The Majority of Myeloma Patients Are Hypogonadal but This Is Not Associated with High Risk Cytogenetics

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5329-5329
Author(s):  
Beau Snoad ◽  
Samantha Hudzik ◽  
Douglas W Sborov ◽  
Nita Williams ◽  
Desiree Jones ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Serum Testosterone ◽  
Clinic Visit ◽  
Total Testosterone ◽  
Testosterone Levels ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Introduction: Hypogonadism, i.e. low total testosterone, is present in approximately a quarter of men older than 70 years (Harman SM et al, J. Clin Endo & Met, 2001, PMID 11158037 and Wu FCW et al, J Clin Endo & M et, 2008, PMID 18270261). Myeloma patients are known to suffer from fatigue and decreased functional performance, mood disturbances, and anemia; similar trends have been found in people with hypogonadism. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558). We hypothesized that total testosterone levels will be associated with overall survival from the time of diagnosis, presence of 1q21 amplification by CD138-selected FISH, anemia, and anti-depressant use. Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total testosterone was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Less than 325 ng/dL was defined as the hypogonadal range, and testosterone was divided into <100 (group 1), 100-240 (group 2), 240-325 (group 3), and greater than 325 ng/dL (group 4), although normal testosterone decreases with age. Female patient testosterone levels were also analyzed and divided into <10 (group 1), 10-60 ng/dL (group 2), and >60 ng/dL (group 3). A retrospective chart review was initiated to review all myeloma patients with a serum testosterone drawn at the time of their initial clinic visit to OSU. Results: Among 418 male MM patients, median age was 65 y.o. (range 24-95), 86% were Caucasian and 14% African-American, and the distribution of ISS stage was 32% stage 1, 22% stage 2, and 19% stage 3 with 28% missing staging data. Cytogenetic data was missing from 28% of patients. Out of 418 male MM patients, 29 (7%) had serum testosterone <100, 202 (48%) with testosterone 100-240, 79 (19%) with testosterone 241-325, and 108 (26%) > 325 ng/dL. Out of 172 female MM patients, 44 (26%) had an undetectable serum testosterone, 120 (70%) with testosterone 10-60, and 8 (5%) with testosterone > 60. Among male MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum testosterone including all 4 groups demonstrated no significant differences (p=0.917) with only 80 events. Among 275 male MM patients with cytogenetic information available, there was no correlation between presence of 1q21 trisomies or tetrasomies and overall survival (r=0.0714, p=0.238). There was a strong and expected correlation between testosterone and BMI (r=0.14, p=0.00468). Among 161 total female MM patients, log-rank analysis with serum testosterone including all 3 groups also demonstrated no differences (p=0.416) with only 29 events in total. Among 101 females with cytogenetic information, there was also no correlation with 1q21 amplification (r=0.0895, p=0.373). Conclusion: The majority of male MM patients (74%) have secondary hypogonadism and approximately half have total testosterone levels <240 ng/dL. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with anemia and medication use (specifically opiates and anti-depressants) will also be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels

2004 ◽  
Vol 89 (3) ◽  
pp. 1174-1180 ◽  
Author(s):  
Benjamin Z. Leder ◽  
Jacqueline L. Rohrer ◽  
Stephen D. Rubin ◽  
Jose Gallo ◽  
Christopher Longcope
Keyword(s):  
Short Form ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Total Testosterone ◽  
Elderly Men ◽  
Symptom Index ◽  
Testosterone Levels ◽  
Group 2 ◽  
American Urological Association ◽  
Group 1

Abstract As men age, serum testosterone levels decrease, a factor that may contribute to some aspects of age-related physiological deterioration. Although androgen replacement has been shown to have beneficial effects in frankly hypogonadal men, its use in elderly men with borderline hypogonadism is controversial. Furthermore, current testosterone replacement methods have important limitations. We investigated the ability of the orally administered aromatase inhibitor, anastrozole, to increase endogenous testosterone production in 37 elderly men (aged 62–74 yr) with screening serum testosterone levels less than 350 ng/dl. Subjects were randomized in a double-blind fashion to the following 12-wk oral regimens: group 1: anastrozole 1 mg daily (n = 12); group 2: anastrozole 1 mg twice weekly (n = 11); and group 3: placebo daily (n = 14). Hormone levels, quality of life (MOS Short-Form Health Survey), sexual function (International Index of Erectile Function), benign prostate hyperplasia severity (American Urological Association Symptom Index Score), prostate-specific antigen, and measures of safety were compared among groups. Mean ± sd bioavailable testosterone increased from 99 ± 31 to 207 ± 65 ng/dl in group 1 and from 115 ± 37 to 178 ± 55 ng/dl in group 2 (P &lt; 0.001 vs. placebo for both groups and P = 0.054 group 1 vs. group 2). Total testosterone levels increased from 343 ± 61 to 572 ± 139 ng/dl in group 1 and from 397 ± 106 to 520 ± 91 ng/dl in group 2 (P &lt; 0.001 vs. placebo for both groups and P = 0.012 group 1 vs. group 2). Serum estradiol levels decreased from 26 ± 8 to 17 ± 6 pg/ml in group 1 and from 27 ± 8 to 17 ± 5 pg/ml in group 2 (P &lt; 0.001 vs. placebo for both groups and P = NS group 1 vs. group 2). Serum LH levels increased from 5.1 ± 4.8 to 7.9 ± 6.5 U/liter and from 4.1 ± 1.6 to 7.2 ± 2.8 U/liter in groups 1 and 2, respectively (P = 0.007 group 1 vs. placebo, P = 0.003 group 2 vs. placebo, and P = NS group 1 vs. group 2). Scores for hematocrit, MOS Short-Form Health Survey, International Index of Erectile Function, and American Urological Association Symptom Index Score did not change. Serum prostate-specific antigen levels increased in group 2 only (1.7 ± 1.0 to 2.2 ± 1.5 ng/ml, P = 0.031, compared with placebo). These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Serum estradiol levels decrease modestly but remain within the normal male range. The physiological consequences of these changes remain to be determined.

Abstract P711: Factors Affecting Intracranial Aneurysm Incidence and Phenotypes at Risk of Rupture in Autosomal Dominant Polycystic Kidney Disease

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Chan-Hyuk Lee ◽  
Hyunjin Ryu ◽  
Curie Ahn ◽  
Hyun-Seung Kang ◽  
Seul-Ki Jeong ◽  
...  
Keyword(s):  
High Risk ◽  
Intracranial Aneurysm ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Mitral Inflow ◽  
Group 3 ◽  
Autosomal Dominant Polycystic Kidney ◽  
Group 2 ◽  
Group 1 ◽  
Deceleration Time

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominant genetic disorder in which cysts of various sizes invade the renal parenchyma. Intracranial aneurysms occur in 8-12% of ADPKD patients, which is approximately 3-4 times the rate of the healthy population. However, research on factors related to aneurysm incidence and rupture in patients with ADPKD is insufficient. Objective: We analyzed the factors associated with risk of aneurysm incidence and phenotype in ADPKD patients. Methods: From the ADPKD registry in the tertiary hospital, we screened patients with cerebral angiography enrolled between January 2007 and May 2017. Then, 926 enrolled patients were classified into three groups according to the intracranial aneurysm incidence and phenotype (multiplicity, size, location): no intracranial aneurysm (Group 1); low-risk intracranial aneurysm (Group 2); high-risk intracranial aneurysm (Group 3). We analyzed the difference of patients’ demographic factors, cardiovascular risk factors, laboratory data, echocardiographic data, and imaging data between groups. Results: The prevalence [C1] of intracranial aneurysm in ADPKD patients was 16.0%. Aneury[C2] sm-positive group (Group 2 and 3, n=148) was significantly older (p<0.001) and had a greater proportion of females (p<0.001) than patients in the aneurysm-negative group (Group 1, n=778). Compared to Group 1, Group 3 was significantly associated with age (odds ratio (OR) 1.027, p=0.007), female sex (OR 3.184, p<0.001), dyslipidemia (OR 0.460, P=0.001), basilar artery dolichoectasia (OR 8.443, p=0.016), and mitral inflow deceleration time (OR 1.005, p=0.039). Conclusion: Factors associated with a high-risk aneurysms were age, sex, dolichoectasia, dyslipidemia, and mitral inflow deceleration time in ADPKD patients. Identification of these factors would help detect high risk aneurysms and manage the aneurysms in ADPKD patients.

scholarly journals Appropriate secondary prevention and clinical outcomes after acute myocardial infarction according to atherothrombotic risk stratification: The FAST-MI 2010 registry

2018 ◽  
Vol 26 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Victoria Tea ◽  
Marc Bonaca ◽  
Chekrallah Chamandi ◽  
Marie-Christine Iliou ◽  
Thibaut Lhermusier ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Secondary Prevention ◽  
High Risk Patients ◽  
Risk Patients ◽  
St Elevation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background Full secondary prevention medication regimen is often under-prescribed after acute myocardial infarction. Design The purpose of this study was to analyse the relationship between prescription of appropriate secondary prevention treatment at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. Methods We used data from the 2010 French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) registry, including 4169 consecutive acute myocardial infarction patients admitted to cardiac intensive care units in France. Level of risk was stratified in three groups using the TRS-2P score: group 1 (low-risk; TRS-2P=0/1); group 2 (intermediate-risk; TRS-2P=2); and group 3 (high-risk; TRS-2P≥3). Appropriate secondary prevention treatment was defined according to the latest guidelines (dual antiplatelet therapy and moderate/high dose statins for all; new-P2Y12 inhibitors, angiotensin-converting-enzyme inhibitor/angiotensin-receptor-blockers and beta-blockers as indicated). Results Prevalence of groups 1, 2 and 3 was 46%, 25% and 29% respectively. Appropriate secondary prevention treatment at discharge was used in 39.5%, 37% and 28% of each group, respectively. After multivariate adjustment, evidence-based treatments at discharge were associated with lower rates of major adverse cardiovascular events (death, re-myocardial infarction or stroke) at five years especially in high-risk patients: hazard ratio = 0.82 (95% confidence interval: 0.59–1.12, p = 0.21) in group 1, 0.74 (0.54–1.01; p = 0.06) in group 2, and 0.64 (0.52–0.79, p < 0.001) in group 3. Conclusions Use of appropriate secondary prevention treatment at discharge was inversely correlated with patient risk. The increased hazard related to lack of prescription of recommended medications was much larger in high-risk patients. Specific efforts should be directed at better prescription of recommended treatment, particularly in high-risk patients.

scholarly journals Quality of Oral Anticoagulation with Vitamin K Antagonists in 'Real-World' Patients: Lessons from a Six Years Audit Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1159-1159
Author(s):  
Fernanda Leite ◽  
Ângela Leite ◽  
Sara Ferreira ◽  
Jorge Coutinho
Keyword(s):  
Vitamin K ◽  
Therapeutic Range ◽  
Patient Population ◽  
Conflicts Of Interest ◽  
Vitamin K Antagonists ◽  
Recall Interval ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Introduction: Among patients receiving vitamin K antagonists (VKA) therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. This requires regular monitoring and appropriate dose adjustment. It has been reported that anticoagulation clinics should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. Previously (in a study between September 2006 and June 2012), we have reported that patients with longer INR recall interval (4-8 weeks) showed no decrease of monitoring quality and that it would be safe to increase time between measurements. Aim: Since actual recommendations for improving TTR include shortening INR recall interval (Lip et al. 2018) we aimed to evaluate the quality of anticoagulation monitoring after having increased time between measurements beyond the 4-8 weeks recall interval. Methodology: We retrospectively analyzed 37931 appointments of 6 consecutive years (July 2012 to July 2018) corresponding to 1587 patients that are regularly followed up at an outpatient Anticoagulation Clinic of a central hospital under anticoagulation for at least 8 weeks, using TTR determined by Rosendaal method. Patients were divided according to target INR in three groups: Group 1 with target INR 2-3, including 1430 patients corresponding to 30743 appointments with mean age 69±15 years (mean±SD), majority (46.4%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 125 patients corresponding to 5439 appointments with mean age 67±12 years, majority (85.6%) with mechanical heart valves; Group 3 with target INR 3-4, including 32 patients corresponding to 1749 appointments with mean age 62±14 years, majority (62.5%) with antiphospholipid syndrome. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests and correlations were performed. Results: The 1587 patient population, 50.5% male, mean age of 68±17 years and 90.1% in Group 1, showed a mortality of 18%. A point-biserial correlation was run to determine the relationship between mortality and gender, age, INR group and diagnostic. Mortality was correlated with diagnosis (57.2% with AF) (rpb = -.071, n = 1587, p = .004), male gender (60%) (rpb = -.089, n = 1587, p <.001) and age (75±12) (rpb = .175, n= 1587, p<.001) but not with INR group (rpb = -.017, n = 1587, p = .499). Indeed, between groups mortality was not different [Χ2(2)=.492; p=.782; φ=.018] nor mean age [F(2, 1584)=2.588; p=.078; η2=.003], but gender distribution was unequal [Χ2(2)= 10.815; p=.004; φ=.083] with male predominating in Group 1 (51.9%) and female in Group 2 (60.8%) and 3 (65.6%). Patients in Group 1, corresponding to 90.1% of the total population, had TTR of 72%, patients in Group 2 had TTR of 69% and patients in Group 3 had TTR of 60%. Comparatively to the previous study (2006-2012), we noticed a significant decrease in patient population / appointments size (2087/ 61988) (p <.001) with a decrease of TTR in Group 1 (1927 patients) (83%) and Group 2 (120 patients) (74%) but a TTR increase in Group 3 (40 patients) (54%) (p <.001). Conclusions and Discussion: More than 90% of the population under VKA treatment showed effective TTR which may infer safety in increasing INR recall interval. The TTR decrease with a smaller population may be explained by the introduction of direct oral anticoagulants in patients with less comorbidities. The increase of TTR in patients with higher INR target suggests a better management of patients under VKA therapy that is actually the only choice for challenging patients. Disclosures No relevant conflicts of interest to declare.

Survival of Patients with High-Risk Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

2021 ◽  
Vol 104 (6) ◽  
pp. 895-901
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
High Risk ◽  
Congenital Heart ◽  
First Year ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD) with uncorrected left-to-right shunts. Currently, no consensus guideline exists on the management of PAH-CHD in children, especially those who do not meet operability criteria. Objective: To compare survival between three groups of high-risk PAH-CHD, group 1: total correction including both surgical and percutaneous intervention, group 2: palliative treatment, and group 3: conservative with medical treatment group. Materials and Methods: All pediatric patients with PAH-CHD that underwent cardiac catheterization between January 1, 2008 and December 31, 2017 were retrospectively reviewed. Inclusion criteria were high risk PAH-CHD patients who had pulmonary vascular resistance (PVR) greater than 6 Wood unit·m² and PVR-to-SVR ratio greater than 0.3 evaluated in room air. Exclusion criteria were younger than three months of age, severe left side heart disease with pulmonary capillary wedge pressure greater than 15 mmHg, obstructive total pulmonary venous return, and single ventricle physiology. The Kaplan-Meier analysis was performed from the date of PAH diagnosis to the date of all-cause mortality or to censored date at last follow-up. Results: Seventy-six patients with a median age at diagnosis of 27.5 months (IQR 14.5 to 69.0 months) were included in this study. The patients were divided into three subgroups and included 38 patients (50.0%) in group 1, six patients (7.9%) in group 2, and 32 patients (42.1%) in group 3. The median follow-up time was 554 days (IQR 103 to 2,133 days). The overall mortality was 21.7%. One-year survival in patients with simple lesion in group 1 and 3 were 79.5% and 87.5% and patients with complex lesions in group 1, 2, and 3 were 93.8%, 83.3%, and 73.1%, respectively. The results showed that most mortalities occurred in the first year. There were no statistically significant differences in survival among difference types of treatment (log rank test, p=0.522). Conclusion: The mortality of high-risk PAH-CHD patients were not different among those who underwent corrective surgery, palliative, or conservative treatment. The mortality was high in the first year after PAH diagnosis and remain stable afterward. Management decision for an individual with high-risk PAH-CHD patients requires comprehensive clinical assessment to balance the risks and benefits before making individualized clinical judgment. Keywords: Pulmonary hypertension; Congenital heart disease; High-risk patients

Clinical Outcomes According to Genomic Abnormalities in 566 Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib-Based Regimens.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1868-1868 ◽  
Author(s):  
Michele Cavo ◽  
Sara Bringhen ◽  
Nicoletta Testoni ◽  
Paola Omedè ◽  
Giulia Marzocchi ◽  
...  
Keyword(s):  
High Risk ◽  
First Line ◽  
Cytogenetic Abnormalities ◽  
Post Hoc Analysis ◽  
Significant Difference ◽  
Genomic Aberrations ◽  
Group 3 ◽  
Group 2 ◽  
Post Hoc ◽  
Group 1

Abstract Abstract 1868 Poster Board I-893 Introduction Bortezomib was initially reported to overcome the poor prognosis related to the presence of del(13q) in patients with advanced refractory/relapsed multiple myeloma (MM). However, more recent evaluations of genomic aberrations in MM provided demonstration that only t(4;14) and del(17p) retained prognostic value for both EFS and OS, thus identifying a subgroup of patients at high risk of progression or death. The combination of bortezomib with melphalan and prednisone, actually licensed as first-line therapy for MM patients who are not eligible for autologous stem-cell transplantation (ASCT), showed comparable activities in terms of time to progression and OS among patients with or without high-risk cytogenetic profiles. However, the number of high-risk patients analyzed was very limited, due to the low frequency of these genomic abnormalities. To more carefully assess the role of bortezomib in patients with high-risk cytogenetics [(e.g. carrying t(4;14) and/or del(17p)], we performed a post-hoc analysis of two phase 3 studies of first-line bortezomib-based regimens for the treatment of a large series of MM patients. Both studies are actually conducted by the Italian Myeloma Network GIMEMA. Patients and methods The activity of three different bortezomib-based regimens in terms of achievement of best high-quality response (immunofixation negative CR) and PFS was analyzed. Regimens evaluated were bortezomib-thalidomide-dexamethasone (VTD), bortezomib-melphalan-prednisone (VMP) and bortezomib-melphalan-prednisone-thalidomide (VMPT). VTD was followed by ASCT. Treatment details are as follows: VTD (Bortezomib, 1.3 mg/m2 twice-weekly, every 21/d cycle; Thalidomide, 200 mg/d; Dexamethasone, 320 mg/cycle); VMP (Bortezomib 1.3 mg/m2 on d 1, 8, 15 and 22, every 35/d cycle; Melphalan, 9 mg/m2 on d 1 through 4, every cycle; Prednisone, 60 mg/m2 on d 1–4 of each cycle); VMPT (VMP, as previously described; Thalidomide, 50 mg/d). A total of 566 patients for whom results of interphase FISH analysis at diagnosis were available for the presence or absence of del(13q) and/or t(4;14) and/or del(17p), were included in the present study. Three cytogenetic subgroups of patients were identified, including those without genomic abnormalities (group 1; n=257), those with del(13q) alone (group 2; n=162) and those who carried t(4;14) and/or del(17p) with or without del(13q) (group 3; n=147). For the purpose of the present analysis, clinical outcomes (e.g. CR rate and PFS) of patients treated with the 3 bortezomib-based regimens were compared according to the presence or absence of different genomic aberrations (e.g. group 1 vs 3 and group 2 vs 3). Results Overall, the frequency of patients belonging to group 1 (no abnormalities), group 2 [del(13q) alone] and group 3 [t(4;14)±del(17p)] was 45%, 29% and 26%, respectively. Comparable rates of genomic aberrations were detected in patients treated with the 3 bortezomib-based regimens [no genetic abnormalities: 46% in VTD vs 48% in VMP vs 42% in VMPT; del(13q) alone: 30% in VTD vs 28% in VMP vs 28% in VMPT; t(4;14)±del(17p): 24% in VTD vs 24% in VMP vs 30% in VMPT]. No statistically significant difference in terms of CR rate was detected by comparing patients in group 3 with those in group 1 (38% vs 31.5%, respectively; P=0.1) and in group 2 (48%, P=0.07). The 2-year projected PFS was 63% for patients with high-risk cytogenetics vs 71% for those with del(13q) alone (P=0.1) vs 75% for patients without cytogenetic abnormalities (P=0.01). The finding that in the high-risk cytogenetic subgroup the VMP regimen comprising once-weekly standard-dose bortezomib effected the lowest rate of CR and PFS may explain, at least in part, the longer PFS for the subgroup without cytogenetic abnormalities. Indeed, after exclusion from the analysis of the VMP regimen, no statistically significant difference in terms of PFS was seen among VTD- and VMPT-treated patients according to the presence of high-risk cytogenetics or the absence of genomic abnormalities (P=0.09). Conclusions These results, based on a post-hoc analysis of patients with different age and treatment exposure, should be cautiously interpreted, although consistencies exist between them and previous reports on the activity of bortezomib in MM with high-risk cytogenetic abnormalities. Further analyses of large series of homogeneously treated patients are needed before firm conclusions can be drawn about the ability of bortezomib-based regimens to overcome the adverse prognosis related to t(4;14) and/or del(17p). Disclosures: Cavo: Ortho Biotech, Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Millennium Pharmaceuticals: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Boccadoro:Ortho Biotech, Janssen-Cilag: Honoraria, Speakers Bureau. Palumbo:Ortho Biotech, Janssen-Cilag: Honoraria; Celgene: Honoraria, Speakers Bureau.

The Combination of the EBMT Score and the HCT-CI Is Not Better Than the HCT-CI Alone in the Prediction of NRM and OS in Patients Undergoing Allogeneic Hematopoietic Transplantation with Reduced-Toxicity Conditioning

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1925-1925
Author(s):  
Pere Barba ◽  
David Valcarcel ◽  
Lucía López-Corral ◽  
Francesc fernandez-Aviles ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Lymphocytic Leukemia ◽  
Score Distribution ◽  
Predictive Capacity ◽  
Group 3 ◽  
Group 2 ◽  
Reduced Toxicity ◽  
The Impact ◽  
Group 1

Abstract Abstract 1925 In recent years, several pre-transplant models have been developed to predict the outcome after hematopoietic cell transplantation (HCT) through the selection of the best candidates and conditioning regimens. Two models are the most popular one each side of the Atlantic: the HCT Comorbidity Index (HCT-CI) and the European Blood and Marrow Transplantation (EBMT) score. Their predictive capacity has been demonstrated in several studies. Since these models are focused on different pre-HCT characteristics (HCT-CI on comorbidities and the EBMT score on more classical risk factors) we hypothesized that the combination of the two could improve their individual predictive capacity. To that end, we retrospectively analyzed pre-HCT characteristics of all consecutive patients receiving a reduced-toxicity allogeneic HCT (allo-HCT) in 4 Spanish centers from 1999–2008. The HCT-CI and the EBMT scores were calculated as originally defined. Patients were then classified according to the HCT-CI in the original categoriesas originally defined and regardingto the EBMT score in two groups according to the median score of the whole cohort. Multivariate analyseis including pre-HCT characteristics were performed using Cox proportional Hazard models and taking into account the competitive risk structure. The predictive capacity of each model was calculated using the c-statistics. Patients were included in the same protocol of reduced-toxicity allo-HCT with fludarabine-based conditioning in combination with melphalan (70–140 mg/m2) or busulfan (8–10 mg/kg). The median follow-up for survivors was 51 months (range 3–123). A total of 442 recipients (80% transplanted from HLA identical siblings) were included. Most frequent diseases were acute leukemia/MDS (n=156, 35%) and non-Hodgkin lymphoma/chronic lymphocytic leukemia (n=125, 28%). The HCT-CI score distribution was: score 0 (n=87, 20%), score 1–2 (n=130, 29%) and score ≥3 (n=225, 51%) while for the EBMT score was 0–2 (n=62, 14%), 3–4 (n=194, 44%) and >4 (n=187, 42%). The probability of 100-day Non-Relapse Mortality (NRM), 4y-NRM and 4y-overall survival (OS) for the whole cohort were 12% (95%CI 11–14), 35% (95%CI 33–38) and 45% (95%CI 48–50), respectively. In the multivariate analysis, the HCT-CI had and impact on 4y-NRM (score 0: HR 1.0; scores 1–2: HR 1.6 [95%CI 0.9–3], p=0.09; scores ≥ 3: HR 2.3 [95%CI 1.3–3.8], p=0.003) and 4y-OS (score 0:HR of death 1.0; scores 1–2: HR 1.3 [95%CI 0.8–2], p=0.2; scores >2: HR 1.9 [95%CI 1.3–2.8], p=0.002) while the EBMT score did not (p=0.4 and p=0.5, respectively). Using the two models we classified the patients were classified into 3 groups: patients with low HCT-CI (0–2) and low EBMT score (<4) (Group 1), patients with high HCT-CI or high EBMT score (Group 2) and patients with both high HCT-CI and EBMT score (Group 3). The HR for 4y-NRM were: group 1 (HR 1.0), group 2 (HR 1.1 [95%CI 0.6–2], p=0.7), group 3 (HR 1.8 [95%CI 1–3], p=0.04) and for 4y-OS was: group 1 (HR 1.0), group 2 (HR 1 [95%CI 0.6–1.5], p=0.8), group 3 (HR 1.6 [95%CI 1–2.3], p=0.04). Regarding the predictive capacity of each model, the HCT-CI alone captured 58% (c- 95%CI: 53–62), the EBMT score 54% (c- 95%CI: 51–58) while the combination of the two models captured 57% (c- 95%CI: 53–61) of the patients. Finally, the impact of EBMT score was explored in each HCT-CI group. In patients with HCT-CI scores of 0 and 1–2, the EBMT score did not have an impact on NRM and OS. In the cohort of high HCT-CI score (>2), patients with low EBMT score showed a trend to lower risk of NRM (HR 0.6 [95%CI 0.3–1], p=0.08) with a similar risk as for patients with HCT-CI of 1–2 (Figure 1). In conclusion, high HCT-CI scores but not high EBMT scores are associated with worse outcome in patients undergoing reduced toxicity allo-HCT. The addition of the EBMT score contributes little to the HCT-CI, except maybe for patients with more and severe comorbidities. Figure 1. Probability of NRM according to the HCT-CI for all patients and according to the EBMT score in the 225 patients with HCT-CI >2 (MVA) Figure 1. Probability of NRM according to the HCT-CI for all patients and according to the EBMT score in the 225 patients with HCT-CI >2 (MVA) Disclosures: No relevant conflicts of interest to declare.

Bleeding Intensity Following Tooth Extraction Is Moderated by Anxiety Independently of Treatment with anticoagulants– Development of an Internet Based Questionnaire Across Countries

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4364-4364
Author(s):  
Shabnam Zolfaghari ◽  
Svetlana Marx ◽  
Jeelka Fischer ◽  
Parastoo Hassani ◽  
Marinella Damian ◽  
...  
Keyword(s):  
Personality Traits ◽  
Tooth Extraction ◽  
Conflicts Of Interest ◽  
Physiological Stress ◽  
Personality Inventory ◽  
The Self ◽  
Bleeding Complications ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Abstract 4364 Anticoagulation with dose adjusted vitamin-K antagonists (VKA, therapeutic range of the international normalized ratio (INR) of 2 to 3) and low dose aspirin (65 to 330 mg daily) enhance bleeding following tooth extraction. However, intensity of bleeding varies substantially between patients. Guidelines disagree regarding interruption or continuation of anticoagulation for tooth extraction. We hypothesized that personality traits may moderate bleeding intensity under anticoagulation. A total of 180 patients (77 female, 103 male, 49.9+15.3 years (mean, standard deviation)) underwent tooth extraction without interruption of anticoagulation. Sixty three patients did not take any anticoagulant (group 1), 60 patients were on aspirin (group 2), and 57 patients on VKA (INR 2–3, group 3). Patients completed a validated state-trait anxiety inventory (STAI), a personality inventory with 12 dimensions (Freiburg personality inventory (FPI)), and a self-developed questionnaire on general attitudes regarding general feeling and anxiety before tooth extraction. Dentists (JF, PH) rated bleeding intensity ranging from 0 to 9 according a standardized protocol. Intensity of bleeding after tooth extraction was higher in group 3 (score <5 in 40%, score >5 in 60% of patients) compared to groups 1 (40% and 60%) and 2 (53% and 47%) and higher in group 2 compared to group 1 (p<0.005, chi-square test) as expected. Higher anxiety values in STAI questionnaire correlated positively with higher bleeding scores (p<0.0001). High values of some of the FPI dimensions correlated positively with self-consciousness (p<0.0001), physical complaints (p<0.001), and emotionality (p<0.0001) life, and negatively with satisfaction (p<0.02) and extraversion (p<0.003) without differences between groups 1 to 3. Anxiety symptoms of the self questionnaire were identified as moderating factor on bleeding intensity following tooth extraction independently of anticoagulation (p<0.0001) according multinominal regression analysis. Other items of the self questionnaire such as physiological stress symptoms, regular performance of visits, bad experience with dentists, and pains during tooth extraction did not influence bleeding intensity. A short questionnaire is developed to identify the anxiety score of patients as a tool for a non pharmaceutical medical intervention to reduce bleeding complications following tooth extraction. Because differences of the moderating effect of bleeding by personality traits may exist between cultures, the questionnaire will be made available across countries www.blutverduennung.uni-hd.de Disclosures: No relevant conflicts of interest to declare.

Therapy Related Acute Lymphoblastic Leukemia: Pethema Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4994-4994
Author(s):  
Nicholas John Kelleher ◽  
David Gallardo ◽  
Salut Brunet ◽  
Pau Montesinos ◽  
Josep-Maria Ribera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Cytotoxic Therapy ◽  
Survival Group ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Therapy related acute lymphoblastic leukemia, a subset of secondary acute lymphoblastic leukemia has been estimated as accounting for between 1.2 and 6.9% of all adult acute lymphoblastic leukemia cases. It has been associated with an increased frequency of high risk cytogenetic alterations and with worse clinical outcomes. It has been suggested these patients should be included in high risk treatment protocols. Method In order to evaluate these characteristics in a group of similar patients we contacted centres working within the PETHEMA group to request data on patients diagnosed with ALL asking for clinical information including the presence or absence of previous neoplasia and of previous cytotoxic therapy along with treatment responses and survival data. Results We received information on 429 patients of whom 22 had received cytotoxic therapy for a prior neoplasm.Patients were divided into group 1 with prior cytotoxic therapy, group 2 with prior neoplasia without cytotoxic therapy and group 3 de novo ALL. We found patients in group 3 to be younger than the other two groups Group 1( 55 years) Group 2 (65 years) Group 3 (34 years) (p=0.001). No statistically significant difference was shown for white cell count, cytopenias, CNS involvement, LDH or for B versus T immunophenotype. Nor did our series show a significant difference in the frequencies of high risk cytogenetics between the groups. Figures for complete remission [Group 1- 13 (93%); Group 2- 6 (75%); Group 3-346 (85%) p=0.477] were higher in group 1 therapy related ALL compared with de novo patients without reaching clinical significance. Nor was a statistically significant difference shown for 3 year overall survival [Group 1 (80%); Group 2 (38%); Group 3 (47%) p=0.151] , 3 year event free survival [Group 1 (67%); Group 2 (38%); Group 3 (42%) p=0.24] or for complete remission duration [Group 1 (75%);Group 2 (50%); Group 3 (60%) p=0.462] Conclusion Apart from age, our series did not show an increase in poor risk clinical or cytogenetic features in therapy related ALL patients compared with de novo disease cases and nor was clinical outcome demonstrated to be worse. This would suggest that risk stratification should be carried out using currently recognized parameters without specifically taking into account the status of therapy related disease. Disclosures: No relevant conflicts of interest to declare.

Impact of Varicocele and Varicocele Surgery on Semen Quality, Erectile Function and Serum Hormone Levels

2018 ◽  
Vol 1 (1) ◽  
pp. 129-136
Author(s):  
Badereddin Mohamad Al-Ali ◽  
Emma Persad ◽  
Andreas Lunacek ◽  
Christof Mrstik ◽  
Eugen Plas
Keyword(s):  
Testosterone Level ◽  
Erectile Function ◽  
Semen Quality ◽  
Semen Analysis ◽  
Serum Testosterone ◽  
T Test ◽  
Serum Testosterone Level ◽  
Testosterone Levels ◽  
Group 2 ◽  
Group 1

Introduction: Many studies suggest that varicoceles are associated with hypogonadism and varicocele repair can increase testosterone levels and improve erectile function.Aim: The aim of this retrospective study was to analyze the impact of varicocele and varicocele surgery on testosterone level, semen quality, and erectile function.Methods: Our study included 265 infertile males with a clinical varicocele. This group was divided into three groups: group 1 (193) patients who did not receive surgery, group 2 (72 patients) who were operated on according to the Palomo procedure and group 3 (28 patients), who acted as a control group without a varicocele. All patients completed the International Index of Erectile Function IIEF-5 (German version) and underwent semen analysis. Serum testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured at inclusion into the study and after surgery.Main outcome measures: Changes in semen quality, erectile function, and serum hormones after surgery.Results: The IIEF-5 scores in groups 1 and 2 were 21.01 ± 2.2; and 21.74 ± 1 respectively, and the resulting t-test for equality of variance was significant (p < 0.0001). Total testosterone level in groups 1 and 2 were 3.16 ± 0.37 and 3 ± 0.01, respectively, and the resulting t-test for equality of variance was significant (p < 0.0001). The results of the semen analysis were better in group 2 (after surgery) (28.6%, p < 0.001) in comparison to group 1. Interestingly, pre-operative serum testosterone levels were lower in patients with later improvement of semen analysis (p = 0.05). Body mass index (p = 0.8), pre-operative serum FSH (p = 0.9), LH (p = 0.2), and nicotine consumption (p = 0.6) were similar in both the group that saw improvement and the group with no change in semen quality.Conclusion: Semen quality improved in 28.6% of patients after varicocele surgery. Erectile dysfunction (ED) improved after varicocele surgery. We report that lower pre-operative serum testosterone level might be a possible indicator for successful surgical outcome.

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