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Shiuan, Eileen, Anupama Reddy, Stephanie O. Dudzinski, Aaron R. Lim, Ayaka Sugiura, Rachel Hongo, Kirsten Young, et al. "Clinical Features and Multiplatform Molecular Analysis Assist in Understanding Patient Response to Anti-PD-1/PD-L1 in Renal Cell Carcinoma." Cancers 13, no. 6 (March 23, 2021): 1475. http://dx.doi.org/10.3390/cancers13061475.
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Predicting response to ICI therapy among patients with renal cell carcinoma (RCC) has been uniquely challenging. We analyzed patient characteristics and clinical correlates from a retrospective single-site cohort of advanced RCC patients receiving anti-PD-1/PD-L1 monotherapy (N = 97), as well as molecular parameters in a subset of patients, including multiplexed immunofluorescence (mIF), whole exome sequencing (WES), T cell receptor (TCR) sequencing, and RNA sequencing (RNA-seq). Clinical factors such as the development of immune-related adverse events (odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.05–5.91) and immunological prognostic parameters, including a higher percentage of circulating lymphocytes (23.4% vs. 17.4%, p = 0.0015) and a lower percentage of circulating neutrophils (61.8% vs. 68.5%, p = 0.0045), correlated with response. Previously identified gene expression signatures representing pathways of angiogenesis, myeloid inflammation, T effector presence, and clear cell signatures also correlated with response. High PD-L1 expression (>10% cells) as well as low TCR diversity (≤644 clonotypes) were associated with improved progression-free survival (PFS). We corroborate previously published findings and provide preliminary evidence of T cell clonality impacting the outcome of RCC patients. To further biomarker development in RCC, future studies will benefit from integrated analysis of multiple molecular platforms and prospective validation.
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Que, Xuchu, and Sharon L. Reed. "Expression and characterization of a rac family protein kinase of Entamoeba histolytica." Molecular and Biochemical Parasitology 66, no. 1 (July 1994): 111–18. http://dx.doi.org/10.1016/0166-6851(94)90041-8.
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Zhang, Ying, Jörg Ellinger, Manuel Ritter, and Ingo G. H. Schmidt-Wolf. "Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma." Cancers 12, no. 9 (September 1, 2020): 2471. http://dx.doi.org/10.3390/cancers12092471.
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There is growing interest in cytokine-induced killer (CIK) cells on the integrated therapy of patients with RCC, especially those in the late stage or refractory to conventional chemotherapy and radiotherapy. In this review, a total of 15 clinical studies including 681 patients enrolled in CIK cell immunotherapy were outlined. Three-hundred-and-eighty-two patients with RCC were treated with CIK cells alone or in combination with DC vaccination, targeted agents sunitinib or sorafenib, and the PD-1 inhibitor pembrolizumab. Significantly improved 3-year overall survival rate was reported in four trials, whereas remarkably longer median progression-free survival was observed in three studies. Adverse reactions were mild and usually controllable fever and fatigue. Besides, preclinical research progresses were reviewed to increase our understanding about the underlying mechanisms of CIK cell cytotoxicity and identify potential targets to enhance their anti-tumor activity. These studies suggest that CIK cell-based immunotherapy has potential clinical benefits with a good safety profile and could become a promising approach in the combined therapies of RCC patients. However, further large-scale studies are required to evaluate the clinical efficacy of CIK cells and more efforts should be performed to identify the optimal CIK cell-based therapeutic regimen for RCC patients.
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Reddy, Madhumitha, Ahmet Bindayi, Zachary Hamilton, Stephen Ryan, Kendrick Yim, Ryan Nasseri, Shreyas Joshi, et al. "Oncologic and functional outcomes of radical and partial nephrecotmy in PT3A patholigically upstaged renal cell carcinoma: A multi-instituitional analysis." Journal of Clinical Oncology 36, no. 6_suppl (February 20, 2018): 685. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.685.
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685 Background: Radical Nephrectomy (RN) has been the standard of care for complex and locally advanced renal cell carcinoma (RCC). Efficacy of PN in the setting of pT3a pathologic upstaged disease is controversial. We compared oncologic and functional outcomes of RN and PN in patients with upstaged pT3a RCC. Methods: Multicenter retrospective analysis of patients with cT1−2N0M0 RCC undergoing RN or PN upstaged to pT3a postoperatively. Primary outcome was Overall Survival (OS), with secondary outcomes being Recurrence Free Survival (RFS) and eGFR < 60 at last follow-up. Results: 8185 patients were analyzed (mean follow up 48 months). 945 (11.5%) were upstaged to pT3a [686 (72.6%) RN, 243 (25.7%) PN]. Logistic regression analysis showed that increasing age, decreasing BMI, increasing intraoperative EBL, and positive margin increased the OR of all-cause mortality (all p < 0.05, Table). Kaplan Meier analysis (KMA) revealed 5−year OS for PN cT1→pT3a, RN cT1→pT3a, PN cT2→pT3a, RN cT2→pT3a of 64%, 65.2%, 56.4% and 55.2% respectively (p = 0.059). KMA revealed 5−year RFS for PN cT1→pT3a, RN cT1→pT3a, PN cT2→pT3a, RN cT2→pT3a of 79%, 74%, 70% and 51% respectively (p < 0.001). PN was associated with a decreased risk of GFR < 60 at follow up (39.6% vs. 59.5% for RN, p = 0.008) Conclusions: PN did not adversely affect oncologic outcomes in select patients who are upstaged to pT3a RCC from cT1 or cT2 disease, and may provide renal functional benefit. Improvements with respect to RFS for PN are most likely driven by selection bias. [Table: see text]
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Dabestani, Saeed, Christian Beisland, Grant Stewart, Umberto Capitanio, Petrus Jarvinen, Harry Nisen, Karim Bensalah, et al. "Prevalence, disease-free (DFS) and overall (OS) survival of contemporary high-risk renal cell carcinoma (RCC) patients eligible for adjuvant checkpoint inhibitor trials: A RECUR database analysis." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 636. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.636.
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636 Background: Designing adjuvant trials is challenging because of uncertainties of prevalence and outcome of high-risk RCC despite use of validated risk scores. Methods: RECUR is a European multicenter database capturing patient and tumour characteristics, recurrence patterns and survival of all patients treated with (partial) nephrectomy for non-metastatic RCC from 2006 to 2011 at each participating center. We evaluated prevalence, DFS and OS of RCC according to eligibility criteria of adjuvant trials IMMotion 010 (NCT03024996, IM), Checkmate 914 (NCT03138512, CM), Keynote-564 (NCT03142334, KN) and RAMPART (NCT03288532, RP), which all predominantly recruited high-risk clear cell RCC patients. Results: Of 2669 relevant patients in RECUR, 424(15.9%), 681(25.5%), 579(21.7%) and 1221(45.7%) met eligibility criteria for IM, CM, KN and RP respectively (p < 0.001). Median DFS and OS estimates (Kaplan-Meier) in RECUR corresponding to each trial placebo arm were 37.5 (95%CI 30.4–44.6) and 89.6 (95%CI 76.1–103.0) months for IM, 89.4 (95%CI 66.1–112.7) and 96.2 (95%CI 79.8–112.6) months for CM, 62.6 (95% CI39.6–85.6) and 86.6 (95%CI 74.3–98.9) months for KN and finally at 144 months (DFS not reached) and 123.8 (95% CI 110.1 – 137.4) months for RP. Additionally, at pairwise analysis of evaluated trials, DFS estimates were significantly different between all trials (p < 0.001) except between CM and KN (p = 0.125), while OS estimates did not differ significantly between all trials except between RP and the other three trials (p = 0.002). Conclusions: Percentages of eligible high-risk RCC patients in RECUR were low to moderate and, together with estimated placebo arm DFS and OS, varied due to differences in trial eligibility criteria. These differences may impact on the results and interpretation of the trials.
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Duarte, Cassandra, Nieves Martinez Chanza, Katharine Collier, Nazli Dizman, Nityam Rathi, Rana R. McKay, Justine Panian, et al. "Outcomes of patients with pancreatic-only oligometastatic renal cell carcinoma (RCC)." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 681. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.681.
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681 Background: Patients (pts) with RCC and oligometastatic pancreas metastases are treated with pancreatectomy, stereotactic body radiation therapy (SBRT), or systemic therapy. The optimal approach is not clear. We aimed to evaluate the comparative efficacy of the modalities in terms of progression-free survival (PFS) and overall survival (OS). Methods: This IRB-approved, multi-institutional, retrospective study evaluated pts with pancreatic-only RCC metastasis without concurrent metastases elsewhere. Data on pt demographics, tumor characteristics, treatment, and outcomes were collected. PFS and OS in pts treated with pancreatectomy vs. systemic therapy were compared by log rank tests. Results: Fifty-one pts from 9 institutions were included. All had clear cell RCC; 50 pts had nephrectomy; 30 pts (58.8%) and 18 pts (35.3%) had IMDC favorable and intermediate risk, respectively. Median time from RCC diagnosis to oligometastatic disease was 120 months (mo) (range: 0, 175). As initial treatment, 23 (45%) pts had pancreatectomy (mostly partial); 25 (49%) had systemic therapy (VEGFR TKI and/or immunotherapy); 1 had SBRT; 2 had other treatments. Too few pts had SBRT for comparison. With a median follow-up of 25 mo (2, 68), median PFS for the population was 25 mo (17, 42 95% CI). Median PFS was 36 mo (8, 43 95% CI) for surgery pts and 22 mo (17, NR 95% CI) for systemic therapy pts; this was not statistically significant (NS), p = 0.3. Median OS for the population was 121 mo (100, NR 95% CI). With a median follow-up of 51 mo (2, 217), OS was 121 mo (100, NR 95% CI) for surgery pts and not reached (64, NR 95% CI) for systemic therapy pts; NS, p = 0.52. Conclusions: In this retrospective series, RCC pts with oligometastatic pancreatic-only disease had similar PFS and OS outcomes from initial pancreatectomy or systemic therapy. RCC pts with pancreas-only metastases represent a unique patient population and studies informing the underlying biology are needed to optimize clinical management.
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Shinder, Brian, Sinae Kim, Arnav Srivastava, Hiren V. Patel, Tina M. Mayer, Biren Saraiya, and Eric A. Singer. "Factors associated with clinical trial participation for patients with renal cell carcinoma." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 670. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.670.
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670 Background: Clinical trials are critical for the development of new treatment paradigms for renal cell carcinoma (RCC). The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with RCC. The secondary objective was to examine survival outcomes in the clinical trial and control cohorts. Methods: The National Cancer Database (NCDB) was queried for patients with RCC who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to controls from the same institution based on clinical stage. Sociodemographic variables were compared between the two groups and univariate and multivariate logistic regression models evaluated factors associated with clinical trial participation. Kaplan-Meier product limit estimate was used to compare overall survival (OS) between the groups. Results: From 2004-2015, 681 patients enrolled in clinical trials were included for analysis. The mean age of trial patients was 56.4 compared to 62 in the matched cohort (p<0.0001). More patients in the trial group had a Charlson-Deyo comorbidity score of 0 (81.6% vs. 73.9%, p<0.0001). On multivariate analysis, male patients (OR 1.27; 95%CI 1.06-1.54, p=0.012) and white patients (OR 1.88, 95%CI 1.23-2.87; p=0.003) were more likely to participate in a trial. Having Medicaid (OR 0.42; 95%CI 0.27-0.64; p<0.0001) or Medicare (OR 0.6; 95%CI 0.46-0.77; p<0.0001) was negatively associated with clinical trial participation. Median OS was greater among clinical trial participants than that the control cohort (106.61 vs 87.62 months, p<0.0001). Conclusions: In this contemporary analysis of RCC patients from a national hospital registry database, we found that patient sociodemographic factors remain associated with clinical trial participation and that clinical trial participants experienced superior OS. Further work, both qualitative and quantitative, is necessary to identify clinical and non-clinical barriers to research participation in order to improve the validity of RCC trials.
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Muzaffar, Mahvish, Abdul Rafeh Naqash, Darla K. Liles, and Sumyra Kachru. "Metastatic pattern and tumor sidedness in colorectal cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e15147-e15147. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15147.
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e15147 Background: Tumor side has emerged as an important prognostic and predictive factor in metastatic colon cancer. We sought to study its impact on the metastatic pattern of colorectal cancer. Methods: The SEER database (version 8.3.5) was reviewed for patients with Stage IV colorectal cancer diagnosed between 2004-2015. We only included patients with labeled primary site, and excluded appendiceal, unlabeled and autopsy alone cases. Variables included in the analysis were: age, race, gender, grade, primary tumor side and sites of metastasis at diagnosis. Primary outcome analyzed was overall survival and disease specific survival.Cox proportional hazard regression model was employed to test the association between survival and side of cancer/ site of metastasis. Results: A total of 74,768 cases were identified who met the eligibility criteria. The mean age was 68.5 yrs. for right colon cancer (RCC),64.0 yrs. for left colon cancer (LCC). and 62.9 yrs. for rectal cancer. White race was predominant group for RCC, LCC and rectum. More females were vs men in RCC (52% vs 48%), LCC (44% vs 56%) and rectum (60% vs 40%). (The cox regression model suggested inferior outcome for black race HR 1.05(1.03-1.07) (<0.001), high grade HR 1.32(1.30-1.35) p<.0001, right side tumors HR 1.23(1.21-1.250, p <.0001 (table). Conclusions: Over last few years tumor sidedness has emerged as an important prognostic and predictive factor in colon cancer. Our study also highlights the impact of sidedness on survival irrespective of distant metastatic pattern. This analysis contributes to the ongoing discussion that right and left colon cancer are two distinct disease entities. Impact of primary tumor side and metastatic site on survival in colorectal cancer. [Table: see text]
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Que, Xuchu, John Samuelson, and Sharon Reed. "Molecular cloning of a rac family protein kinase and identification of a serine/threonine protein kinase gene family of Entamoeba histolytica." Molecular and Biochemical Parasitology 60, no. 2 (August 1993): 161–70. http://dx.doi.org/10.1016/0166-6851(93)90128-k.
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Bustos, A., M. A. Cruz, P. Aramburo, F. Carabantes, N. Díaz, J. Florián, M. Lázaro, J. M. Martín de Segovia, J. A. Gasquet, and A. Alegre. "Evaluation of clinical use of darbepoetin alfa in patients with chemotherapy-induced anemia." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e20585-e20585. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e20585.
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e20585 Background: Chemotherapy-induced anemia (CIA) is a frequent complication of patients (pts) with cancer and could be treated with erythropoiesis-stimulating agents such darbepoetin alfa (DA). The aim of this study was to investigate the patterns of use and effect of DA to treat CIA in clinical practice conditions. Methods: This was an observational, retrospective, multicenter study performed in 58 Spanish centres. Eligible pts were ≥18 yrs, diagnosed with non-myeloid malignancies and treated with chemotherapy (CT) and DA from October 2005 to October 2006. Data on demographic and clinical characteristics, CT and radiotherapy (RT), DA administration, red blood cell (RBC) transfusions, and haemoglobin (Hb) levels were collected from DA treatment initiation up to a maximum of 16 weeks or until treatment discontinuation. Results: A total of 685 pts were included in the study. Median age was 64.66 years (range 18.54–88.95), 50.7% were women, 74.11% had ECOG status 0–1 and 71.38% had stage III/IV cancer. Solid tumours represented 72.55% of the cases. The CT regimen included platinum derivates in 33.58% of the pts. At DA initiation, mean (SD) Hb was 10.00 g/dL (1.05) Administration of DA every three weeks occurred in 54.01% of the pts. Mean (SD) DA administration was 9.20 weeks (5.31). Hematopoietic response (defined as Hb ≥ 12 g/dL or Hb rise from baseline >2 g/dL in the absence of RBC transfusions during the previous 28 days) occurred in 63.24% (95% CI 59.49–66.83) of pts. A total of 88 pts (12.85%) required RBC transfusions from week 5 to end of treatment. Mean Hb (SD) at the end of treatment with DA was 11.36 g/dL (1.73). Adverse event (AE) potentially related to DA were reported in 20 pts (2.92%) and considered severe in 6 cases (0.88%). Conclusions: The findings of this study indicate that the use of DA for the treatment of CIA in real-life, daily oncology and haematology practice, is well-tolerated and effective for increasing haemoglobin to reduce the need of RBC transfusions. [Table: see text]
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Gatto, Francesco, Sinisa Bratulic, Eric Jonasch, Angelo Limeta, Francesca Maccari, Fabio Galeotti, Nicola Volpi, Sven Lundstam, Jens Nielsen, and Ulrika Stierner. "Plasma and urine free glycosaminoglycans as monitoring and predictive biomarkers in metastatic renal cell carcinoma: A prospective observational study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e16540-e16540. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16540.
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e16540 Background: No liquid biomarkers are approved in renal cell carcinoma (RCC). In metastatic RCC (mRCC), there is a need to predict and monitor response noninvasively to guide the choice of treatment. Urine and plasma glycosaminoglycan (GAGs) profiles – or GAGomes - are promising biomarkers reflective of RCC metabolism. Here, we explored if GAGomes could predict and monitor response noninvasively. Methods: A single-center prospective consecutive series of mRCC patients elected for first-line therapy was enrolled between June 2016 - April 2019 at Sahlgrenska University Hospital, Gothenburg, Sweden. Response was assessed by the investigator as progressive disease (PD) versus non-PD. Plasma and urine GAGomes were measured at treatment start, after 6 weeks, and every 3rd month in a blinded central laboratory. We conducted Bayesian estimation to correlate GAGomes to response and to design GAG scores to classify PD. So-trained GAG scores were validated to predict PD vs. non-PD at treatment start or after 6 weeks. Results: Fifty patients with treatment-naïve mRCC were enrolled (median age: 68.5 years, 33% female). All received tyrosine-kinase inhibitors (37 sunitinib, 4 pazopanib, 9 cabozantinib). The median follow-up time was 3.5 months, totaling 65 response evaluation visits - 23 PD and 42 non-PD. PD was compatible with alterations in 40% of the detectable GAGome features. These were used to design a plasma, urine, and combined GAG progression score to classify PD vs. non-PD at response evaluation. The area-under-the-curve (AUC) was 0.91 in plasma, 0.98 in urine, and 0.99 when combined. In validation, the AUC to predict PD at treatment start was 0.64 in plasma, 0.63 in urine, and 0.71 when combined (N = 50); and, after 6 weeks, 0.75 in plasma, 0.66 in urine, and 0.80 when combined (N = 47). The combined GAG progression score had 62% sensitivity and 86% specificity to PD at treatment start and 67% and 87% after 6 weeks. Conclusions: GAGomes correlated with treatment response in mRCC. GAG scores were validated for the early prediction of response. Their clinical utility remains to be ascertained. Clinical trial information: NCT02732665.
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Ebert, Jay R., Anne Smith, Gregory C. Janes, and David J. Wood. "Association Between Isokinetic Knee Strength and Perceived Function and Patient Satisfaction With Sports and Recreational Ability After Matrix-Induced Autologous Chondrocyte Implantation." Orthopaedic Journal of Sports Medicine 7, no. 12 (December 1, 2019): 232596711988587. http://dx.doi.org/10.1177/2325967119885873.
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Background: Returning to a sound level of activity after matrix-induced autologous chondrocyte implantation (MACI) is important to patients. Evaluating the patient’s level of satisfaction with his or her sports and recreational ability is critical. Purpose: To investigate (1) satisfaction with sports and recreational ability after MACI and (2) the role that knee strength plays in self-reported knee function and satisfaction. Study Design: Case-control study; Level of evidence, 3. Methods: Isokinetic knee strength was assessed in 97 patients at 1, 2, and 5 years after MACI to calculate hamstrings-quadriceps ratios and peak knee extensor and flexor torque limb symmetry indices (LSIs). The Sports and Recreation subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS Sports/Rec) was completed. A satisfaction scale was used to evaluate how satisfied the patients were with their ability to return to recreational activities and their ability to participate in sport. Associations between knee strength LSI, KOOS Sports/Rec, and satisfaction with recreational and sporting activities were assessed through use of multivariable linear and logistic regression, with adjustment for confounders. Mediation analysis was conducted to assess the extent to which self-reported knee function mediated associations between strength LSI and satisfaction. Results: Satisfaction with the ability to return to recreational activities was achieved in 82.4%, 85.6%, and 85.9% of patients at 1, 2, and 5 years, respectively, and satisfaction with sports participation was achieved in 55.7%, 73.2%, and 68.5% of patients at 1, 2, and 5 years, respectively. Knee extension torque LSIs were associated with KOOS Sports/Rec after adjustment for confounders over 1, 2, and 5 years (5-year regression coefficient, 6.0 points; 95% CI, 1.4-10.7; P = .012). KOOS Sports/Rec was associated with the likelihood of being satisfied at all time points (recreation: 5-year adjusted odds ratio [OR], 2.26; 95% CI, 1.48-3.46; P < .001; and sports: 5-year adjusted OR, 1.98; 95% CI, 1.47-2.68; P < .001). In a multivariable mediation model, the knee extension torque LSI was associated with satisfaction directly (standardized coefficient, 0.16; 95% CI, 0.03-0.28; P = .017) and indirectly via KOOS Sports/Rec (standardized coefficient, 0.19; 95% CI, 0.01-0.38; P = .027), the latter representing 55% of the total association of knee extension torque LSI with satisfaction. Conclusion: Knee extensor symmetry was associated with satisfaction in recreational and sporting ability, both directly and indirectly, via self-reported sports and recreation–related knee function. Restoring strength deficits after MACI is important for achieving optimal outcomes.
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Elston, Robert, and Varghese George. "Authors' reply: Confidence limits based on the first occurrence of an event. V.T. George and R.C. Elton.Statistics in Medicine,12, 685-690 (1993)." Statistics in Medicine 17, no. 8 (April 30, 1998): 945. http://dx.doi.org/10.1002/(sici)1097-0258(19980430)17:8<945::aid-sim1823>3.0.co;2-5.
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Zenevicz, Leoni Teresinha, and Walter Ferreira dos Santos. "Crença em símbolos espirituais no processo de envelhecimento." Revista FisiSenectus 1, no. 1 (July 30, 2013): 51. http://dx.doi.org/10.22298/rfs.2013.v1.n1.1500.
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Objetivos: este estudo teve o objetivo de identificar e conhecer a crença dos idosos em símbolos espirituais que expressam sua espiritualidade e religiosidade, utilizando-os em diferentes situações para vencer os obstáculos da idade, fortalecendo-os e proporcionando bem-estar físico, mental e espiritual. Sabe-se que o ser humano é um ser religioso e os símbolos sagrados são respeitados por representarem a existência de uma força superior acenando a possibilidade do homem conectar-se com o divino, ocupando um lugar de destaque na vida terrena. Materiais e métodos: este estudo foi observacional do tipo transversal, realizado na cidade de Chapecó (SC), no período de julho de 2008 a janeiro de 2009. Fez parte da amostra 2.160 pessoas de idades 20 a 39, de 40 a 59 e acima de 60 anos, implicando em 720 indivíduos entrevistados em cada faixa etária nas suas residências. Na conferência do banco de dados, optou-se pela análise descritiva univariada, com a obtenção das frequências simples e relativas para cada variável investigada, e os dados finais receberam tratamento estatístico utilizando-se o software SPSS 13.0 (Statistical Package to Social Sciences for Windows). Resultados: a partir dos resultados, observou-se que 68,5% dos pesquisados acreditam em símbolos espirituais. 47,3% apontam a Bíblia como símbolo mais reverenciado em que depositam sua crença e fé e 73,9% confirmam que os símbolos os ajudam no enfrentamento das diferentes situações da vida cotidiana. Conclusão: frente aos achados, pode-se inferir que, com o aprofundamento do envelhecimento, os idosos tornam-se mais espiritualizados e olham com mais serenidade para a vida ampliando a fé, aproximando-se de Deus, acreditando nos símbolos e forças espirituais, exercitando mais suas práticas religiosas (preces, orações, súplicas).
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Ptaszek, Bartłomiej, Aneta Teległów, and Jakub Marchewka. "Impact of systemic cryotherapy on the rheological properties of the blood in women with rheumatoid arthritis." Rehabilitacja Medyczna 21, no. 2 (September 25, 2017): 4–9. http://dx.doi.org/10.5604/01.3001.0010.4815.
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Study aim: The aim of this study was to assess the effects of systemic cryotherapy on the rheological properties of the blood in women with rheumatoid arthritis. Study group: The study group consisted of 10 women with rheumatoid arthritis, aged 57.2 ± 9.4, who underwent systemic cryotherapy treatments (3 min treatment time, -120 °C chamber temperature, 10 treatment sessions - 5 times a week). Their average body height was 165.5 ± 4.6 cm, weight 68.5 ± 4.9 kg and BMI 24.8 ± 2.2 kg/m2. In order to analyze morphological and rheological parameters of the blood, venous blood samples were drawn from the participants of the study twice. The first study was held on the day of beginning treatments and the second test was conducted after a series of 10 treatments. Methodology: The morphological blood test - measurements were taken using the ABX MICROS 60 (USA) hematology analyser. Erythrocyte deformability and aggregation were tested using the LORCA analyser (Laser-assisted Optical Rotational Cell Analyser RR Mechatronics, The Netherlands). The results were obtained as the index of elongation and aggregation according to the Hardeman method (2001). Results: Analysing the average values of morphological and rheological parameters of the blood in women with rheumatoid arthritis in the study group, the mean values of RBC, Hct and AI following the series of 10 treatments were significantly higher after cryotherapy in comparison to the measurements taken before treatments. Analysing the mean concentrations of T½, there was statistically significant reduction after the series of 10 treatments. Conclusions: Regular usage of cryotherapy treatments may affect the levels of morphological and rheological parameters of the blood in women with rheumatoid arthritis - RBC, Hct and AI (increase) and T½ (reduction) in the blood. null
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Maroto-Rey, P., J. Bellmunt, J. M. Trigo, V. Guillem, J. A. López-Martín, J. Carles, A. Antón-Torres, and L. Urruticoechea. "First-line phase II trial of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma unsuitable for cytokine treatment." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 15640. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15640.
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15640 Background: Sorafenib (BAY 43–9006) is a serine/threonine and receptor tyrosine kinase inhibitor that prevents tumor cell proliferation and angiogenesis. The objective of this open-label, phase II trial was to determine median progression-free survival (PFS) following sorafenib therapy in patients with renal cell carcinoma (RCC) unsuitable for cytokine treatment. Methods: Eligible patients had cytologically or histologically confirmed clear cell RCC; Eastern Cooperative Oncology Group (ECOG) Performance Status 0–1; adequate renal, liver and medullar function; no active central nervous system metastases; had received no previous treatment with antiangiogenic agents; and had at least one evaluable lesion. Sorafenib was given as first-line treatment in patients unsuitable for cytokine therapy, defined as being intolerant to or ineligible for immunotherapy. Treatment consisted of oral sorafenib 400mg twice daily continuously until disease progression or unacceptable toxicity. The primary endpoint was PFS; secondary endpoints were response rate according to Response Evaluation Criteria in Solid Tumors, tolerability and overall survival. Results: Twenty-six patients were enrolled between March and July 2006 (median age: 68.5 years [48–82]; male/female: 17/9, ECOG Performance Status 0: 11 patients; prior nephrectomy: 19 patients). The main metastatic locations were lung and bone, 14 patients had = 2 metastatic lesions, and 2 patients had abnormal lactate dehydrogenase levels. As of 31 December 2006, with a median follow-up of 6.4 months, the median PFS had not been reached. In 19 patients evaluable for response, the overall clinical benefit rate was 68.4% (1 complete response; 1 partial response; 11 stable disease). Six patients experienced serious adverse events, only one of which was related to treatment. Conclusions: Sorafenib first-line therapy is a tolerable alternative for patients unsuitable for cytokine treatment. Final PFS data will be available in June 2007. No significant financial relationships to disclose.
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Shaikh, Fyza, James White, Joell Gills, Taiki Hakozaki, Richard Corentin, Bertrand Routy, Yusuke Okuma, et al. "681 Single pipeline re-analysis revises microbiome associations with anti-tumor response to checkpoint inhibitors." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A720. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0681.
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BackgroundSeveral studies suggest the gut microbiome may be a novel, modifiable biomarker for clinical efficacy of immune checkpoint inhibitors (ICIs). Microbiome profiling of pre-treatment samples demonstrated that high alpha-diversity and enrichment of specific bacterial species are associated with improved tumor responses in melanoma, renal cell cancer (RCC), and non-small cell lung cancer (NSCLC). Despite these reports, the specific bacteria or communities helpful or harmful have been inconsistent across study populations, and further correlation with immune and mutational biomarkers are limited or lacking. We hypothesize that, by use of a larger sample size and a consistent computational approach, we would derive a clearer microbial profile that correlated with immunotherapeutic outcomes.MethodsWe re-analyzed the available raw 16S rRNA amplicon and metagenomic sequencing data across five recently published ICI studies (n=303 unique patients) of responder (R) and nonresponse (NR) using a consistent computational approaches (Resphera Insight and MetaPhlAn2). Using novel microbiota signatures, we identified Re-analysis Indices for R- and NR-associated bacteria and validated the result in three addition cohorts with available raw sequencing data in patients with melanoma, hepatocellular cancer (HCC), and NSCLC (n=105).ResultsOur results confirm signals reported in each study, though some bacteria reported initially were not statistically significant after correction for false discovery rate. Likely, in part, because our analysis allows for comparison of individual species across cohorts, we were able to identify new bacterial signatures, such as Oxalobacter formigenes, Roseburia hominis and Veillonella parvula, Clostridium hathewayi, enriched in R and NR respectively. When our Re-analysis Index was compared to an index assembled from the literature, we noted improvement occurred in a sensitivity and specificity analysis, especially in NR-associated signals. Moreover, we found that alpha-diversity was not consistently predictive of response or nonresponse to ICIs. Our Re-analysis Index also validated in melanoma patients and HCC but did not perform as well in the NSCLC cohort, suggesting the need for further refinement based on tumor type.ConclusionsIn summary, this bioinformatics platform improves on existing pipelines by standardizing critical preprocessing and downstream analysis tools, enabling comprehensive evaluations of taxonomic and functional signals across sequencing datasets. Notably, the NR-associated Re-analysis Index shows the strongest and most consistent signal using a random effects model and in a sensitivity and specificity analysis (p < 0.01). Our integrated analyses suggest an approach to identify patients who would benefit from microbiome-based interventions targeted to improve response rates by using a biomarker for nonresponse.
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Longo, Nicola, Marco Capece, Giuseppe Celentano, Roberto La Rocca, Gianluigi Califano, Claudia Collà Ruvolo, Carlo Buonerba, et al. "Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review." Cancers 12, no. 12 (December 4, 2020): 3634. http://dx.doi.org/10.3390/cancers12123634.
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A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.
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Hutson, Thomas E., M. Dror Michaelson, Timothy M. Kuzel, Neeraj Agarwal, Ana M. Molina, James J. Hsieh, Ulka N. Vaishampayan, et al. "A phase II study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma (nccRCC)." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 685. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.685.
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685 Background: Non-clear cell renal cell carcinoma (nccRCC) is an umbrella term that encompasses multiple RCC histological subtypes, including papillary, chromophobe, and undetermined RCC. Both increased expression of the vascular endothelial growth factor (VEGF) and dysregulation of the mammalian target of rapamycin (mTOR) pathway occur in nccRCC. Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor that inhibits the VEGF receptor and other targets; everolimus (EVE) is a mTOR inhibitor. LEN + EVE is approved for the treatment of patients with advanced RCC following 1 prior antiangiogenic therapy. This phase 2 study examined the efficacy and tolerability of LEN + EVE in patients with nccRCC. Methods: This single-arm, multicenter, phase 2 trial assessed the safety and efficacy of LEN (18 mg once daily) + EVE (5 mg once daily) in patients with unresectable advanced or metastatic nccRCC who had not received any chemotherapy for advanced disease. The primary objective was objective response rate (ORR) as assessed by investigators using RECIST v1.1. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety assessments. Results: At the time of data cutoff (July 17, 2019), 31 patients with nccRCC (papillary, n = 20; chromophobe, n = 9; unclassified, n = 2) were enrolled and treated. The ORR was 25.8% (95% confidence interval [CI]: 11.9–44.6%); 8 patients achieved a partial response (PR; papillary, n = 3; chromophobe, n = 4; unclassified, n = 1) and no patients had a complete response (CR). The median duration of response was not reached. Additionally, 18 patients (58.1%) had stable disease (SD) and the clinical benefit rate (CR + PR + durable SD [duration ≥ 23 weeks]) was 61.3% (95% CI: 42.2–78.2%). The median PFS was 9.23 months (95% CI: 5.49- not estimable [NE]) and median OS was 15.64 months (95% CI: 9.23–NE). The safety profile observed in this study was similar to the established profile of the study drug combination (LEN + EVE). Conclusions: The combination of LEN + EVE showed promising antitumor activity as first-line therapy in patients with advanced nccRCC. The ORR was 25.8%, which compares favorably to historical reports with EVE monotherapy. Clinical trial information: NCT02915783.
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Santoro, Cristina, Angela Rago, Angela Antenucci, Antonio Chistolini, Laura Conti, Annalisa De Vellis, Lucia Di Renzo, et al. "Prevalence of Anti-HLA and Anti-GPIIB/IIIA Allo-Immunization in Patients with Glanzmann Thromboasthenia: Experience of a Single Center." Blood 108, no. 11 (November 16, 2006): 3980. http://dx.doi.org/10.1182/blood.v108.11.3980.3980.
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Abstract Background. Platelet transfusions, the main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against HLA antigens and GPIIb/IIIa complexes, with a possible reduction of efficacy of subsequent treatments. Aims. To investigate the development of anti-HLA antigen and anti-GPIIb/IIIa complexe allo-immunization in GT transfused patients, and to evaluate the efficacy of replacement therapy. Patients and Methods. From 1975 onwards, we have followed 17 GT patients; 13 type I, 3 type III, 1 not classified; 8 men, 9 women; median age at diagnosis 9.8 years (range 1–44.5); the median age at the time of this study was 35.5 years (range 23.6–68.5). Our patients had shown at least once in their life the following symptoms: 10/17 epistaxis; 5/17 gastrointestinal hemorrhage; 5/17 oropharingeal hemorrhage; 4/17 muscle hematoma; 2/17 bleeding for traumatic injury; 2/17 hemarthrosis; 2/17 hematuria; 1/17 intracranial hemorrhage; 1/17 hematothorax; 1/17 otorrhagia. Five out of 9 women had experienced meno-metrorrhagia. Ten major and 22 minor surgical procedures had been performed. Two spontaneous deliveries and 3 cesarian sections with 5 live births had been reported; moreover, 2 abortions had occurred, 1 spontaneous and 1 voluntary. Globally, 9/17 patients had been transfused with platelets and red blood cells (RBC); 5/17 only with platelets; 2/17 only with RBC. One patient has never been transfused. Platelet transfusions have always been hemostatically effective. All transfused patients have been investigated for anti-HLA and anti-GPIIb/IIIa allo-antibodies,. Results. Positivity for allo-antibodies could be demonstrated in 4/15 patients (27%): isolated for anti-HLA in 2; isolated for anti-GPIIb/IIIa in 1; combined in 1. Conclusions. The prevalence of allo-immunization (27%) is inferior to recent literature data (50%). While positivity for anti-HLA (3/15, 20%) agrees with the recently reported data (22%), positivity for anti-GPIIb/IIIa (13%) is inferior (35%). Presence of allo-immunization did not compromise the efficacy of platelet transfusions.
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Atkins, Michael B., Igor Puzanov, Elizabeth R. Plimack, Mayer N. Fishman, David F. McDermott, Daniel C. Cho, Ulka N. Vaishampayan, et al. "Axitinib plus pembrolizumab in patients with advanced renal cell carcinoma: Long-term efficacy and safety from a phase Ib study." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 5080. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5080.
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5080 Background: Axitinib (AXI) plus pembrolizumab (pembro) showed superior overall survival (OS), progression-free survival (PFS) and response rate compared with sunitinib in a randomized Phase 3 trial in advanced renal cell carcinoma (RCC). Here, we report long-term efficacy and safety data of the combination AXI/pembro from the Phase 1 trial, with almost 5 years of follow-up. Methods: 52 treatment-naïve patients with advanced RCC were enrolled between 23 September 2014 and 13 October 2015, and were treated with oral AXI 5 mg twice daily and intravenous pembro 2 mg/kg every 3 weeks. Planned treatment duration was 2 years for pembro and not limited for AXI. Based on International Metastatic Database Consortium (IMDC) criteria, 46.2%, 44.2% and 5.8% of patients were reported as having favourable, intermediate and poor risk. Results: At data cut-off date (July 3, 2019), median OS was not reached; 38 (73.1%) patients were alive. 14 (26.9%) patients had died, none were related to treatment. The probability of being alive was 96.1% (95% CI 85.2–99.0) at 1 year, 88.2% (95% CI 75.7– 94.5) at 2 years, 82.2 % (95% CI 68.5– 90.3) at 3 years, and 66.8 % (95% CI 49.1–79.5) at 4 years. Median PFS was 23.5 (95% CI 15.4–30.4) months. Median duration of response was 22.1 (95% CI 15.1–not evaluable) months. Median time on treatment with the combination AXI/pembro was 14.5 months (n=52), median time on pembro after AXI discontinuation was 9.0 months (n=10), and median time on AXI after pembro discontinuation was 7.5 months (n=11). After stopping study treatment, 22 patients received subsequent systemic therapy, including nivolumab and cabozantinib (n=6 each). Grade 3/4 AEs were reported in 38 (73.1%) patients. 20 (38.5%) patients discontinued either drug due to AEs: 17 (32.7%) patients discontinued AXI, and 13 (25.0%) patients discontinued pembro with 10 (19.2%) discontinuing both drugs. Dose reduction of AXI due to AEs was reported in 16 (30.8%) patients. The most common AEs reported were diarrhea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%), and dysphonia (48.1%). Increased alanine aminotransferase and aspartate aminotransferase occurred in 44.2% and 36.5% of patients, respectively. With this longer follow-up, there were no cumulative AEs or new AEs. OS by IMDC risk group will be presented. Conclusions: In patients with advanced RCC with almost 5 years of follow-up, the combination of AXI/pembro continues to demonstrate clinical benefit with no new safety signals. Clinical trial information: NCT02133742 .
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Karam, Laura Beatriz, Tallita Karoline Nunes, Renata Di Lena Paiva, Raquel Szygalski Biasi, Cristiano Gomes, Luciana Do Amaral Gurgel Galeb, and Diana Thomé Fachin. "AVALIAÇÃO DA INFORMAÇÃO NUTRICIONAL DE MARCAS COMERCIAIS DE REQUEIJÃO CREMOSO Evaluation of nutritional information of commercial brands of requeijão." Revista Acadêmica: Ciência Animal 10, no. 3 (July 15, 2012): 293. http://dx.doi.org/10.7213/academica.7706.
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Originalmente brasileiro, o requeijão cremoso é um queijo fundido que apresenta elevado teor de gordura e, como produto embalado, deve apresentar informação nutricional a fim de promover a comunicação, ao consumidor, sobre o valor energético e os componentes que constituem o produto. Este trabalho objetivou avaliar as informações nutricionais apresentadas nos rótulos de marcas comerciais de requeijão cremoso e a confiabilidade das informações. Foram determinados o valor energético, carboidratos, proteínas, gorduras totais, gorduras saturadas, gorduras trans e extrato seco total, de sete marcas comerciais de requeijão cremoso. Calculou-se a variação dos resultados obtidos com as quantidades apresentadas nos rótulos dos produtos e comparou-se com o limite permitido no Padrão de Identidade e Qualidade (PIQ) do produto. No estudo, foram obtidas 49 respostas que resultaram das comparações entre os resultados obtidos por métodos analíticos e as informações dos rótulos ou limites permitidos por legislação. Desse total, dez respostas apresentaram variação fora dos 20% tolerados pela RDC 360/2003, podendo-se concluir que 20,4% das informações nutricionais dos rótulos das sete marcas comerciais de requeijão cremoso analisadas não estavam adequadas à legislação vigente. A partir das análises realizadas nas sete marcas comerciais de requeijão cremoso, pode-se definir que a composição da porção de 30 g do produto variou entre 68,5 – 85,0 kcal de valor energético; 0 – 1,2 g de carboidratos; 1,7 – 3,3 g de proteína; 6,5 – 8,0 g de gorduras totais; 3,9 – 5,3 g de gordura saturada e 0,19 a 0,30 g de gordura trans.
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Ma, Jie, Yanna Dou, Hanjie Zhang, Stephan Thijssen, Schantel Williams, Viktoriya Kuntsevich, Georges Ouellet, et al. "Correlation between Inflammatory Biomarkers and Red Blood Cell Life Span in Chronic Hemodialysis Patients." Blood Purification 43, no. 1-3 (2017): 200–205. http://dx.doi.org/10.1159/000452728.
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Background and Objectives: The pathogenesis of anemia in hemodialysis (HD) patients is dependent on multiple factors, with decreased red blood cell life span (RBCLS) being a significant contributor. Although the impact of reduced RBCLS on anemia is recognized, it is still a subject that is not well researched. The objective of this study was to investigate the relationship between RBCLS and inflammatory biomarkers in chronic HD patients. Design, Setting, Participants, and Measurements: RBCLS was calculated from alveolar carbon monoxide concentrations measured by gas chromatography. Interleukins (IL) IL-6, IL-18, IL-10, and high sensitivity C-reactive protein were measured using bead-based multiplex assay. Measurements were carried out at baseline and during follow-up. The associations between RBCLS and inflammatory biomarkers were evaluated using linear mixed effects models. Results: RBCLS measurements were available for 54 HD patients. Their average age was 58.5 ± 14.4 years, 68.5% were males, 48.1% were diabetics, and the HD vintage was 51 ± 48 months. In 4 patients, RBCLS was measured once, while in 50 patients, up to 5 repeated RBCLS measurements were available. RBCLS was 73.2 ± 17.8 days (range 37.7-115.8 days). No association was found between RBCLS and any of the inflammatory biomarkers. Of note, RBCLS was positively correlated with levels of uric acid (p = 0.02) and blood urea nitrogen (BUN; p = 0.01), respectively. Conclusion: Our study suggests that inflammation pathways reported by these biomarkers only have a limited role in causing premature RBC death. The positive correlation with uric acid and BUN warrants further studies.
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Harshman, Lauren C., Calvin J. Kuo, Bryan Y. Wong, Nicholas J. Vogelzang, and Sandy Srinivas. "Increased Hemoglobin Associated with VEGF Inhibitors in Advanced Renal Cell Carcinoma." Blood 112, no. 11 (November 16, 2008): 3453. http://dx.doi.org/10.1182/blood.v112.11.3453.3453.
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Abstract Agents that inhibit vascular endothelial growth factor (VEGF) are now standard of care for the treatment of advanced renal cell carcinoma (RCC). Two VEGF tyrosine kinase inhibitors (TKIs), sunitinib and sorafenib, are now FDA approved for metastatic RCC. Sunitinib increases overall survival compared to interferon-α in the first line setting, and both improve response and progression-free survival (PFS). A monoclonal antibody against VEGF, bevacizumab, is still investigational but has recently been shown to improve PFS in combination with interferon-α. These and other investigational VEGF inhibitors continue to be actively investigated as monotherapies and in combination with other targeted agents for the treatment of advanced RCC among other cancers. Surrogate biomarkers that accurately predict therapeutic VEGF inhibition and anti-tumor response to these inhibitors would be useful. Preclinical work at our institution revealed that extremely stringent VEGF inhibition in mice resulted in increased hemoglobin and erythropoietin (Epo). This Epo production originated in the liver, not the kidney, implicating endogenous VEGF as a previously unsuspected repressor of hepatic Epo synthesis and suggested that hemoglobin and Epo may be non-invasive markers for VEGF inhibition in vivo. We retrospectively reviewed whether hemoglobin levels increased in patients receiving bevacizumab as monotherapy or in combination with epidermal growth factor receptor (EGFR) or dose-reduced (or eventual dose-reduced) VEGF TKIs for advanced RCC. Twelve patients with advanced RCC were eligible for retrospective review. Demographic data, baseline anemia, initial and treatment hemoglobin levels, response, and confounding factors such as recent chemotherapy, blood transfusions, iron supplementation, or growth factor use were assessed. Correlation between the degree of change in hemoglobin from baseline to peak level and PFS were evaluated. The majority of patients were male and treatment naïve (67%). Fifty percent of patients had bone metastases, and 50% had baseline anemia. Five patients were on concurrent treatment with sunitinib, sorafenib, or erlotinib. Hemoglobin rose on bevacizumab in 11 patients. The median change in hemoglobin was 1.6 g/dL (0–2.7). The median percent rise was 12.3%; 10.9% in the monotherapy cohort and 18.6% in the combination group. For all 12 patients, the median time to initial increase in hemoglobin was 35 days (0–168 days) and 82 days (0–476 days) from baseline level to peak level. Median time to peak hemoglobin (first rise to peak) was 68.5 days (0–308 days). Median duration of hemoglobin rise was defined as the first rise in hemoglobin to the first decline in levels after peak and was 113 days (n=10, range: 28–350 days). The best response was disease stabilization in 8 patients. In the metastatic patients, degree of peak increase correlated with longer PFS: a 5–15% increase yielded a 3.1 month median PFS whereas a greater than 15% increase corresponded to an 8.2 month median PFS. In conclusion, the majority of patients (92%) on bevacizumab monotherapy or in combination with dose-reduced VEGF or full-dose EGFR tyrosine kinase inhibitors experienced an increase in hemoglobin from their pre-treatment baseline suggesting a correlative effect. The combination group was expected to have less of an increase in hemoglobin as sunitinib and sorafenib are known to cause anemia via c-Kit inhibition. We hypothesize that the reduced doses of these agents when used in combination with bevacizumab were inadequate to cause significant anemia but were sufficient to induce more complete VEGF inhibition in these patients. This is the first human study to identify increased hemoglobin as a possible consequence of treatment with VEGF inhibitors. The correlation between degree of increase in hemoglobin and longer PFS suggests that hemoglobin may be useful as a surrogate marker of stringent VEGF inhibition and as a predictive factor for clinical response. This relationship warrants validation in larger cohorts.
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Tang, Grace, Rachel Hart, Michelle Sholzberg, and Christine Brezden-Masley. "Iron deficiency anemia in gastric cancer: A single site retrospective cohort study." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 188. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.188.
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188 Background: Gastric cancer is highly prevalent amongst men and women. While many studies have identified the prevalence and association of iron deficiency anemia (IDA) in all cancer patients, few have focused on the gastric cancer population. The primary objective of this study was to determine the proportion of patients with gastric cancer who developed IDA, and chemotherapy induced anemia (CIA) at our institution. Secondary objectives were to identify types and frequencies of IDA therapies used. Methods: A retrospective study was carried out in 110 consecutive gastric cancer patients from 2006 to 2014 at St. Michael’s Hospital, Toronto, Canada. Patient demographics, previous history of IDA, and IDA based therapies were reviewed. IDA was defined as hemoglobin (Hb) < 130 g/L in men and < 120g/L in women and iron deficiency (ID) was defined as a ferritin < 15m/L. SAS 9.3 was used to calculate frequencies and proportions. Results: Of the 110 patients (median age 68.5 [interquartile range (IQR): 58-76]), 72 (65%) were male. Most patients were diagnosed at stage IV (35%) with a mean Hb of 118 g/L (standard deviation (SD): 19.7 g/L). Only 18 (16%) patients had a history of IDA prior to cancer diagnosis, and 63 (57%) had IDA at time of gastric cancer diagnosis. Only 29 patients (45%) had ferritin levels tested at first oncology visit. Of the 110 patients, 71 patients had an open (32%) or laparoscopic (68%) surgery. A total of 66 patients received chemotherapy, and 50 (76%) developed CIA. In this sample, 9 (14%) experienced a chemotherapy dose delay and 20 (30%) had a dose reduction. At last follow up, 87 (79%) of patients were diagnosed with IDA. Red blood cell (RBC) transfusions were most frequently prescribed (95%), compared to oral (29%) or intravenous iron (12%). Conclusions: A total of 87 (79%) gastric cancer patients were diagnosed with IDA and nearly all patients received a RBC transfusion. We found that the diagnosis of IDA increased by 22% from the time of gastric cancer diagnosis to last follow up. There was a high proportion of IDA in our gastric cancer population despite inconsistent screening for ID. This highlights the need for consistent screening and targeted therapy for ID to reduce transfusions and improve quality of life in this patient population.
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George, Saby, Jillian Faccone, Stephen Huo, Ying Zhang, Brian Stwalley, Melissa Hamilton, Trong Kim Le, and Flavia Ejzykowicz. "Real-world treatment patterns and sequencing for metastatic renal cell carcinoma (mRCC): Results from the Flatiron database." Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021): 286. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.286.
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286 Background: RCC accounts for ~80%‒90% of all kidney cancers worldwide. The mRCC treatment landscape is rapidly changing with the approval of new therapies; data describing real-world (RW) treatment patterns and sequencing are limited. This study investigates the characteristics, treatment patterns, and sequencing for mRCC patients in the RW (December 2015‒May 2020) and post-dual immuno-oncology therapy (IO-IO) approval in the United States (April 2018‒May 2020). Methods: Adults diagnosed with mRCC between December 2015 and May 2020 were selected from the Flatiron electronic medical record database for this retrospective study. The study cohort was required to have ≥ 1 month of medical data from the initial mRCC diagnosis date (index date). We used descriptive statistics to analyze baseline patient characteristics, treatment patterns, and sequencing. Results: Of 3,524 patients with mRCC (overall cohort, December 2015–May 2020), most were male (68.5%) and had clear cell histology (68.2%). The median age at metastatic diagnosis was 68 years (range, 23–85) and the median follow-up from index date was 328 days. Based on IMDC risk score, 75.8% of patients were categorized as intermediate/poor risk and 23.2% as favorable risk (1% missing). Systemic therapy for RCC was initiated in 79.1% (N = 2788) of patients. The most common treatments for first-line (1L) therapy were tyrosine kinase inhibitor (TKI) monotherapy (mono; 56.4%), IO-IO (19.1%), IO-TKI (9.5%), IO mono (6.9%), and others (8.1%). Second-line (2L) therapy was received by 1303 patients; treatment sequences are presented in the table below. Among patients who received IO-based therapy in the 1L (N = 990), 11% were retreated with IO on any subsequent line. When stratified by clear cell and non-clear cell histology, similar treatment patterns and sequences were observed. Among patients who initiated 1L treatment post-April 2018 (N = 1395), the most common treatments for 1L therapy were IO-IO (36.9%) and TKI mono (32.7%). Among patients who received 2L treatment after initiating 1L post-April 2018 (N = 486), TKI mono followed by IO mono, and IO-IO followed by TKI mono were the most prescribed sequences (Table). Conclusions: Following approval of IO-based therapies for 1L, RW treatment patterns for mRCC are evolving; IO-IO has become the most common 1L therapy received by all patients initiating treatment for mRCC. [Table: see text]
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Raychaudhuri, Ruben, Kathryn A. Bylow, William Lea, John Byun, Timothy Zellmer, John D. Burfeind, Matthew John Riese, and Deepak Kilari. "Liver-directed therapy (LDT) for metastatic renal cell carcinoma (mRCC): Single center experience." Journal of Clinical Oncology 36, no. 6_suppl (February 20, 2018): 681. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.681.
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681 Background: Liver metastases arising from RCC are common and signify a poor prognosis. Given the negative impact of liver metastases on overall survival (OS) and quality of life, it is reasonable to to consider therapies directly targeting these lesions in select patients. Little is known about how minimally invasive LDT affects outcomes in patients with mRCC. Methods: Nine patients with mRCC underwent LDT for liver-dominant or liver-only metastatic disease between 2005 and 2015. Retrospective chart review was performed under an IRB protocol to identify patient and disease characteristics, imaging response, and time to next systemic treatment, OS and toxicities. Patients were seen in clinic at one month post-LDT to monitor for toxicities. Imaging was obtained within 2 months prior to treatment and at 3 and 6 months following LDT. Results: Each patient underwent a median of 2.3 procedures. A total of 18 transarterial chemoembolizations (TACE) and 5 yttrium-90 radioembolizations were performed. 2 patients had metastatic disease confined to the liver, and 7 had liver-dominant disease. 7 had multifocal disease involving < 25% of the liver, and 2 had multifocal disease involving > 25% of the liver. 8/9 patients received prior systemic therapies, receiving a median of 3 (0-4) distinct treatments. 4/9 patients were undergoing systemic therapy at the time of LDT, 1 patient declined further treatment, and the median time to initiation of the next systemic therapy in the remaining patients was 3 months (range 2-4 months). Median OS from first line systemic therapy was 39 months, 95% CI [25.9-53.3], and the median OS from the first LDT was 22 months (from 5-45 months). Follow-up imaging post-LDT showed PR or SD in 88% of cases at 3 months and 44% of cases at 6 months. At one month post-procedure, 8/9 patients maintained performance status, and only one patient experienced CTCAE grade 3-4 toxicity. Conclusions: The median OS in RCC patients with liver disease and systemic therapy alone is 14.3 months. The improved median OS of 39 months with LDT in our unmatched and heavily pretreated cohort suggests a role for LDT. LDT is generally well tolerated and should be considered for patients with liver-dominant mRCC with good performance status.
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Perez-Gracia, Jose Luis, Aaron Richard Hansen, Rikke Helene Loevendahl Eefsen, Carlos A. Gomez-Roca, Sylvie Negrier, Paolo Pedrazzoli, Jae-Lyun Lee, et al. "Randomized phase Ib study to evaluate safety, pharmacokinetics and therapeutic activity of simlukafusp α in combination with atezolizumab ± bevacizumab in patients with unresectable advanced/ metastatic renal cell carcinoma (RCC) (NCT03063762)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4556. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4556.
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4556 Background: Simlukafusp α ([SIM], FAP-IL2v) is a novel IL-2v immunocytokine engineered to preferentially activate effector CD8 T and NK cells, but not regulatory T cells (Tregs), due to abolished binding to Interleukin-2 receptor α (IL-2Rα) and retained affinity to IL-2Rβγ. High affinity binding of SIM to fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, mediates its accumulation in malignant lesions. Methods: The Dose-Escalation (DE) consisted of: Arm A: SIM 5-25 mg weekly for 4 weeks, and every 2 weeks (Q2W) thereafter in combination with atezolizumab [ATZ] 840mg Q2W; and Arm B: same as Arm A + bevacizumab [BEV] 10 mg/kg Q2W. Patients (pts) not previously treated were evaluated in the Extension Part: Arm C (n=3): SIM + ATZ every 3 weeks (Q3W); or Arm D (n=25): SIM + ATZ + BEV (“triplet”) Q3W. Primary objectives were: finding the recommended dose of SIM and assessment of objective response rate (ORR) by RECIST v1.1. Results: We enrolled 69 pts with unresectable advanced/ metastatic clear-cell and/or sarcomatoid RCC. Median age of patients was 57 years (range: 35-78). The recommended dose for extension of SIM was 10 mg. Median treatment duration in days in each arm were: A: 106 (range: 1-877); B: 324 (8-940); C: 659 (71-768); D: 437 (1-682). Twenty-five pts are evaluable for therapeutic activity in Arm A [ORR: 24% (6 PR; 90% CI 12.95, 40.12)]; 15 in Arm B [46.7% (1 CR, 6PR; 90% CI 27.67, 66.68)]; 3 in Arm C [33.3% (1PR; 90% CI 7.83, 74.65)]; and 23 in Arm D [47.8% (2 CR, 9 PR; 90% CI 35.74, 68.15)]. Twelve patients are ongoing on study treatment. Treatment related grade 3 and 4 adverse events (AE) occurred respectively in 69.7% and 9.1% patients. The most common serious AEs were pyrexia (10.6 %) and infusion-related reactions (9.1%). 65.2% Of the patients reported at least one AE of elevations in liver transaminases/GGT/ alkaline phosphatase/bilirubin. Drug-related AEs led to dose modification/interruption in 37.9 % of the pts, and treatment discontinuation in 3% of the patients. SIM led to preferential expansion and activation of NK and CD8 T cells (but not Tregs) in peripheral blood and augmented tumor infiltration and tumor inflammation. Intriguingly responses were observed not only in pts with PD-L1 positive or inflamed tumors, but also in pts with PD-L1 negative tumors (n=13) or poorly infiltrated tumors classified as immune deserts (n=2). Conclusions: The combination of SIM with ATZ ± BEV was feasible with an acceptable safety profile. Clinical activity was more favorable for the triplet among the study Arms, but comparable to the ATZ + BEV combination in the IMmotion151 (Rini B, et al 2019). Observed pharmacodynamic findings were consistent with the expected effects. Clinical trial information: NCT03063762.
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Zarrabi, Kevin, Elizabeth A. Handorf, Benjamin Miron, Matthew R. Zibelman, Fern Anari, Pooja Ghatalia, Elizabeth R. Plimack, and Daniel M. Geynisman. "Real-world outcomes in patients with metastatic clear cell renal cell carcinoma receiving front-line axitinib plus pembrolizumab versus ipilimumab plus nivolumab." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4551. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4551.
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4551 Background: Front-line treatment for patients (pts) with metastatic clear cell renal cell carcinoma (mRCC) has undergone rapid advances in the last five years. This evolution has led to uncertainty about the optimal first line combination regimen. Herein, we compare real-world outcomes in pts treated with either axitinib/pembrolizumab (A/P) or ipilimumab/nivolumab (I/N) reported by International Metastatic RCC Database Consortium (IMDC) score. Methods: The nationwide Flatiron Health electronic health records-derived database was used to select pts diagnosed with mRCC and treated with front-line A/P or I/N from 2018-2020. The primary endpoints were overall-survival (OS) and real-world progression free survival (rwPFS). The survival analyses were adjusted using propensity score-based Inverse Probability of Treatment weighting, providing balance on age, gender, insurance, race, IMDC, practice type, and nephrectomy. Survival was assessed from beginning of therapy, and survival by treatment groups was compared using weighted and unweighted Kaplan-Meier curves with log-rank tests and weighted Cox proportional hazards regressions. Disease characteristics between the treatment groups were compared using chi-square and T-tests. Results: 821 pts received frontline A/P (n=259) or I/N (n= 562). Demographics and clinical parameters were similar between the two cohorts. Median age was 66 years, 73% were male, and 54.9% had a nephrectomy. 459 pts had all IMDC criteria factors available, 242 pts had missing factors but enough to define as intermediate/poor risk, 120 pts had unknown IMDC risk. Adjusted median OS was not statistically different: mOS for A/P was not reached (NR) while I/N was 22 mo (95% CI, 19.8-NR; p=0.40). Twelve-month survival was 68.5% for A/P treated pts and 65.8% for I/N treated pts (P=0.41). Twelve-month rwPFS was 41.4% for A/P treated pts and 39.7% for I/N treated pts (P=0.14). No statistical difference in survival was seen within IMDC risk strata (see table). Conclusions: In this retrospective, real-world study of pts treated with front-line A/P or I/N, 12-month survival was not statistically different irrespective of IMDC risk. Longer follow-up will be necessary to discern any significant differences.[Table: see text]
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Abu Rmilah, Anan Abdelmoti, Grace Lin, and Joerg Herrmann. "Risk of QTc interval prolongation among cancer patients treated with tyrosine kinase inhibitors." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 3033. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.3033.
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3033 Background: QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice. Methods: We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥ 450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥ 500 ms, rate of increase of the QTc interval by ≥ 60 ms, and the development of complications (VT, TdP and SCD). Results: In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥ 500 ms was documented in 53 (18.3%) and QTc progression ≥ 60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Conclusions: The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy. [Table: see text]
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Smith, Catherine C., Mark J. Levis, Mark R. Litzow, Alexander E. Perl, Jessica K. Altman, Stanley C. Gill, Takeshi Kadokura, et al. "Pharmacokinetic Profile and Pharmacodynamic Effects of ASP2215, a Selective, Potent Inhibitor of FLT3/AXL, in Patients with Relapsed or Refractory Acute Myeloid Leukemia: Results from a First-in-Human Phase 1/2 Study." Blood 126, no. 23 (December 3, 2015): 4836. http://dx.doi.org/10.1182/blood.v126.23.4836.4836.
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Abstract Introduction: ASP2215, a new tyrosine kinase inhibitor with activity against FMS-like receptor tyrosine kinase-3 (FLT3) and AXL receptor tyrosine kinase, is currently in development for the treatment of acute myeloid leukemia (AML). Methods: In an ongoing, first-in-human Phase 1/2, dose-escalation/dose-expansion study, the pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of ASP2215 were evaluated under fasting conditions in patients with relapsed or refractory AML (R/R AML). Patients who met study criteria were assigned to treatment in the dose-escalation cohorts or were randomized to an open dose level in the dose-expansion cohorts. The dose-escalation cohort was a modified 3+3 with accelerated titration design that evaluated ascending oral doses of ASP2215 (20-450 mg), the dose-expansion cohort was a parallel, multi-dose-expansion cohort. Blood samples were collected and safety/tolerability assessments, including 12-lead electrocardiogram, were evaluated at protocol-specified time points for both cohorts. Effect of increasing ASP2215 exposure on inhibition of FLT3 phosphorylation, assessed via plasma inhibitory assay (PIA), was evaluated using an inhibitory PK/PD Emaxmodel. PK/PD analyses were performed to evaluate the relationship between ASP2215 exposure and changes from baseline in QTcF intervals (ΔQTcF) and changes from baseline in clinical laboratory values (e.g., creatinine kinase [ΔCK], aspartate aminotransferase [ΔAST]). Results: Data from an interim analysis of the dose-escalation/dose-expansion study were available from 215 subjects (n=23 [dose escalation], n=192 [dose expansion]). The ASP2215 PK parameters across the dose range (20-450 mg), evaluated after both single- and multiple-dose administration, are presented (Table); statistical analyses suggest the ASP2215 PK parameters are dose proportional from 20-450 mg. Median time to maximal concentration (Tmax) was observed between 2 hr and 6 hr after single and repeated oral dosing. The estimated median half-life (t1/2) ranged from approximately 45 hr to 159 hr based on the accumulation ratio; ASP2215 accumulation was extensive after multiple dose administration as reflected by the accumulation index (Rac) ranging from approximately 3.2-10. A strong correlation was shown for ASP2215 exposure-related inhibition of FLT3 phosphorylation, with >90% FLT3 inhibition observed by Day 8 at ASP2215 doses of ≥80 mg. Although a positive slope was observed between ΔQTcF and ASP2215 exposure, only 5% of the study population were reported as having a maximum post-baseline QTcF interval >500 msec. A similar trend was observed with ASP2215 concentration-related increases in ΔCK and ΔAST; however, <10% of all subjects experienced a Grade ≥3 shift from baseline in CK or AST concentrations. Conclusions: ASP2215 has demonstrated exposure-related FLT3 inhibition and a pharmacokinetic profile that support once-daily oral administration for the treatment of AML in subjects who relapsed after, or are refractory to, induction or salvage treatment. Table. ASP2215 Pharmacokinetic Parameters after Multiple-Dose Administration 20 mg (n=4) 40 mg (n=3) 80 mg (n=3) 120 mg (n=3) 200 mg (n=2) 300 mg (n=3) 450 mg (n=3) Cmax(ng/mL) 45.6 (30.5, 137) 106 (76.7, 140) 396 (217, 516) 282 (248, 593) 1460 (886, 2040) 1260 (1040, 2280) 1150 (776, 1530) Tmax(hr) 4.01 (4.00, 6.00) 3.87 (0.500, 6.00) 4.33 (4.00, 4.42) 2.02 (1.95, 5.75) 6.03 (6.00, 6.07) 6.05 (4.08, 6.07) 5.00 (4.07, 5.93) AUC0-24(ng·h/mL) 926 (543, 2480) 2460 (1750, 2800) 6280 (4160, 10600) 6190 (4200, 11300) 31500 (16500, 46600) 28700 (22300, 43300) 11500 (8070, 14900) t1/2 (hr) 52.8 (39.7, 83.1) 83.7 (68.5, 243) 91.5 (60.9, 108) 45.3 (30.5, 63.3) 143 (99.7, 186) 159 (83.3, 187) 56.9 (51.5, 62.3) Rac 3.70 (2.92, 5.51) 5.55 (4.64, 15.1) 6.02 (4.18, 7.02) 3.25 (2.38, 4.33) 9.08 (6.51, 11.7) 10.1 (5.53, 11.7) 3.94 (3.62, 4.27) Data are presented as median (minimum, maximum). AUC0-24, area under the concentration-time curve between 0-24 hr; Cmax, maximal concentration; t1/2, elimination half-life; Tmax, time to maximal concentration; Rac, accumulation ratio. Disclosures Smith: Astellas: Research Funding; Plexxikon: Research Funding. Off Label Use: ASP2215 is an investigational product for the treatment of AML. Perl:Astellas US Pharma Inc.: Consultancy; Ambit/Daichi Sankyo: Consultancy; Arog Pharmaceuticals: Consultancy; Asana Biosciences: Consultancy; Actinium Pharmaceuticals: Consultancy. Altman:Novartis: Other: Advisory board; BMS: Other: Advisory board; Seattle Genetics: Other: Advisory board; Spectrum: Other: Advisory board; Ariad: Other: Advisory board; Astellas: Other: Advisory board; assistance with abstract preparation. Gill:Astellas Pharma US, Inc: Employment. Kadokura:Astellas Pharma Global Development: Employment, Other: Personal fees. Yuen:Astellas Pharma, Inc.: Employment. Fisniku:Astellas: Employment. Liu:Astellas: Employment. Nagase:Astellas: Employment. Sargent:Astellas Pharma US, Inc: Employment. Bahceci:Astellas Pharma Global Development: Employment.
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Min, Yoo-Hong, Hyeoung Joon Kim, Kyoo Hyung Lee, Sung-Soo Yoon, Jae Hoon Lee, Hee-Sook Park, Jin Seok Kim, et al. "A Multi-Center, Open Label Study Evaluating the Efficacy of Iron Chelation Therapy with Deferasirox in Transfusional Iron Overload Patients with Myelodysplastic Syndromes or Aplastic Anemia Using Quantitative R2 MRI." Blood 112, no. 11 (November 16, 2008): 3649. http://dx.doi.org/10.1182/blood.v112.11.3649.3649.
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Abstract Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a median of 30 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (10.3%), 20 (69.0%), and 4 cases (13.8%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64%) were severe form. Mean value of serum ferritin level in enrolled patients was 4,417 ± 3,378 (4,788 ± 3,996 in MDS, 4,185 ± 2,962 in AA) ng/ml at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 23.9 ± 13.8 (26.1 ± 15.0 in MDS, 22.8 ± 13.2 in AA) mg Fe/g dry weight. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p<0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. A consistent decrease in the serum ferritin level was demonstrated during the first 6 months in vast majority of patients despite of continued transfusion (209.7 ± 159.9 ng/ml and 324.0 ± 289.4 ng/ml per month in MDS and AA, respectively). Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 6 months of medication, a slower decrease in the serum ferritin level was observed in MDS patients. In 30 cases, one-year medication of deferasirox was completed. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,085 ± 2,150 ng/ml (64.4% of baseline level) and 2,913 ± 2,232 ng/ml (69.6% of baseline level, p<0.01) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 24 cases, and LIC was significantly decreased to the level of 19.3 ± 13.6 mg Fe/g dry weight (67.4% of baseline value, p=0.01). Decrease in the level of LIC at EOS in MDS (64.3% of baseline) was comparable to that in AA cases (68.5% of baseline). The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 28 (35.4%) cases because of death (7 in MDS and 6 in AA), patient refusal (11 cases), and decrease in the serum ferritin level below 500ng/ml (4 cases). All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient’s transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients.
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Baron, Frederic, E. Willems, E. Baudoux, N. Wanten, M. T. Closon, N. Witvrouw, K. Hafraoui, P. Frere, Georges Fillet, and Yves Beguin. "Low-Dose Total Body Irradiation (TBI) Followed by Donor Lymphocyte Infusion Increases Donor T-Cell Chimerism Levels in Patients with Low Donor T-Cell Chimerism after Nonmyeloablative Conditioning." Blood 108, no. 11 (November 16, 2006): 2961. http://dx.doi.org/10.1182/blood.v108.11.2961.2961.
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Abstract Background. Low donor T-cell chimerism levels after allogeneic hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning have been associated with high risks of both graft rejection and relapse/progression (Baron et al., Blood2004, vol 104, p2254 and Baron et al., J Clin Oncol2005, vol 23, p1993). In a preclinical canine model, DLI preceded by 2 Gy TBI converted mixed to full donor chimerism after nonmyeloablative conditioning (Taranova et al., Blood2003, vol 102, 256a). Here, we investigated the ability of donor lymphocyte infusion (DLI) preceeded (n=15; TBI/DLI group) or not (n=15; DLI (“historical”) group) by 2 Gy TBI (given a few hours before DLI) to increase donor T-cell chimerism levels in patients with low donor T-cell chimerism levels after HCT. Methods. Conditioning regimen for HCT consisted of 2 Gy TBI with (n=15) or without (n=11) added fludarabine. 20 patients received PBSC from related, and 6 PBSC from HLA-matched unrelated donors. Peripheral blood stem cells (PBSC) were unmanipulated in 15 patients, and CD8-depleted in the 11 remaining patients. Indication for TBI/DLI included < 50% donor T-cell chimerism or decrement of donor T-cell chimerism by 20% (or 10% if below 60%). Depending of patient-donor relationship, DLIs were given at a dose of 1 to 10 × 107 T-cells/kg (median 2 × 107 T-cells/kg), 42 to 725 days (median 68.5 days) following HCT. Prophylactic postgrafting immunosuppression was pursued after DLI in all but one patients. Results. Before DLI, donor T-cell chimerism levels ranged from 15 to 77% (median 44%) in the DLI group, versus from 24 to 66% (median 47%) in the TBI/DLI group (P=0.66). Two months after DLI, donor T-cell chimerism levels ranged from 15 to 93% (median 53%) in the DLI group (P=0.10 in comparison to before DLI), versus from 20 to 98% (median 56%) in the TBI/DLI group (P=0.04 in comparison to before DLI) (Figure 1). In addition, 0 of 15 patients in the DLI group versus 5 of 15 patients in the TBI/DLI group had > 25% increased T-cell chimerism levels 2 months after DLI (P=0.04). Highest T-cell chimerism levels after DLI ranged from 15 to 99% (median 71%) in the DLI group, versus from 43 to 100% (median 96%) in the TBI/DLI group (P=0.06). Further, 2 of 15 patients in the DLI group, versus 0 of 15 patients in the TBI/DLI group experienced graft rejection. In the DLI group, 3 patients developed grade II–IV acute GVHD (2 grade II and 1 grade IV), while 1 patient in the TBI/DLI group experienced grade II acute GVHD. TBI/DLI was followed by grade IV hematologic toxicities in most patients, but most of them remained treated in the outpatient clinic. One-year overall survival was 67% in the DLI group versus 73% in the TBI/DLI group (NS). Conclusions. DLI increased donor T-cell chimerism levels in a number of patients when preceeded by low dose TBI. However, hematological toxicity of TBI/DLI was relatively high, with most patients requiring several RBC and Plt transfusions. Further studies are needed to assess its impact on HCT outcomes. Figure Figure
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Quarmyne, Maa-Ohui, Janet Figueroa, Courtney McCracken, Charles T. Quinn, Clark Brown, and Clinton H. Joiner. "Effect of Acute Transfusion on Cerebral Oxygenation in Patients with Sickle Cell Disease." Blood 130, Suppl_1 (December 7, 2017): 988. http://dx.doi.org/10.1182/blood.v130.suppl_1.988.988.
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Abstract Introduction : The molecular abnormality in sickle hemoglobin (HbS) produces a unique cellular pathology characterized by fragile and rigid red blood cells which block the microcirculation, which, in concert with large vessel vasculopathy and the anemia of sickle cell disease (SCD), compromises oxygen delivery to the brain and other organs. Long-term, periodic transfusions are commonly used to prevent and ameliorate neurologic complications related to vasculopathy, particularly stroke. Despite widespread use of transfusions, little is known about the physiological effects on cerebral O2 delivery, which represents an integration of multiple, potentially opposing processes. While increased hematocrit improves O2 carrying capacity, the consequent elevation of blood viscosity has the potential to impede blood flow to cerebral tissue. Also, 2,3-BPG levels in stored blood are depleted, temporarily impairing O2 delivery. Advances in cerebral oximetry (using near infrared spectroscopy) provide an opportunity to address these issues directly to study cerebral oxygenation following transfusions in SCD. The FORE-SIGHT© cerebral oximeter (CAS Medical Systems) measures cerebral tissue hemoglobin saturation (SCTO2), a mixture of arterial and venous oxygen saturation (30:70) in a voxel of tissue near the gray-white junction in the frontal lobes. Using measured arterial Hb saturation (SaO2) by peripheral pulse oximetry and SCTO2 by cerebral oximetry, cerebral venous Hb saturation (SvO2) can be derived. Additionally, using a measured HbO2 affinity curve derived at the time of SCTO2 determination, SvO2 can be converted to venous oxygen tension, PvO2. PvO2 is in dynamic equilibrium with tissue oxygen tension and represents the best estimate of tissue oxygenation. The primary objective of this study was to use cerebral oximetry to assess and monitor cerebral tissue oxygenation following an elective pre-operative RBC transfusion. Methods : This pilot prospective cohort study enrolled 12 patients with sickle cell anemia (SS, Sb0 thalassemia) in steady-state, who had elective, pre-operative transfusions. Patients who had received transfusion within 3 months or had known cerebral vasculopathy were excluded. Nine patients completed the planned 3 months of study follow up. Two patients were taken off study within a week of enrollment because of difficulties with cerebral oximetry measurements. One did not follow-up after 2 months of participation. Each patient had measurements of SCTO2 prior to the initiation of transfusion, continuously during transfusion, and at predetermined times points post-transfusion, for up to 3 months. Other parameters related to cerebral Hb oxygenation were also measured, including Hb, HbA, HbF, HbS, P50 and 2,3-BPG. The relationship between cerebral oxygenation with age and other predictors of oxygenation was assessed using linear mixed models. The first two post-transfusion measurements (within 96 hours) were compared against pre-transfusion measurements using Wilcoxon signed-rank tests. Results : SCTO2 was significantly associated with age (p=0.02), Hb (p=0.01) and HbA % (p=0.03 (Table 1). Immediately post-transfusion, SCTO2, increased from median values of 58% to 68.5%, p 0.004 (Table 2). Arterial saturation (SaO2) was unchanged post-transfusion, thus the increase in SCTO2 resulted in an increased (calculated) venous saturation (SvO2). P50 fell post transfusion, as expected, and despite increased SvO2, PvO2 remained unchanged. Arterial and venous oxygen content (CaO2, CvO2) increased post transfusion as expected because Hb and SvO2 increased. However, the difference in arterial and venous oxygen content (CdO2 = CaO2 - CvO2) remained unchanged after transfusion. Similar trends in these parameters were observed in second measurements made up to 96 hours after transfusion (Table 2). Since oxygen delivery equals CdO2 × blood flow, cerebral oxygen delivery would only increase if blood flow were increased by transfusion, contrary to reports {Neurology. 1989 Mar;39(3):344-8; Stroke 25:2153-8, 1994}. Conclusion: Although cerebral hemoglobin oxygen saturation (SCTO2) increased after acute transfusion, calculated tissue oxygen tension (PvO2) and apparent oxygen delivery (CdO2) remained unchanged, providing no evidence for acute improvement in cerebral oxygenation after transfusion in SCD. Disclosures Quinn: Global Blood Therapeutics: Research Funding.
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Chari, Ajai, Soe-Soe Win, Sharon Tindle, and Sundar Jagannath. "Outcomes of Plasma Cell Disorder Patients with Abnormal Hepatitis B and C Screening Tests Prior to Autologous Stem Cell Harvest and Transplantation." Blood 118, no. 21 (November 18, 2011): 4472. http://dx.doi.org/10.1182/blood.v118.21.4472.4472.
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Abstract Abstract 4472 Background: High dose melphalan with autologous stem cell transplant (ASCT) is a standard treatment for patients with multiple myeloma (MM) and AL amyloidosis. A standard part of the pre stem cell harvest (SCH)/SCT evaluation at most medical centers is a battery of infection screening tests. While the reactivation of hepatitis B with rituximab is well described, there are limited data on the outcomes or significance of abnormal test results in non-endemic areas in the context of ASCT. Moreover, it is unclear whether patients with plasma cell disorders (PCDs), with their dysregulation of humoral immunity, may have differing rates of abnormal test results on antibody based testing than patients without PCDs. Indeed, one study found hepatitis B seroconversions more commonly with MM post ASCT (Uhm et al, ASBMT 2007). We therefore conducted this retrospective study to examine the outcomes of abnormal infection screening in patients with PCDs and non PCDs undergoing SCH/SCT in the New York Metropolitan area. Method: We reviewed 639 consecutive patients who had autologous hematopoietic stem cell harvests (SCH) done at Saint Vincent Hospital, NY from February, 2000 to March, 2010. Of these patients, 555 had PCDs including multiple myeloma and AL Amyloidosis. The 84 non PCDs included lymphoma and solid tumors patients were used as a comparator group. Result: We first reviewed the rate of positive infectious screening tests and found no difference between PCDs (55 out of 555, 9.9%) and non PCDs (9 out of 84, 10.7%). Of these patients with abnormal screening results, 40 and 7 patients respectively went on to ASCT. 11 patients had more than one infection screening test abnormality, making a total of 76 abnormal tests. As shown in Table 1, 67.1% (51/76) were positive for Hep B core Ab, 19.7% (15/76) for Hepatitis C Ab, 6.5 % (5/76) for syphilis, 5.2 % (4/76) for HTLV and 1.3% (1/76) for HIV. Amongst the 44 patients with PCDs and positive anti-HBc total, 39% (17) were positive antiHBc Ig G antibody but negative for IgM, representing chronic carriers. 9% (4) were negative by both antiHBc Ig M and IgG, which may represent false positive tests, and this pattern was not seen in any of the 7 patients with non PCDs. Of the PCD patients who had Hepatitis B PCR testing, 1 showed chronic active hepatitis and 9 had undetectable viral load. 68.5% of positive Hepatitis B screening patient went on to SCT (including the patient with PCR + but IgM was negative) regardless of the status of test results without any treatment for hepatitis B. Of the 13 PCD patients with positive anti-HCV Ab screening, 46% (6) had active viral replication by PCR and 30% (4) had with undetectable viral load by PCR. 2 patients had negative repeat HCV testing. Only one patient with chronic active HCV infection (146,1200,000 IU/ml) by PCR got treatment by IFN and Ribavirin pretransplant and did not get ASCT. 66.6% of positive Hepatitis C screening patient went on to SCT. Five patients had RBC transfusions during the year preceding infection screening (3 with positive antiHBc total antibody, 1 with HCV antibody and 1 with HTLV antibody). One patient had IVIG transfusion 7 days before screening. There appeared to be no relationship to abnormal screening tests and MM subtype or hypogammaglobulinemia. Of those patients who went on to SCT, transient grade 1 transaminitis during transplant or by day 100 was found in 4 patients (6%) with positive hepatitis B screening. One patient had transient asymptomatic hepatomegaly. We observed no serious hepatic complications in chronic hepatitis B and C carriers without active disease and ASCT appears to be feasible and safe without any anti-viral treatment. Conclusion With the exception of a possible excess of false positive hepatitis B testing in patients with PCDs, there are no other differences in rates of abnormal infection screening tests between PCDs and nonPCDs. The use of more specific viral testing like PCR and Western blot or highly sensitive immunoassay should be considered to avoid false positive results in the analysis of antibody based tests to avoid both unnecessary delays of SCT and anti-viral treatment. In the absence of clinical hepatitis and active viral replication, treatment for chronic Hepatitis B and C carriers does not appear to be required preASCT. Disclosures: Jagannath: Celgene: Membership on an entity’s Board of Directors or advisory committees; Merck: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees.
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Pho, Nguyen Van, Pham Tich Xuan, and Pham Thanh Dang. "Occurrence of supergene nickel ores in the Ha Tri Massive, Hoa An District, Cao Bang Province." VIETNAM JOURNAL OF EARTH SCIENCES 40, no. 2 (January 19, 2018): 154–65. http://dx.doi.org/10.15625/0866-7187/40/2/11676.
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Nickel (Ni) laterites are regolith materials derived from ultramafic rocks and play an important role in the world's Ni production. Ni-laterite deposits are the supergene enrichment of Ni formed from the intense chemical and mechanical weathering of ultramafic parental rocks. In Vietnam, the weathering profile containing Ni laterite was first discovered in the Ha Tri massive (Cao Bang). This profile develops on the Ha Tri serpentinized peridotite rocks classified to the Cao Bang mafic-ultramafic complex (North Vietnam) and exhibits thick weathered zone (10 - 15m). This work carried out a detailed study of the weathering profile at the center of Ha Tri massive. Samples from different horizons of the profile were collected and analyzed in detail by XRF, XRD and SEM-EDX methods to establish the relationship between the Ni-rich supergene products and the parental peridotites (lherzolite) rocks in Ha Tri massive. The results show that the saprolite horizon is most Ni-rich in the weathering profile in Ha Tri. In this horizon, Ni-silicate minerals of garnierite group such as pimelite, nepouite and other Mg-Ni silicates have been found. The appearance of minerals of garnierite group is due to the exchange of Mg by Ni during weathering of peridotite minerals, especially olivine, which leads to the enrichment of the supergene Ni. The occurrence of Ni silicates suggests the existence of the supergene Ni ore in the weathering profile of the Ha Tri massive.References Bosio N.J., Hurst J.V., Smith R.L., 1975. Nickelliferousnontronite, a 15 Å garnierite, at Niquelandia, Goias Brazil. Clays Clay Miner., 23, 400-403. Brand N.W., Butt C.R.M., Elias M., 1998. Nickel Laterites: Classification and features. AGSO Journal of Australian Geology & Geophysics, 17(4), 81-88. Bricker O.P., Nesbitt H.W. and Gunter W.D., 1973. The stability of talc. American Mineralogist, 58, 64-72. Brindley G.W. and Hang P.T., 1973. The nature of garnierites. Structures, chemical composition and color characteristics. Clay and Clay Minerals, 21, 27-40. Brindley G.W. and Maksimovic Z., 1974. The nature and nomenclature of hydrous nickel-containing silicates. Clay Minerals, 10, 271-277. Brindley G.W. and Wan H.M., 1975. Composition structures and thermal behavior of nickel containing minerals in thelizardite-ne´pouite series. American Mineralogist, 60, 863-871. Brindley G.W., Bish D.L. and Wan H.M., 1979. Compositions, structures and properties of nickel containing minerals in the kerolite-pimelite series. American Mineralogist, 64, 615-625. Cluzel D. and Vigier B., 2008. Syntectonic mobility of supergene nickel ores from New Caledonia (Southwest Pacific). Evidence from faulted regolith and garnierite veins. Resource Geology, 58, 161-170. Colin F., Nahon D., Trescases J.J., Melfi A.J., 1990. Lateritic weathering of pyroxenites at Niquelandia, Goais, Brazil: The supergene behavior ofnickel: Economic Geology, 85, 1010-1023. Das S.K., Sahoo R.K., Muralidhar J., Nayak B.K., 1999. Mineralogy and geochemistry of profilesthrough lateritic nickel deposits at Kansa,Sukinda, Orissa. Joural of Geoogical. SocietyIndia, 53, 649-668. Decarreau A., Colin F., Herbillon A., Manceau A., Nahon D., Paquet H., Trauth-Badaud D.,Trescases J.J., 1987. Domain segregation in NiFe-Mg-Smectites. Clay Minerals, 35, 1-10. Freyssinet P., Butt C.R.M. and Morris R.C., 2005. Oreforming processes related to lateritic weathering. Economic Geology, 100th aniversary volume, 681-722.Garnier J., Quantin C., Martins E.S., Becquer T., 2006. Solid speciation and availability of chromium in ultramafic soils from Niquelandia, Brazil. Journal of Geochemical Exploration, 88, 206-209. Garnier J., Quantin C., Guimarães E., Becquer T., 2008. Can chromite weathering be a source of Cr in soils? Mineralogy Magazine, 72, 49-53. Gleeson S.A., Butt C.R. and Elias M., 2003. Nickel laterites: A review. SEG Newsletter, 54, 11-18. Gleeson S.A., Butt C.R., Wlias M., 2003. Nickellaterites: a review. SEG Newsletter, Society of Economic Geology, 54. Available from www.segweb.org. Golightly J.P., 1981. Nickeliferous laterite deposits. Economic Geology, 75th Anniversary volume, 710-735. Golightly J.P., 2010. Progress in understanding the evolution of nickel laterite. Society of Economic Geology, In Special Publication, 15, 451-485. Manceau A. and Calas G., 1985. Heterogeneous distribution of nickel in hydrous silicates from New Caledonia ore deposits. American Mineralogist, 70, 549-558. Nguyen Van Pho, 2013. Tropic weathering in Vietnam (in Vietnamese). Pubisher Science and Technology, 365p.Ngo Xuan Thanh, Tran Thanh Hai, Nguyen Hoang, Vu Quang Lan, S. Kwon, Tetsumaru Itaya, M. Santosh, 2014. Backarc mafic-ultramafic magmatism in Northeastern Vietnam and its regional tectonic significance. Journal of Asian Earth Sciences, 90, 45-60.Pelletier B., 1983. Localisation du nickel dans les minerais ‘‘garnieritiques’’ de Nouvelle-Caledonie. Sciences Ge´ologique: Me´moires, 73, 173-183.Pelletier B., 1996. Serpentines in nickel silicate ores from New Caledonia. In Grimsey E.J., and Neuss I. (eds): Nickel ’96, Australasian Institute of Miningand Metallurgy, Melbourne, Publication Series 6(9), 197-205. Proenza J.A., Lewis J.F., Galı´ S., Tauler E., Labrador M., Melgarejo J.C., Longo F. and Bloise G., 2008. Garnierite mineralization from Falcondo Ni-laterite deposit (Dominican Republic). Macla, 9, 197-198. Soler J.M., Cama J., Galı´ S., Mele´ndez W., Ramı´rez, A., andEstanga, J., 2008. Composition and dissolution kinetics ofgarnierite from the Loma de Hierro Ni-laterite deposit,Venezuela. Chemical Geology, 249, 191-202. Springer G., 1974. Compositional and structural variations ingarnierites. The Canadian Mineralogist, 12, 381-388. Springer G., 1976. Falcondoite, nickel analogue of sepiolite. The Canadian Mineralogist, 14, 407-409.Svetlitskaya T.V., Tolstykh N.D., Izokh A.E., Phuong Ngo Thi, 2015. PGE geochemical constraints on the origin of the Ni-Cu-PGE sulfide mineralization in the Suoi Cun intrusion, Cao Bang province, Northeastern Vietnam. Miner Petrol, 109, 161-180.Tran Trong Hoa, Izokh A.E., Polyakov G.V., Borisenko A.S., Tran Tuan Anh, Balykin P.A., Ngo Thi Phuong, Rudnev S.N., Vu Van Van, Bui An Nien, 2008. Permo-Triassic magmatism and metallogeny of Northern Vietnam in relation to the Emeishan plume. Russ. Geol. Geophys., 49, 480-491.Trescases J.J., 1975. L'évolution supergene des roches ultrabasiques en zone tropicale: Formation de gisements nikelifères de Nouvelle Caledonie. Editions ORSTOM, Paris, 259p.Tri T.V., Khuc V. (eds), 2011. Geology and Earth Resources of Vietnam. Publishing House for Science and Technology, 645p (in English). Villanova-de-Benavent C., Proenza J.A., GalíS., Tauler E., Lewis J.F. and Longo F., 2011. Talc- and serpentine-like ‘‘garnierites’’ in the Falcondo Ni-laterite deposit, Dominican Republic. ‘Let’s talk ore deposits’, 11th Biennial Meeting SGA 2011, Antofagasta, Chile, 3p.Wells M.A., 2003. Goronickel laterite deposit. New Caledonia. CRC LEME, p.3.
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Castón Boyer, Pedro. ""Los orígenes de la intervención estatal en los problemas sociales" (Recensión)." Revista de Fomento Social, September 30, 2000, 473–76. http://dx.doi.org/10.32418/rfs.2000.219.2492.
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González Portillo, Auxiliadora. ""VII Informe sobre exclusión y desarrollo social en España"." Revista de Fomento Social, June 30, 2015, 133–36. http://dx.doi.org/10.32418/rfs.2015.277.1652.
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Tomás, Jean-Luc, Maria Ianeva, Pascal Simonet, and Yves Clot. "Activité et vision professionnelle." Revue d'anthropologie des connaissances 14, no. 3 (September 1, 2020). http://dx.doi.org/10.4000/rac.6814.
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Yue, Wen-Wen, Shu-Rong Wang, Feng Lu, Xiao-Long Li, Hui-Xiong Xu, Li-Ping Sun, Le-Hang Guo, Ya-Ping He, Dan Wang, and Zhi-Qiang Yin. "Quality of Life and Cost-Effectiveness of Radiofrequency Ablation versus Open Surgery for Benign Thyroid Nodules: a retrospective cohort study." Scientific Reports 6, no. 1 (November 24, 2016). http://dx.doi.org/10.1038/srep37838.
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Abstract This study is to compare the health-related quality of life (HRQoL) and cost-effectiveness of radiofrequency ablation (RFA) and open thyroidectomy (OT) for benign thyroid nodules (BTNs) treatment. HRQoL and utility were assessed for 404 BTN patients immediately before treatments (RFA:OT = 137:267) and at 6-month visit. A cost-effectiveness analysis was performed from societal perspective in the China context. Resource use (hospitalization, sick leaves) was collected. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for RFA and OT. Sensitivity analyses of costs of RFA were performed. At 6-month visit, patients treated with RFA had significantly better HRQoL than patients treated with OT on general health (68.5 versus 66.7, P = 0.029), vitality (71.3 versus 67.5, P < 0.001) and mental health (80.9 versus 79.3, P = 0.038). RFA was more effective than OT in terms of quality-adjusted life-years (QALYs; 0.01QALY/patient) but more expensive (US$823/patient). The probability that RFA would be cost effective at a US$50,000/QALY threshold was 15.5% in China, and it would be increased to 88.4% when price of the RFA device was lowered by 30%. RFA exhibited a significant improvement of HRQoL relative to OT, but is unlikely to be cost effective at its current price in short time.
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Assmus, Mark A., D. Beyer, Joan Hanks, Mathew Estey, Keith F. Rourke, Trevor Schuler, and Tim Wollin. "Quality and cost assessment of Canadian Urological Association microscopic hematuria guidelines in clinical practice: Turning urine into gold." Canadian Urological Association Journal 13, no. 10 (January 14, 2019). http://dx.doi.org/10.5489/cuaj.5809.
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Introduction: Asymptomatic microscopic hematuria (AMH) is defined in the Canadian Urological Association (CUA) guidelines as >2 red blood cells (RBCs) per high-powered field (hpf). Our objective is to evaluate guideline adherence for AMH at our centre. Secondarily, we aim to identify areas of the guideline that can be optimized.
Methods: We retrospectively reviewed 875 consecutive adults referred to two urologists for hematuria from June 2010–2016. Patient characteristics, risk factors, and outcomes were added to an encrypted REDCap database. Evaluation of microscopic hematuria reporting was performed by analyzing 681 urine samples reported as 1–5 RBC/hpf. Healthcare costs were obtained from Alberta Health Services (AHS), Data Integration and Management Repository (DIMR), and Alberta Society of Radiologists (ASR).
Results: Of the 875 patients referred with hematuria, 400 had AMH. Overall, 96.5% completed evaluation consistent with the CUA guideline. The incidence of pathology requiring surgical intervention was 21/400 (5%), with a 0.8% rate (3/400) of urothelial cell carcinoma (UCC) (non-invasive, low-grade). No malignancy was found in non-smokers with normal cytology, normal imaging and <50 RBC/hpf; 44% had AMH in the 1–5 RBCs/hpf range. Only 41% (279/681) of urine samples categorized as 1–5 RBCs/hpf had guideline-defined microscopic hematuria. By changing local microscopic hematuria reporting to differentiate 1–2 and 3–5 RBCs/hpf, we estimate $745 000 in annual savings.
Conclusions: At our centre, CUA AMH guideline adherence is high. We did not find malignancy in non-smokers with normal cytology, imaging, and <50 RBC/hpf. We identified and changed regional microscopic hematuria reporting to fit the CUA definition, eliminating unnecessary investigations and healthcare costs.
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Damante, Mark A., Kristin Huntoon, Thomas Olencki, and Bradley Elder. "Survival Benefit With Resection of Brain Metastases From Renal Cell Carcinoma in the Setting of Molecular Targeted Therapy and Immune Therapy." Neurosurgery 66, Supplement_1 (August 20, 2019). http://dx.doi.org/10.1093/neuros/nyz310_219.
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Abstract INTRODUCTION Patient survival with renal cell carcinoma (RCC) has improved with the use of molecular targeted agents and immunotherapy. Given the potential activity of these agents in treating brain metastases (BM), the role of aggressive local management with surgery and/or radiation may diminish. This study evaluated the benefit of aggressive local therapy of RCC BM in the setting of molecular targeted agents and/or immunotherapy. METHODS A retrospective single-center review between 2011 and 2018 identified 1659 patients treated for RCC. The study group included patients that developed BM and received molecular targeted agents and/or immunotherapy during the course of their disease. Data analyzed included demographic information, systemic treatments, and local BM treatment modalities. Kaplan-Meier curves and log-rank values were used to assess progression free survival (PFS) and overall survival (OS) following RCC and BM diagnosis. RESULTS Of 1659 patients, 108 (6.5%) were diagnosed with BM during their clinical course. Mean OS from diagnosis of RCC for these 108 patients was 44.5 ± 40.1 mo, with 1-, 3-, and 5-yr survival of 76.9%, 43.3%, and 38.1%. All patients were treated with molecular targeted agents and/or immunotherapy. OS was analyzed based on three treatment groups: systemic therapy only (26.1 ± 31.2, n = 21), systemic and radiotherapy (41.4 ± 34.9, n = 54), and systemic and radiotherapy plus BM resection (61.4 ± 46.9, n = 33). Survival benefit was seen with surgery compared to systemic therapy alone (P = .002) and the systemic and radiotherapy cohort (P = .038). PFS did not differ significantly between cohorts. Variables such as pre-treatment performance status (ECOG P = .085; KPS P = .231), number of BM (median 2, P = .685) and status of systemic disease at the time of BM diagnosis did not differ significantly. CONCLUSION In the setting of molecular targeted agents and immunotherapy, BM resection maximizes OS in surgical candidates. Prospective clinical trials are needed to elucidate activity of newer molecular targeted agents and immunotherapy in RCC BM treatment.
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Camacho Laraña, Ildefonso, José Juan Romero Rodríguez, Araceli De los Ríos Berjillos, Adolfo Rodero Franganillo, and Pedro Pablo Pérez Hernández. "Reseñas." Revista de Fomento Social, June 30, 2004, 467–84. http://dx.doi.org/10.32418/rfs.2004.234.2326.
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Reseñas de la obra de:
GARCÍA MARZÁ, D., (2004), Ética empresarial. Del diálogo a la confianza, Madrid, Ed. Trotta, 290 págs.
BELLO, W., (2004), Desglobalización. Ideas para una nueva economía mundial. Barcelona, Ed. Icaria e Intermón Oxfam, 148 páginas.
Economistas. España 2003. Un balance, nº 100 extra, año 22, 411 págs.
VV.AA. (2003), “La economía española en el período constitucional”, número monográfico de Información Comercial Española, nº 811, diciembre 2003, Madrid, Edita Secretaría de Estado de Comercio y Turismo del Ministerio de Economía, 372 páginas.
VV.AA., (2003), “Las balanzas fiscales en España”, Papeles de Economía Española, nº 99, 256 págs.
NAVARRO GARCÍA, J.R. (Coord.), (2004), Municipios y administración: estudios sobre cooperación con América Latina, Sevilla, Ed. Escuela de Estudios Hispano–Americanos y Ayuntamiento de Sevilla, 218 págs.
INGCO, M. D. y NASH, J. D. (Eds.), (2004), Agriculture and the WTO. Creating a Trading System for Development, Washington, Ed. World Bank and Oxford University Press, 387 págs.
VV. AA. (2003), “Sector agroalimentario. PAC y cambios en la demanda”, número monográfico de Papeles de Economía Español, nº 96, Madrid, Edita Fundación de las Cajas de ahorro confederadas para la investigación económica y social (FUNCAS), 235 páginas.
MINISTERIO DE AGRICULTURA, PESCA Y ALIMENTACIÓN, (2003), Libro blanco de la agricultura y el desarrollo rural, Madrid, Ed. Ministerio de Agricultura, Pesca y Alimentación, 4 volúmenes (48+733+685+845 páginas).
ROMERO, J.J. Y FERRERO, G. (Edit.), (2004), Desarrollo rural en Nicaragua. Del consenso en los principios a una propuesta para la acción. Bilbao, Ed. Desclée de Brouwer, Colección ETEA, 247 págs.
FUNDACIÓN SEMINARIO DE INVESTIGACIÓN PARA LA PAZ, (Eds.), (2004), El pulso de América Latina, Zaragoza, Ed. Departamento de Educación, Cultura y Deporte, Gobierno de Aragón, 525 págs.
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Alresayes, Saad, Sameer A. Mokeem, Aasem M. Alhenaki, Fahim Vohra, and Tariq Abduljabbar. "Evaluation of the implant diameter on the initial-stability of narrow- and standard-diameter implants placed in simulated Type-I and Type-IV bone-blocks." Pakistan Journal of Medical Sciences 37, no. 3 (February 24, 2021). http://dx.doi.org/10.12669/pjms.37.3.3943.
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Objective: A comparison of the initial stability of narrow- and standard-diameter implants (SDIs) placed in Type-I and Type-IV bone-blocks is not yet reported. The aim was to evaluate in-vitro the influence of implant diameter on the initial stability of narrow- and standard-diameter implants (SDIs) placed in simulated Type-I and Type-IV bone-blocks.
Methods: The present experimental in-vitro study was performed between July and September 2020 at the Specialist Dental Practice, Riyadh, Saudi Arabia. Narrow- and standard-diameter implants were placed 3-mm apart in simulated soft (Type-IV) and dense (Type-I) bone blocks by a trained and calibrated investigator. In groups A (Type-IV bone blocks) and B (Type-I bone blocks), implants were inserted using an insertion-torque and drilling-speed of 15-30 Ncm and 1000-1500 rpm, respectively with the implant collar at the crest of simulated bone blocks. In all samples, initial-stability was recorded using resonance frequency analysis (RFA). Sample-size estimation was done and group-comparisons were carried out. A P-value of 0.01 or less reflected statistical significance.
Results: In Groups-A and -B, 44 (22 NDIs and 22 SDIs) and 44 (22 NDIs and 22 SDIs) were placed. In group-A, the mean RFA values for NDIs and SDIs were 68.5 ± 3.5 and 69.1 ± 2.4, respectively. In Group-B, the mean RFA values for NDIs and SDIs were 78.06 ± 9.6 and 75.3 ± 5.2. RFA values among NDIs and SDIs in groups A and B were similar.
Conclusion: The NDIs and SDIs show comparable initial-stability when positioned in simulated Type-I and Type-IV bone blocks.
doi: https://doi.org/10.12669/pjms.37.3.3943
How to cite this:Alresayes S, Mokeem SA, Alhenaki AM, Vohra F, Abduljabbar T. Evaluation of the implant diameter on the initial-stability of narrow- and standard-diameter implants placed in simulated Type-I and Type-IV bone-blocks. Pak J Med Sci. 2021;37(3):---------. doi: https://doi.org/10.12669/pjms.37.3.3943
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Arabi, Ziad, Kaysi Saleh, Abdullah Hamad, and Mohammad Bukhari. "P1686MULTI-NATIONAL SURVEY AMONG NEPHROLOGISTS AND TRANSPLANT SURGEONS ABOUT THE SUITABILITY AND ACCEPTANCE OF MARGINAL LIVE KIDNEY DONORS WITH MICROSCOPIC HEMATURIA." Nephrology Dialysis Transplantation 35, Supplement_3 (June 1, 2020). http://dx.doi.org/10.1093/ndt/gfaa142.p1686.
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Abstract Background and Aims Potential kidney donors with isolated hematuria are often excluded from donating although there is a wide controversy about the definition and threshold of investigations or exclusion form donation. Many centers use the cut off of > 3 RBC in men and > 5 RBC in women. Some centers consider positive dipstick on urinalysis as the definition of microscopic hematuria. Kidney biopsy in these donors can be borderline and inconclusive. We conducted a short survey about the suitability of these marginal living kidney donors with microscopic hematuria. Method This is a cross-sectional survey of nephrologists and transplant surgeons (TS) about suitability and acceptance of marginal live kidney donors with isolated microscopic hematuria. The question was about a 35-yr. old man non-smoker with isolated microscopic hematuria (4 RBC on repeated UA and trace hematuria on dipstick) and negative imaging. The survey was mainly distributed through American Society of Transplantation, American Society of Transplant Surgeons and European Renal Association-European Dialysis and Transplant Association. In-training nephrologists or transplant surgeons were excluded. Results A total of (n= 122 from 22 countries, 80% nephrologists and 20% TS) responded to the survey. Most respondents were experienced in donor evaluation (72% of physicians have over 6 years’ experience and 68.5% of them perform donors’ evaluation on weekly or monthly bases). Interestingly, at this low level of microscopic hematuria (4 RBC on repeated UA and trace hematuria on dipstick) only very limited number of respondents (7.5%) would allow donation without further work up. Instead, most respondents (n= 75, 63%) would ask for kidney biopsy prior to taking further steps. Many physicians (n=35, 29%) choose to ask for an alternative donor to avoid the hassle of kidney biopsy which may not change the management. There was no difference in acceptance rate for donors between TS and nephrologists (7.2% versus 8.3% respectively, p=NS), requesting kidney biopsy (63.9% vs. 62.5%) or in declining these donors (28.8% versus 29.1%, p=NS). Conclusion Young kidney donors with persistent isolated microscopic hematuria (even at mild degree) require further evaluation with kidney biopsy before donation. However up to one third of the nephrologist and transplant surgeon will ask for an alternative donor to avoid the hassle of kidney biopsy which can be borderline or inconclusive.
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Usenko, T. V., and V. G. Shulyak. "Вплив епоксиконазолу на гематологічні та цитохімічні показники периферичної крові щурів Wistar Hannover." Medical and Clinical Chemistry, no. 1 (May 3, 2018). http://dx.doi.org/10.11603/mcch.2410-681x.2018.v0.i1.8843.
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Introduction. Epoxiconazole is a highly effective triazole fungicide. It is a part of many modern compounds for the control of phytopathogens. Widely used in agriculture in all over the world and in Ukraine, in particular. Despite its hepatotoxic characteristics, this fungicide alters the hematological parameters of blood.The aim of the study – to investigate the effects of generic triazole fungicide epoxiconazole, 95% on hematological and cytochemical parameters of peripheral blood of Wistar Hannover rats in acute experiment.Research Methods. 10 healthy males of Wistar Han rats were equally divided into control (0 mg/kg/bw) and experimental groups. Dose 1580 mg/kg/bw of epoxiconazole (1/2 LD50) was administrated once orally by gavage to 5 experimental rats. Peripheral blood was studied at 0 and 1, 3, 7, 14 day after exposure (DAE). RBC, HGB, HCT, erytrocyte indices MCV, MCH, MCHC, WBC and PLT were, hemogram and morphological disturbances of cells were studied,percentage ratio of different types of leukocytes was calculated.The cytochemical status of leukocytes was assessed on the basis of determining the enzymatic activity of specific naphthol-AS-D-chloroacetateterase in neutrophils, succinate dehydrogenase and acid phosphatase in lymphocytes.Results and Discussion. Erythrocytosis in response to pesticide intoxication with a decrease of mean cellhemoglobin concentration in one erythrocyte; the reduction of hemoglobin concentration in the end of experiment against the background of active polychromasia confirmed the anemic effect of epoxiconazole. Reactive neutrophilia, stimulation of lymphocytopoiesis and monocytopoiesis, appearance of macrophages in the peripheral blood, increased activity of naphthol-AS-D-chloroacetateterase, succinate dehydrogenase and acid phosphatase were considered as compensatory mechanisms. Reverse quantitative changes in the ratio of lymphocytes subpopulations based on the activity of acid phosphatase were noted.Conclusions. Results of the study of generic fungicide epoxiconazole, 95% hematotoxic activity in the acute experiment on Wistar Hannover male rats showed the development of latent anemia, which was manifested in the late-term study; activation of monocytopoesis; increase of macrophages in the peripheral blood; changes in the immune response of the body and the appearance of atypical normocytes and lymphocytes with nuclear abnormalities.
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Ashouri, Rani, Abdullah S. Ahmad, Pradip Kamat, and Sylvain Dore. "Abstract WP412: Important Role of Scavenging Receptors on Hemoglobin-Injected Intracerebral Hemorrhage Model." Stroke 51, Suppl_1 (February 2020). http://dx.doi.org/10.1161/str.51.suppl_1.wp412.
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Introduction: Clinical and experimental studies have linked the presence of oxidative damage and neuroinflammation from free hemoglobin (Hb) to the innate immune response. CD36 has been identified as a macrophage/microglia surface receptor as part of a scavenging system, notably by RBC phagocytosis. CD163 is another surface receptor binding to Haptoglobin-Hb complexes with high affinity and Hb with lower affinity. These receptors participate in the clearance of extravasated erythrocytes and Hb, and also prevent triggering a pro-inflammatory cascade. Hypothesis: We hypothesize CD36 and CD163 knockout would play a role in oxidative stress and inflammation as indicated by neurological function, hemispheric, cortical volumes, and iron staining. Methods: Wildtype and CD36 -/- , CD163 -/- and double CD36 -/- xCD163 -/- mice were injected with 40μL of cerebrospinal fluid (vehicle) or stroma-free Hb. Behavioral rotarod, latency of fall and ambulatory distance tests were utilized to score neurological dysfunction. Brain sections were stained with Cresyl violet and Perls’ Prussian blue. Scanned images were analyzed by an observer blinded to genotypes using algorithm positive pixel counts. Results: At 24h, the CD36 -/- xCD163 -/- mice resulted in an average neurological deficit score of 4.75 (n=9, p<.001), CD36 -/- of 6.34 (n=8, p<.05), CD163 -/- of 6.50 (n=10, p<.05) and WT of 8.23 (n=13). The CD36 -/- ipsilateral and contralateral hemispheric volumes increased respectively 12.4±1.6% (n=11, p=.0005) and 19.4±2.7% that of WT mice (n=6, p=.0001). Double knockouts showed 4.3±1.1% and 6.8±1.9% decreases in ipsilateral and contralateral cortical volumes (n=6, p=.0422, p=.0396). The CD36, CD36 -/- xCD163 -/- and CD163 -/- showed 68.5±13.7% (n=10, p=.003), 41.2±10.3% (n=10, p=.0317), and 30.0±9.8% (n=7, p=.0216) increase in iron staining than WT mice, respectively. Conclusions: Together, the behavioral data, the variations in brain volume, and the significant changes in deposited iron suggest the CD36 and CD163 receptors do play major roles in brain damage and neurological deficits following intracranial bleeding and could be targeted as a potential therapeutic intervention.
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Abu Rmilah, A., G. Lin, and J. Hermann. "P5717Risk of QTC interval prolongation among cancer patients treated with tyrosine kinase inhibitors." European Heart Journal 40, Supplement_1 (October 1, 2019). http://dx.doi.org/10.1093/eurheartj/ehz746.0658.
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Abstract Objective QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice. Methods We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥500 ms, the rate of increase of the QTc interval by ≥60 ms, and the development of complications (VT, TdP, and SCD). Results In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib, and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥500 ms was documented in 53 (18.3%) and QTc progression ≥60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Table 1 demonstrates the findings for each TKI. Findings for TKIs in all patients Total Prolonged QTc QTc ≥500 QTc progression ≥60 VT SCD TdP Imatinib 165 54 13 10 2 Nilotinib 75 33 8 19 Dasatinib 115 58 10 16 2 1 Sunitinib 134 31 1 2 1 1 Pazopanib 165 36 5 6 2 1 Others 248 77 16 18 2 1 1 Conclusion The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib, and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy. Acknowledgement/Funding None
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Medeiros, Daiane Sousa, Marco Antonio Lavorato de Almeida, Rebecca Rhuanny Tolentino Limeira, Candice Regadas Gondim Santiago, Maria Rejane Cruz Araújo, José Klidenberg Oliveira Júnior, and Edeltrudes de Oliveira Lima. "Plantas medicinais utilizadas no tratamento de problemas bucais no estado da Paraíba, Brasil: uma revisão de literatura." ARCHIVES OF HEALTH INVESTIGATION 8, no. 9 (February 20, 2020). http://dx.doi.org/10.21270/archi.v8i9.3252.
Full textAbstract:
Introdução: O uso de plantas medicinais como agente terapêutico é secularmente manifestado e aplicado em diferentes culturas pelo mundo. O estado da Paraíba, localizado na região nordeste do Brasil, apresenta grande parte de sua extensão territorial recoberta pelo clima semiárido, cuja vegetação do tipo caatinga representa uma importante fonte de biomoléculas ativas à saúde. Objetivo: O objetivo desta pesquisa foi realizar um levantamento na literatura sobre dos conhecimentos etnobotânicos da população paraibana no uso de plantas medicinais no tratamento de afecções orais. Material e Método: Realizou-se uma pesquisa nas bases dedados Scielo e Bireme, durante os meses de outubro a novembro de 2017. Encontrou-se 81 artigos, dos quais 17 foram analisados e 10 foram incluídos nesta pesquisa. Resultados: A população relatou o uso de 65 espécies de plantas medicinais na odontologia, pertencentes a 60 gêneros e 34 famílias distinta, com predomínio da família Fabaceae. As espécies mais relatadas pela população foram Punica granatum, Anacardium occidentalee Plectranthus amboinicus. As principais indicações terapêuticas foram antimicrobiana, anti-inflamatória e analgésica. O chá foi o tipo de preparo mais relatado e as folhas e cascas de caule as estruturas vegetais mais utilizadas no preparo. Conclusão: Conclui-se então que o levantamento etnobotânico é de fundamental importância para ampliar o conhecimento científico acerca do uso de plantas medicinais e subsidiar o desenvolvimento de futuros fármacos.Descritores: Etnobotânica; Plantas Medicinais; Fitoterapia; Odontologia.ReferênciasBrasil. Ministério da Saúde. Portaria no 971, de 3 de maio de 2006. Aprova a Política Nacional de Práticas Integrativas e Complementares no Sistema Único de Saúde. Diário Oficial da União, n. 84, seção 1, 2006. 19p.Giraldi M, Hanazaki N. Uso e conhecimento tradicional de plantas medicinais no Sertão do Ribeirão, Florianópolis, Brasil. 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