriado.
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"Hopi Religion The author gratefully acknowledges the assistance of Alice Schlegel in the preparation of this chapter. Alice Schlegel, a professor of anthropology at the University of Arizona, has maintained contacts among the Hopi for over twenty years and has written extensively on gender aspects of Hopi society and religion as well as comparative studies of adolescence. The sources for the data on sex/gender aspects of Hopi culture and religion are primarily the works of Alice Schlegel; the interpretations are predominantly due to her insights; and quotations not otherwise noted are from her writings: “The Adolescent Socialization of the Hopi Girl ,” Ethnology 12 (1973): 440–462; “Hopi Joking and Castration Threats,” Linguistics and Anthropology: In Honor of C.F. Voegelin , ed. M. D. Kinkade , H. Hale , & O. Werner ( Lisse, Netherlands : Peter de Ridder Press, 1975): 521–529; “Male and Female in Hopi Thought and Action,” in Sexual Stratification: A Cross-Cultural View , ed. A. Schlegel ( New York : Columbia University Press, 1977): 245–269; “Sexual Antagonism Among the Sexually Egalitarian Hopi ,” Ethos 7 (1979): 124–141; “Hopi Gender Ideology of Female Superiority ,” Quarterly Journal of Ideology 8/4 (1984): 44–52; “Fathers, Daughters, and Kachina Dolls ,” European Review of Native American Studies 3/1 (1989): 7–10; “Gender Meanings: General and Specific,” in Beyond the Second Sex: New Directions in the Anthropology of Gender , ed. P. R. Sanday & R. G. Goodenough ( Philadelphia : University of Philadelphia Press, 1990): 23–41; and “The Two Aspects of Hopi Grandmotherhood” (manuscript). The data for most other aspects of Hopi religion are from the writings of Armin Geertz, as well as extensive personal conversations with him, for which the author is most grateful. Of Geertz’s many publications, the most relevant to this chapter are the following: “A Reed Pierced the Sky: Hopi Indian Cosmography on Third Mesa, Arizona,” Numen 31 (1984): 216–241; Hopi Indian Altar Iconography ( Leiden : E. J. Brill, 1987); with Michael Lomatuway’ma , Children of Cottonwood: Piety and Ceremonialism in Hopi Indian Puppetry ( Lincoln : University of Nebraska Press, 1987) (it is to be noted that the orthography for Hopi words are from this work); “Hopi Hermeneutics: Ritual Person Among the Hopi Indians of Arizona,” in Concepts of Person in Religion and Thought ( Berlin : de Gruyter, 1990): 309–335; and “Structural Elements in Uto-Aztecan Mythology: The Hopi Example” (manuscript). The material on ritual is in large part from Mischa Titiev , Old Oraibi: A Study of the Hopi Indians of Third Mesa ( Cambridge : Peabody Museum, 1944). For Maasaw, Ekkehart Malotki and Michael Lomatuway’ma , Maasaw: Profile of a Hopi God ( Lincoln : University of Nebraska Press, 1987) is important, as is Hamilton A. Tylor , Pueblo Gods and Myths ( Norman : University of Oklahoma Press, 1964) for deities in general. Also referred to for this chapter are Leo W. Simmons , ed., Sun Chief: The Autobiography of a Hopi Indian ( New Haven : Yale University Press, 1942) for a male perspective; and Tracy Pintchman , “Speculative Patterns in Hopi Cosmology ,” Studies in Religion 22 (1993): 351–364. The data on Papago religion is from Ruth M. Underhill , Papago Woman ( New York : Holt, Rinehart and Winston, 1979). The analysis of Zuni culture is from John W. M. Whiting et al., “The Learning of Values,” in People of Rimrock: A Study of Values in Five Cultures , ed. Evon Vogt and Ethel M. Albert ( Cambridge : Harvard University Press, 1967): 83–125/107." In Through the Earth Darkly : Female Spirituality in Comparative Perspective. Bloomsbury Academic, 1996. http://dx.doi.org/10.5040/9781350005631.ch-009.
Atti di convegni sul tema "355.009 44":
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Fulantelli, Giovanni, Lidia Scifo e Davide Taibi. "THE ECOLOGICAL SYSTEMS THEORY OF HUMAN DEVELOPMENT TO EXPLORE THE STUDENT-SOCIAL MEDIA INTERACTION." In eLSE 2021. ADL Romania, 2021. http://dx.doi.org/10.12753/2066-026x-21-019.
Abstract (sommario):
According to the Bronfenbrenner's ecological systems theory of human development ([1][2][3][4][5]), the development of each individual cannot be observed without considering its relationship with the development of other people and, above all, with the environment in which they live. The ecological orientation of Bronfenbrenner with respect to human development is therefore based on the interest in the progressive adaptation between an active organism that grows and its immediate environment: the individual-environment interaction that is determined by the relationships existing between the different environmental situations and the individuals present in that context is fundamental. Consequently, the ecological environment that is considered relevant to development processes is not limited to a single environmental situation but includes the interconnections between multiple environmental situations and the different influences of each individual. The evolution of the Internet-based technologies has brought to the development of solutions that have profoundly changed the way we live, including education. The advent of social media and social networks represents a milestone in the history of Internet, opening up to profound reflections on the "virtualization" of relationships, their growing importance in everyday life, and their role in education. Many authors argue that the Internet and the social media should no longer be considered as a tool to connect to a virtual reality that is separate from the real world, but as a place in which users live daily ([6][9][11][10]); consequently, they constitute one of the environmental situations mentioned by Bronfenbrenner. However, the risks deriving from the use of social media have been widely discusses in the literature ([7][8][12]). Adolescents are more exposed to the social media threats, since they are unable to perceive the profoundly different dynamics that govern offline and online networks. In this paper, having in mind the Bronfenbrenner's ecological systems theory of human development, we argue that the progressive adaptation of students to social media should be considered as a process of their growth and development. Furthermore, we analyze some corrections to be introduced in the educational paths of adolescents necessary to reduce the threats deriving from the use of social media and social networks in education. Reference Text and Citations [1] Bronfenbrenner, U. (1961). Toward a theoretical model for the analysis of parent-child relationships in a social context. In J. C. Glidewell (Ed.), Parental attitudes and child behavior (pp. 90-109). Springfield, IL: Charles C. Thomas. [2] Bronfenbrenner, U. (1973). Social ecology of human development. In F. Richardson (Ed.), Brain and intelligence: The ecology of child development (pp. 113-129). Hyattsville, MD: National Education Press. [3] Bronfenbrenner, U. (1974). Developmental research, public policy, and the ecology of childhood. Child Development, 45, 1-5. https://doi.org/10.2307/1127743 [4] Bronfenbrenner, U. (1994). Ecological models of human development. In T. Husen & T. N. Postlethwaite (Eds.), International encyclopedia of education (2nd ed., Vol. 3, pp. 1643-1647). Oxford, UK: Pergamon Press and Elsevier Science. [5] Bronfenbrenner, U., & Morris, P. A. (2006). The bioecological model of human development. In W. Damon (Series Ed.) & R. M. Lerner (Vol. Ed.), Handbook of child psychology: Theoretical models of human development (pp. 793-828). New York, NY: Wiley. [6] Carr, N. (2011). The Shallows: What the Internet Is Doing to Our Brains. New York: W.W. Norton & Company. [7] Livingstone, S., Haddon, L., G?rzig, A., & ?lafsson, K. (2011). Risks and safety on the internet: The perspective of European children. Full Findings. London: EU Kids Online, LSE. [Google Scholar] [8] Martin, F., Wang, C., Petty, T., Wang, W., & Wilkins, P. (2018). Middle school students' social media use. Journal of Educational Technology & Society, 21(1), 213-224. https://www.jstor.org/stable/26273881 [9] Musetti, A., Cattivelli, R., Giacobbi, M., Zuglian, P., Ceccarini, M., Capelli, F., et al. (2016). Challenges in internet addiction disorder: is a diagnosis feasible or not? Frontiers in Psychology, 7. doi: 10.3389/fpsyg.2016.00842 [10] Musetti, A., Cattivelli, R., Zuglian, P., Terrone, G., Pozzoli, S., Capelli, F., et al. (2017). Internet addiction disorder o internet related psychopathology? [Internet Addiction disorder or Internet Related Psychopathology?]. Giornale Italiano di Psicologia, 44, 359-382. doi: 10.1421/87345 [11] Taymur, I., Budak, E., Demirci, H., Akdag, H.A., Gungor, B.B., & Ozdel, K. (2016). A study of the relationship between internet addiction, psychopathology and dysfunctional beliefs. Computers in Human Behavior,61, 532-536. https://doi.org/10.1016/j.chb.2016.03.043 [12] Willoughby, M. (2018). A review of the risks associated with children and young people's social media use and the implications for social work practice. Journal of Social Work Practice,33(2), 127-140. https://doi.org/10.1080/02650533.2018.1460587