High BAALC Expression as an Independent Adverse Risk Factor in 309 Patients with Acute Myeloid Leukemia (AML) and Normal Cytogenetics: Results of the SHG’96 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2009-2009
Author(s):  
Claudia D. Baldus ◽  
Christian Thiede ◽  
Clara D. Bloomfield ◽  
Eckhard Thiel ◽  
Gerhard Ehninger

Abstract High mRNA expression levels of the human gene BAALC (Brain And Acute Leukemia, Cytoplasmic) have been shown to be an adverse risk factor in newly diagnosed AML patients (pts; Blood2003;102:1613). The first study included 86 de novo AML pts under the age of 60 with normal cytogenetics and a more favorable FLT3 mutation status, which were uniformly treated on the Cancer And Leukemia Group B protocol 9621. An independent confirmation of these data is necessary, to confirm the impact of BAALC expression in intermediate risk AML pts. Here we present the results of a Süddeutschen Hämoblastosegruppe (SHG) study including 309 adult pts diagnosed with de novo (n=280) and secondary AML (n=29), normal cytogenetics, age <60 years that were uniformly treated on the SHG’96 protocol. Treatment consisted of 2 cycles of induction therapy followed by intensive consolidation including autologous as well as allogeneic stem cell transplantation. Median follow-up for patients alive was 28.7 months (range: 0–86 months). BAALC expression was measured in pretreatment peripheral blood blasts by comparative real-time RT-PCR. Pts having BAALC expression values within the lower 50% were classified as low BAALC and pts having BAALC expression values within the upper 50% were classified as high BAALC. Whereas no correlation was seen between BAALC expression and the prevalence of FLT3 internal tandem duplications (ITD; P=0.16), high BAALC patients had a significantly higher FLT3 mutant/wild-type (wt) ratio as determined by Genescan analysis (mean mutant/wt ratio: 0.59 vs. 0.17; P=0.012). There was no significant difference in the prevalence of MLL partial tandem duplications between the high and the low BAALC group. High BAALC expression was significantly more frequent in FAB groups M0/M1 as compared to the other subtypes (P=0.002). Pts with high BAALC expression levels had a significantly lower CR rate (62.3% vs. 73.5%; P=0.039) and a higher relapse rate (43.8% vs. 28.9%; P=0.030). The overall survival (OS) was significantly shorter for pts with high BAALC expression (OS at 4 years: 29.8% vs. 53.3%; P=0.0018), event-free survival (EFS, at 4 years: 21.6% vs. 45.8%; P=0.0001), and disease-free survival (DFS, at 4 years: 30.4% vs. 57.6%; P=0.0018). Pts with a high FLT3 mutant/wt ratio (greater than 0.8) had a significantly shorter OS and DFS. For patients with a low FLT3 mutant/wt ratio, high BAALC expression allowed identification of pts with a high risk of treatment failure. A multivariate analysis confirmed high BAALC expression and a high mutant/wt FLT3 ratio as the only independent adverse risk factors. For pts with high BAALC expression the hazard ratio of death was 1.7 (95% CI 1.18–2.48; P=0.005), and the hazard ratios for EFS and DFS were 1.8 (95% CI 1.3–2.6; P=0.0003) and 2.0 (95% CI 1.2–3.3; P=0.004), respectively. In conclusion, this independent and larger study strengthens high BAALC expression as one of the most relevant adverse prognostic risk factors in intermediate risk AML pts with normal cytogenetics. Thus, determination of BAALC expression should be considered for risk adaptive treatment strategies.

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1613-1618 ◽  
Author(s):  
Claudia D. Baldus ◽  
Stephan M. Tanner ◽  
Amy S. Ruppert ◽  
Susan P. Whitman ◽  
Kellie J. Archer ◽  
...  

AbstractCytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). Of adults with de novo AML, 45% lack cytogenetic abnormalities, and identification of predictive molecular markers might improve therapy. We studied the prognostic impact of BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel gene involved in leukemia, in 86 de novo AML patients with normal cytogenetics who were uniformly treated on Cancer and Leukemia Group B 9621. BAALC expression was determined by comparative real-time reverse transcriptase–polymerase chain reaction in pretreatment blood samples, and patients were dichotomized at BAALC's median expression into low and high expressers. Low expressers had higher white counts (P = .03) and more frequent French-American-British M5 morphology (P = .007). Compared to low expressers, high BAALC expressers showed significantly inferior overall survival (OS; median, 1.7 vs 5.8 years, P = .02), event-free survival (EFS; median, 0.8 vs 4.9 years, P = .03), and disease-free survival (DFS; median, 1.4 vs 7.3 years, P = .03). Multivariable analysis confirmed high BAALC expression as an independent risk factor. For high BAALC expressers the hazard ratio of an event for OS, EFS, and DFS was respectively 2.7, 2.6, and 2.2. We conclude that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics.


Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 430 ◽  
Author(s):  
Ioanna Mylona ◽  
Maria Dermenoudi ◽  
Nikolaos Ziakas ◽  
Ioannis Tsinopoulos

Background and objectives: The purpose of this study is to determine the impact of the most prominent cardiovascular and metabolic risk factors in patients undergoing cataract surgery. Materials and Methods: The study included 812 consecutive patients undergoing unilateral, uneventful cataract surgery by means of phacoemulsification, at the 2nd Department of Ophthalmology, Medical School, Aristotle University of Thessaloniki, Greece, during a calendar year. Patients were assessed for the type of cataract and the presence of three diseases, under pharmacological treatment, that have been reported as risk factors for the development of cataract (arterial hypertension, diabetes mellitus, and dyslipidemia). Results: There was a statistically significant difference between the types of cataract and individual risk factors (p < 0.001). Hypertension was the most frequentrisk factor, ranging from 43.8% in patients with subcapsular cataracts, 24.3% in patients with nuclear cataracts, 28.6% in patients with cortical cataracts, and 27.6% in patients with mixed type cataracts. There was a statistically significant difference as to the total number of risk factors per cataract type (p < 0.001); almost all patients with subcapsular cataracts had at least one risk factor (98.4%) while this percentage was 90.5% for patients with mixed cataracts, 85.7% for patients with cortical cataracts, and78.6% for patients with nuclear cataracts. Conclusions: Diabetes mellitus did not have a large incidence in our sample as a single risk factor, while hypertension did. This finding raises the importance of early detection of hypertension, a cardiovascular condition that typically progresses undetected for a number of years.


2021 ◽  
Vol 6 (1) ◽  
pp. e003499
Author(s):  
Ryan G Wagner ◽  
Nigel J Crowther ◽  
Lisa K Micklesfield ◽  
Palwende Romauld Boua ◽  
Engelbert A Nonterah ◽  
...  

IntroductionCardiovascular disease (CVD) risk factors are increasing in sub-Saharan Africa. The impact of these risk factors on future CVD outcomes and burden is poorly understood. We examined the magnitude of modifiable risk factors, estimated future CVD risk and compared results between three commonly used 10-year CVD risk factor algorithms and their variants in four African countries.MethodsIn the Africa-Wits-INDEPTH partnership for Genomic studies (the AWI-Gen Study), 10 349 randomly sampled individuals aged 40–60 years from six sites participated in a survey, with blood pressure, blood glucose and lipid levels measured. Using these data, 10-year CVD risk estimates using Framingham, Globorisk and WHO-CVD and their office-based variants were generated. Differences in future CVD risk and results by algorithm are described using kappa and coefficients to examine agreement and correlations, respectively.ResultsThe 10-year CVD risk across all participants in all sites varied from 2.6% (95% CI: 1.6% to 4.1%) using the WHO-CVD lab algorithm to 6.5% (95% CI: 3.7% to 11.4%) using the Framingham office algorithm, with substantial differences in risk between sites. The highest risk was in South African settings (in urban Soweto: 8.9% (IQR: 5.3–15.3)). Agreement between algorithms was low to moderate (kappa from 0.03 to 0.55) and correlations ranged between 0.28 and 0.70. Depending on the algorithm used, those at high risk (defined as risk of 10-year CVD event >20%) who were under treatment for a modifiable risk factor ranged from 19.2% to 33.9%, with substantial variation by both sex and site.ConclusionThe African sites in this study are at different stages of an ongoing epidemiological transition as evidenced by both risk factor levels and estimated 10-year CVD risk. There is low correlation and disparate levels of population risk, predicted by different risk algorithms, within sites. Validating existing risk algorithms or designing context-specific 10-year CVD risk algorithms is essential for accurately defining population risk and targeting national policies and individual CVD treatment on the African continent.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lukasz Markiewicz ◽  
Dariusz Pytel ◽  
Bartosz Mucha ◽  
Katarzyna Szymanek ◽  
Jerzy Szaflik ◽  
...  

The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2GMMP1, -1562 C/TMMP9, -82 A/GMMP12, -511 C/TIL-1β, and 372 T/CTIMP1genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA.In vivopromoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression ofMMP1,MMP9,MMP12, andIL-1βgenes as compared to the control group (P<0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1βcompared to the control group (P<0.001). Allele -1607 1G ofMMP1gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C ofMMP9gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.


2021 ◽  
Vol 11 (5) ◽  
pp. 638
Author(s):  
Ayataka Fujimoto ◽  
Keisuke Hatano ◽  
Toshiki Nozaki ◽  
Keishiro Sato ◽  
Hideo Enoki ◽  
...  

Background: A corpus callosotomy (CC) is a procedure in which the corpus callosum, the largest collection of commissural fibers in the brain, is disconnected to treat epileptic seizures. The occurrence of chemical meningitis has been reported in association with this procedure. We hypothesized that intraventricular pneumocephalus after CC surgery represents a risk factor for postoperative chemical meningitis. The purpose of this study was to analyze the potential risk factors for postoperative chemical meningitis in patients with medically intractable epilepsy who underwent a CC. Methods: Among the patients who underwent an anterior/total CC for medically intractable epilepsy between January 2009 and March 2021, participants were comprised of those who underwent a computed tomography scan on postoperative day 0. We statistically compared the groups with (c-Group) or without chemical meningitis (nc-Group) to determine the risk factors. Results: Of the 80 patients who underwent a CC, 65 patients (25 females and 40 males) met the inclusion criteria. Their age at the time of their CC procedure was 0–57 years. The c-Group (17%) was comprised of seven females and four males (age at the time of their CC procedure, 1–43 years), and the nc-Group (83%) was comprised of 18 females and 36 males (age at the time of their CC procedure, 0–57 years). Mann–Whitney U-tests (p = 0.002) and univariate logistic regression analysis (p = 0.001) showed a significant difference in pneumocephalus between the groups. Conclusion: Postoperative pneumocephalus identified on a computed tomography scan is a risk factor for post-CC chemical meningitis.


2021 ◽  
Vol 104 (Suppl. 1) ◽  
pp. S64-S69

Background: Hypercholesterolemia is a risk factor for developing coronary artery disease. Lifestyle modification including an intake of healthy food as well as medication have approved effect in lowering serum cholesterol. Objective: The primary objective of the present study was to determine the impact of a gamma-oryzanol-enriched rice bran oil, a product of Thailand, on serum cholesterol level. Materials and Methods: A total of in 54 hypercholesterolemic patients were divided into two groups; RBOh (20,000 ppm of gammaoryzanol, n = 27), and RBOn (5,000 ppm gamma-oryzanol, n = 27). The assigned RBO (15 ml) was intake each day for 8 weeks. Fasting serum lipids were measured at baseline and at the 4th and 8th weeks of the intervention. All patients were advised about lifestyle modifications. Results: When compared to the baseline, subjects received RBOh showed a significant difference in 2 parameters including a reduction of cholesterol level at 8th weeks (p-value = 0.0101), and decrease in LDL-C level at the end of 8th weeks (p-value = 0.0013). In the group treated with RBOn, a significant increase in HDL-C level at the end of 8th weeks (p-value = 0.0303) without any effect on total cholesterol or LDL was observed. No sign of toxic effect on liver or renal functions was seen in both treatment groups. Conclusion: RBO with gamma-oryzanol-enriched could decrease cholesterol and LDL-C level in hypercholesterolemic patients. Therefore, gamma-oryzanol-enriched RBO is a functional food that may reduce cardiovascular disease risk factor. Keywords: Hypercholesterolemia, Rice bran oil, Gamma-oryzanol, Oryza sativa


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.


2007 ◽  
Vol 28 (9) ◽  
pp. 1054-1059 ◽  
Author(s):  
G. Ghanem ◽  
R. Hachem ◽  
Y. Jiang ◽  
R. F. Chemaly ◽  
I. Raad

Objective.Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infection. We sought to compare vancomycin-resistant (VR)Enterococcus faecalisbacteremia and VREnterococcus faeciumbacteremia in cancer patients with respect to risk factors, clinical presentation, microbiological characteristics, antimicrobial therapy, and outcomes.Methods.We identified 210 cancer patients with VRE bacteremia who had been treated between January 1996 and December 2004; 16 of these 210 had VRE. faecalisbacteremia and were matched with 32 patients with VRE. faeciumbacteremia and 32 control patients. A retrospective review of medical records was conducted.Results.Logistic regression analysis showed that, compared with VRE. faecalisbacteremia, VRE. faeciumbacteremia was associated with a worse clinical response to therapy (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.07-0.98];P= .046) and a higher overall mortality rate (OR, 8.3 [95% CI, 1.9-35.3];P= .004), but the VRE-related mortality rate did not show a statistically significant difference (OR, 6.8 [95% CI, 0.7-61.8];P= .09). Compared with control patients, patients with VRE. faecalisbacteremia were more likely to have received an aminoglycoside in the 30 days before the onset of bacteremia (OR, 5.8 [95% CI, 1.2-27.6];P= .03), whereas patients with VRE. faeciumbacteremia were more likely to have received a carbapenem in the 30 days before the onset of bacteremia (OR, 11.7 [95% CI, 3.6-38.6];P<.001). In a multivariate model that compared patients with VRE. faeciumbacteremia and control patients, predictors of mortality included acute renal failure on presentation (OR, 15.1 [95% CI, 2.3-99.2];P= .004) and VRE. faeciumbacteremia (OR, 11 [95% CI, 2.7-45.1];P<.001). No difference in outcomes was found between patients with VRE. faecalisbacteremia and control patients.Conclusions.VRE. faeciumbacteremia in cancer patients was associated with a poorer outcome than was VRE. faecalisbacteremia. Recent receipt of carbapenem therapy was an independent risk factor for VRE. faeciumbacteremia, and recent receipt of aminoglycoside therapy was independent risk factor forE. faecalisbacteremia.


Author(s):  
Meryem Keceli Basaran ◽  
Caner Dogan ◽  
Mahmut Bal ◽  
Seda Geylani Gulec ◽  
Nafiye Urganci

Abstract Objective With the increasing prevalence of celiac disease (CD) in the population, possible risk factors are under investigation. Environmental and genetic factors that trigger the immune response have been analyzed for many years. This study investigates the presence of CD in children with rotavirus infection. Rotavirus infection is thought to be a risk factor for CD. Methods Included in the study were 105 of 160 pediatric patients hospitalized due to symptomatic rotavirus infection between 2012 and 2018. These children were screened for CD 45.6 ± 18.2 (14–90) months following the rotavirus infection diagnosed with CD as per ESPGHAN guidelines. Results A total of 105 pediatric patients who had rotavirus gastroenteritis were included in the study. The age of the children with rotavirus infection was 3.98 ± 1 (2–6) months. In terms of CD, it was 45.6 ± 18.2 months. Around 14 to 90 months later, patients were called for control. CD developed in four (3.8%) of the children with rotavirus, whereas none of the children in the control group developed CD. Conclusion Rotavirus infection may be a risk factor for CD through immune mechanisms. There are genetic and various environmental factors for the development of CD. Although the CD's occurrence on children who had rotavirus gastroenteritis in our study also supported this situation, there was no statistically significant difference.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tanya N Turan ◽  
Azhar Nizam ◽  
Michael J Lynn ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  

Purpose: SAMMPRIS is the first stroke prevention trial to include protocol-driven aggressive management of multiple vascular risk factors. We sought to determine the impact of this protocol on early risk factor control in the trial. Materials and Methods: SAMMPRIS randomized 451 patients with symptomatic 70%-99% intracranial stenosis to aggressive medical management or stenting plus aggressive medical management at 50 USA sites. For the primary risk factor targets (SBP < 140 mm/Hg (<130 if diabetic) and LDL < 70 mg/dL), the study neurologists follow medication titration algorithms and risk factor medications are provided to the patients. Secondary risk factors (diabetes, non-HDL, weight, exercise, and smoking cessation) are managed with assistance from the patient’s primary care physician and a lifestyle modification program (provided). Sites receive patient-specific recommendations and feedback to improve performance. Follow-up continues, but the 30-day data are final. We compared baseline to 30-day risk factor measures using paired t-tests for means and McNemar tests for percentages. Results: The differences in risk factor measures between baseline and 30 days are shown in Table 1. Conclusions: The SAMMPRIS protocol resulted in major improvements in controlling most risk factors within 30 days of enrollment, which may have contributed to the lower than expected 30 day stroke rate in the medical group (5.8%). However, the durability of this approach over time will be determined by additional follow-up.


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