scholarly journals Hypertension and Its Associations with Dental Status: Data from the Dental, Oral, Medical Epidemiological (DOME) Nationwide Records-Based Study

2021 ◽  
Vol 10 (2) ◽  
pp. 176
Author(s):  
Galit Almoznino ◽  
Avraham Zini ◽  
Ron Kedem ◽  
Noam E. Protter ◽  
Dorit Zur ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Multivariate Analysis ◽  
Fatty Liver ◽  
Western Europe ◽  
Univariate Analysis ◽  
Positive Association ◽  
Dental Status ◽  
Older Age ◽  
Birth Country ◽  
Male Sex

Conflicting results have been published regarding the associations between dental status and hypertension. This study aims to explore whether or not hypertension is associated with dental status among young to middle-aged adults. To that end, data from the Dental, Oral, Medical Epidemiological (DOME) study were analyzed. The DOME is a cross-sectional records-based study that combines comprehensive socio-demographic, medical, and dental databases of a nationally representative sample of military personnel. Included were 132,529 subjects aged 18–50 years who attended the military dental clinics for one year. The prevalence of hypertension in the study population was 2.5% (3363/132,529). Following multivariate analysis, the associations between hypertension and dental parameters were lost and hypertension retained a positive association with obesity (Odds ratio (OR) = 4.2 (3.7–4.9)), diabetes mellitus (OR = 4.0 (2.9–5.7)), birth country of Western Europe vs. Israeli birth country (OR = 1.9 (1.6–2.2)), male sex (OR = 1.9 (1.6–2.2)), cardiovascular disease (OR = 1.9 (1.6–2.3)), presence of fatty liver (OR = 1.8 (1.5–2.3)), the birth country Asia vs. Israeli birth country (OR = 1.6 (1.1–2.3)), smoking (OR = 1.2 (1.05–1.4)), and older age (OR = 1.05 (1.04–1.06)). Further analysis among an age-, smoking- and sex matched sub-population (N = 13,452) also revealed that the dental parameters lost their statistically significant association with hypertension following multivariate analysis, and hypertension retained a positive association with diabetes (OR = 4.08 (2.6–6.1)), obesity (OR = 2.7 (2.4–3.2)), birth country of Western Europe vs. Israel (OR = 1.9 (1.6–2.3)), cardiovascular disease (OR = 1.8 (1.5–2.2)), fatty liver (OR = 1.7 (1.3–2.3)), high school education vs. academic (OR = 1.5 (1.3–1.8)), and low socio-economic status (SES) vs. high (OR = 1.4 (1.03–1.8)). We analyzed the associations between C-reactive protein (CRP) and dental parameters and combined the statistically significant variables to create a dental inflammation score (DIS). This crated a final model with the appropriate weights written as follows: DIS = (periodontal disease × 14) + (the number of teeth that required crowns × 11) + (missing teeth × 75). The mean DIS was 10.106 ± 25.184, and it exhibited a weak positive association with hypertension in the univariate analysis (OR = 1.011 (1.010–1.012)). Receiver operating characteristic (ROC) analysis of the DIS against hypertension produced a failed area under the curve (AUC) result (0.57 (0.56–0.58)). Moreover, the DIS also lost its statistical significance association with hypertension following multivariate analysis. We conclude that hypertension had no statistically significant nor clinically significant association with dental status. The study established a profile of the “patient vulnerable to hypertension”, which retained well-known risk factors for hypertension such as older age, male sex, smoking, diabetes, obesity, and fatty liver but not dental parameters.

scholarly journals Association between indicators of cattle density and incidence of paediatric haemolytic – uraemic syndrome (HUS) in children under 15 years of age in France between 1996 and 2001: an ecological study

2005 ◽  
Vol 134 (4) ◽  
pp. 712-718 ◽  
Author(s):  
R. HAUS-CHEYMOL ◽  
E. ESPIE ◽  
D. CHE ◽  
V. VAILLANT ◽  
H. DE VALK ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multivariate Analysis ◽  
Dairy Cattle ◽  
Poisson Regression ◽  
Haemolytic Uraemic Syndrome ◽  
Ecological Study ◽  
Univariate Analysis ◽  
Positive Association ◽  
Surveillance Data ◽  
The Past

Over the past years Shiga-like toxin-producing Escherichia coli (STEC) O157:H7 emerged as an important cause of severe gastrointestinal illnesses and haemolytic–uraemic syndrome (HUS) with up to 10% of children infected with STEC developing HUS. We conducted a geographical ecological study using the district as the statistical unit. For each district, we estimated the incidence of HUS among children <15 years for the period 1996–2001 from national HUS surveillance data and data obtained on cattle density. We used multivariate Poisson regression to quantify the relation, adjusted for covariates, between paediatric HUS incidence and exposure to cattle. In univariate analysis, a positive association was observed between several cattle-density indicators and HUS incidence. In multivariate analysis, HUS paediatric incidence was associated with dairy cattle density and the ratio of calves to children <15 years (P<0·001). Our findings are consistent with previous studies in other countries and support the recommendation to limit exposure of children to dairy cattle and manure to reduce the risk of STEC infection.

scholarly journals Relationship between Adipokines and Cardiovascular Ultrasound Parameters in Metabolic-Dysfunction-Associated Fatty Liver Disease

2021 ◽  
Vol 10 (21) ◽  
pp. 5194
Author(s):  
Abdulrahman Ismaiel ◽  
Mihail Spinu ◽  
Livia Budisan ◽  
Daniel-Corneliu Leucuta ◽  
Stefan-Lucian Popa ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Univariate Analysis ◽  
Left Ventricular ◽  
Serum Adiponectin ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Metabolic Dysfunction

(1) Background: The role of adipokines such as adiponectin and visfatin in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease remains unclear. Therefore, we aim to assess serum adiponectin and visfatin levels in MAFLD patients and associated cardiovascular parameters. (2) Methods: A cross-sectional study involving 80 participants (40 MAFLD patients, 40 controls), recruited between January and September 2020, was conducted, using both hepatic ultrasonography and SteatoTestTM to evaluate hepatic steatosis. Echocardiographic and Doppler parameters were assessed. Serum adipokines were measured using ELISA kits. (3) Results: Adiponectin and visfatin levels were not significantly different in MAFLD vs. controls. Visfatin was associated with mean carotid intima-media thickness (p-value = 0.047), while adiponectin was associated with left ventricular ejection fraction (LVEF) (p-value = 0.039) and E/A ratio (p-value = 0.002) in controls. The association between adiponectin and E/A ratio was significant in the univariate analysis at 95% CI (0.0049–0.1331, p-value = 0.035), but lost significance after the multivariate analysis. Although LVEF was not associated with adiponectin in the univariate analysis, significant values were observed after the multivariate analysis (95% CI (−1.83–−0.22, p-value = 0.015)). (4) Conclusions: No significant difference in serum adiponectin and visfatin levels in MAFLD patients vs. controls was found. Interestingly, although adiponectin levels were not associated with LVEF in the univariate analysis, a significant inversely proportional association was observed after the multivariate analysis.

scholarly journals LO010: Clinical assessment of transient ischemic attack patients for symptomatic carotid disease in the emergency department

CJEM ◽  
2016 ◽  
Vol 18 (S1) ◽  
pp. S33-S33
Author(s):  
N. Motamedi ◽  
K. Abdulaziz ◽  
M. Sharma ◽  
J.J. Perry
Keyword(s):  
Carotid Stenosis ◽  
Clinical Features ◽  
Univariate Analysis ◽  
Disease Diagnosis ◽  
Older Age ◽  
Carotid Disease ◽  
Multicenter Cohort Study ◽  
Symptomatic Carotid ◽  
History Of ◽  
Male Sex

Introduction: TIAs precede about 30% of strokes, with 4-10% having a stroke within 90 days of their TIA. In patients with a TIA due to symptomatic carotid disease, diagnosis and treatment within 2 weeks has been shown to have much better outcomes, while delay beyond 12 weeks no longer reduces subsequent stroke risk. The objective of this study was to determine the clinical findings associated with symptomatic critical disease following an ED visit for TIA to indicate patients requiring prompt carotid imaging. Methods: We performed a prospective Canadian multicenter cohort study, at 13 academic sites, of ED patients with TIA or non-disabling stroke from 2006-2014. Treating ED physicians indicate clinical features on standardized data collection forms. Symptomatic carotid disease was carotid stenosis 50-99%, or carotid dissection, adjudicated by stroke neurology to be the etiology of the index event. Patients were followed by medical review and telephone up to 90 days. Univariate analysis was conducted for clinical features associated with patients who were eventually found to have symptomatic carotid disease as a cause for their TIA. Results: The cohort included 305 patients with and 5,277 without symptomatic carotid disease. Positive predictors of symptomatic carotid disease included older age (74.0 yrs vs 68.0 yrs p<0.0001), male sex (62.9% vs 47.9%; p<0.0001), history of weakness (63.3% vs 41.4%; p<0.0001), language disturbance (52.1% vs 40.0%; p<0.0001), weakness on physical exam (25.5% vs 17.1%; p=0.0002), history of hypertension (74.8% vs 59.5%; p<0.0001), and known history of carotid stenosis (18.9% vs 3.1%; p<0.0001). Negative predictors of symptomatic carotid disease included first ever TIA (56.8% vs 68.8%; p<0.0001), history of altered sensation (39.4% vs 45.8%; p=0.0322), lightheadedness (13.0% vs 22.4%; p=0.0002), and vertigo (3.6% vs 12.7%; p<0.0001). Conclusion: TIA patients with older age, male sex, weakness, language disturbance or history of carotid stenosis need to be promptly imaged to assess for symptomatic carotid disease.

Conjunctival melanoma: Risk factors for recurrent or new tumor in 540 patients at a single ocular oncology center

2020 ◽  
pp. 112067212097039
Author(s):  
Sarangdev Vaidya ◽  
Lauren A Dalvin ◽  
Antonio Yaghy ◽  
Richard Pacheco ◽  
Jerry A Shields ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Tumor Location ◽  
Tumor Formation ◽  
Older Age ◽  
Conjunctival Melanoma ◽  
Secondary Tumor ◽  
Unit Increase ◽  
History Of

Purpose: To investigate risk factors for recurrent or new tumor in patients with conjunctival melanoma. Methods: Retrospective review of patients with conjunctival melanoma managed on the Ocular Oncology Service, Wills Eye Hospital from 1974 to 2019. Results: There were 540 patients with mean follow-up of 57.6 months, of whom 176 (33%) had recurrent or new tumor formation. Risk factors for recurrent or new tumor on univariate analysis included presentation at older age (OR: 1.02 [1.01–1.03] per 1-year increase in age, p = 0.002), history of prior conjunctival surgery (OR: 1.62 [1.05–2.49], p = 0.03), worse visual acuity at presentation (OR: 1.76 [1.04–2.98] per 1 log-unit increase, p = 0.04), more advanced AJCC clinical T-subcategory (OR: 1.08 [1.02–1.14] per 1 subcategory increase, p = 0.01), tumor primary location in tarsal conjunctiva (OR: 1.80 [1.09–2.98], p = 0.02), and secondary tumor involvement of the fornix (OR: 1.68 [1.06–2.65], p = 0.03), and eyelid (OR: 1.92 [1.07–3.43], p = 0.03). Risk factors on multivariate analysis using all demographics, clinical features, and tumor location included presentation at older age (OR: 1.02 [1.00–1.03], p = 0.01), history of prior conjunctival surgery (OR: 1.84 [1.16–2.94], p = 0.01), and more advanced AJCC clinical T-subcategory (OR: 1.07 [1.01–1.13] per one subcategory increase, p = 0.03). Conclusion: On multivariate analysis, the strongest predictors of recurrent or new tumor formation following treatment of conjunctival melanoma included older age, history of prior conjunctival surgery, and advanced AJCC T-subcategory. These results suggest that earlier detection and the first surgery in conjunctival melanoma management are critical for prevention of recurrent or new tumor, and we recommend prompt referral to an experienced surgeon.

scholarly journals Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study

2016 ◽  
Vol 26 (4) ◽  
pp. 424-429 ◽  
Author(s):  
S. Tiosano ◽  
A. Farhi ◽  
A. Watad ◽  
N. Grysman ◽  
R. Stryjer ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Multivariate Analysis ◽  
Lupus Erythematosus ◽  
Univariate Analysis ◽  
Positive Association ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Medical Database ◽  
Systemic Lupus ◽  
Cross Sectional

Aims.Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia.Method.A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel.Results.The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042).Conclusions.We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

Prognostic Factors in Nonmetastatic Ewing’s Sarcoma of Bone Treated With Adjuvant Chemotherapy: Analysis of 359 Patients at the Istituto Ortopedico Rizzoli

2000 ◽  
Vol 18 (1) ◽  
pp. 4-4 ◽  
Author(s):  
Gaetano Bacci ◽  
Stefano Ferrari ◽  
Franco Bertoni ◽  
Simonetta Rimondini ◽  
Alessandra Longhi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Chemotherapy Regimen ◽  
Univariate Analysis ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Axial Location ◽  
Male Sex

PURPOSE: The identification of prognostic factors in patients with nonmetastatic Ewing’s sarcoma could allow the use of risk-adapted therapeutic strategies of treatment. PATIENTS AND METHODS: Data on 359 patients with nonmetastatic Ewing’s sarcoma of bone treated at a single institution between January 1979 and April 1995 were retrospectively considered. The influence of clinical, hematologic, therapeutic, and histologic parameters on event-free survival was assessed. RESULTS: By univariate analysis, the following features were found to be associated with a poor prognosis: male sex (P < .02), age older than 12 years (P < .006), fever (P < .0001), anemia (P < .0025), high serum lactate dehydrogenase (LDH) level (P < .0001), axial location (P < .04), radiation therapy only for local control (P < .009), type of chemotherapy regimen (P < .0001), and poor chemotherapy-induced necrosis (P < .001). After multivariate analysis, the adverse independent prognostic factors were male sex (P < .04), age older than 12 years (P < .001), fever (P < .0002), anemia (P < .02), high serum LDH level (P < .0003), axial location (P < .02), and type of chemotherapy regimen (P < .0003). When the multivariate analysis was restricted to surgically treated patients, the adverse independent prognostic factors were poor chemotherapy-induced necrosis (P < .0001), fever (P < .015), anemia (P < .02), and high serum LDH level (P < .025). CONCLUSION: The prognosis in cases of nonmetastatic Ewing’s sarcoma is influenced by many different clinical and hematologic variables, all of which are to be considered when patients are being stratified according to the risk of relapse. In surgically treated patients, the most important prognostic factor is chemotherapy-induced necrosis.

scholarly journals Risk Factors for Mortality and Progression to Severe COVID-19 Disease in the Southeast United States (US): A Report from the SEUS Study Group

2021 ◽  
pp. 1-33 ◽  
Author(s):  
Athena L. V. Hobbs ◽  
Nicholas Turner ◽  
Imad Omer ◽  
Morgan K. Walker ◽  
Ronald M. Beaulieu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Mechanical Ventilation ◽  
Multivariate Analysis ◽  
Hospital Mortality ◽  
Mortality Risk ◽  
Severe Disease ◽  
Increased Risk ◽  
Male Sex ◽  
Southeast Us

Abstract Objective Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast US. Design, Setting, and Participants Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020 and May 8, 2020 within one of 15 participating hospitals in 5 health systems across 5 states in the Southeast US. Methods The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast US. Results A total of 502 patients were included, and the majority (476/502, 95%) had clinically evaluable outcomes. Hospital mortality was 16% (76/476), while 35% (177/502) required ICU admission, and 18% (91/502) required mechanical ventilation. By both univariate and adjusted multivariate analysis, hospital mortality was independently associated with age (adjusted odds ratio [aOR] 2.03 for each decade increase, 95% CI 1.56-2.69), male sex (aOR 2.44, 95% CI: 1.34-4.59), and cardiovascular disease (aOR 2.16, 95% CI: 1.15-4.09). As with mortality, risk of severe disease was independently associated with age (aOR 1.17 for each decade increase, 95% CI: 1.00-1.37), male sex (aOR 2.34, 95% CI 1.54-3.60), and cardiovascular disease (aOR 1.77, 95% CI 1.09-2.85). Conclusions In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast US. In-hospital mortality risk doubled with each subsequent decade of life.

scholarly journals A Population-Based Study of Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis in the United States from 2001-2015

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-48
Author(s):  
Caleb J. Smith ◽  
Gordon J. Ruan ◽  
John William Thomas ◽  
Ayalew Tefferi ◽  
Ronald S. Go ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Essential Thrombocythemia ◽  
Primary Myelofibrosis ◽  
Population Based ◽  
Incidence Rates ◽  
Monocytic Leukemia ◽  
Male Sex ◽  
Better Than

Introduction: Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF) are BCR/ABL1-negative myeloproliferative neoplasms (MPN) that are associated with morbidity and increased mortality. Limited data regarding population-based outcomes for these MPNs have been reported. Our aim was to use the Surveillance, Epidemiology, and End Results (SEER) registry to investigate population based outcomes for PV, ET, and PMF. Methods: The SEER 18 registries were used to identify patients with ICD-O-3 diagnosis codes for PV (9950/3), ET (9962/3), and PMF (9961/3) from 2001-2015. For ET and PMF, histologic diagnosis was required for inclusion. Incidence was age-adjusted to the U.S. 2000 standard population. Causes of death were obtained and MPN-related death was defined as death from any myeloid disorder (ET, PV, PMF, acute myeloid leukemia [AML], acute monocytic leukemia, other myeloid/monocytic leukemia, and aleukemic, subleukemic and NOS). Relative survival (RS) was defined as the ratio of the proportion of observed survivors in a cohort of PV, ET, PMF patients to the proportion of expected survivors in a comparable set of individuals that did not respectively have PV, ET, or PMF, adjusting for the general survival of the US population for race, sex, age, and time when the diagnosis was established. Time to leukemic transformation was calculated using the left-truncated life tables session with a 3-month latency period used to prevent misattribution. Overall survival (OS) was calculated between the date of diagnosis and the date of death, date last known to be alive, or date of the study cut-off (31 December 2018). Variables significant in univariate analysis were included in a multivariate analysis. The Kaplan-Meier method was used to calculate overall survival (OS), and Cox regression model was used to identify predictors of survival. Statistical analyses were performed using JMP version 14.0. Results: 10,988 patients with PV, 9,146 with ET, and 4,022 with PMF were identified in SEER. The median age of diagnosis (interquartile range [IQR]) was 65 years (IQR 54-76), 67 years (IQR 54-77), and 69 years (IQR 60-78) for PV, ET, and PMF respectively. Overall incidence rates (cases/100,000) were 0.86 for PV, 0.72 for ET, and 0.30 for PMF. With a median follow up (in years, 95% confidence interval [CI]) of 7.6 (7.4-7.8), 7.9 (7.8-8.2), and 7.25 (7.0-7.5), the median OS was 11.4 (11.2-11.7), 11.75 (11.3-12.0), and 3.5 (3.3-3.7), for PV, ET, and PMF respectively. RS was better than expected survival for PV and ET, while less than expected survival for PMF (Figure 1). 3853 of PV patients died (35.1%) by the end of the study period, with 4.1% and 34.1% of deaths from PV-related and cardiovascular disease respectively (Table 1). 3142 of ET patients died (34.4%), with 7.2% and 32.2% of deaths from ET-related and cardiovascular disease respectively. 2578 patients with MF died (64.1%), with 13.2%, and 51.9% of deaths from PMF-related and other malignancies respectively. 106 patients (1.0%) with PV, 135 patients (1.5%) with ET, and 127 patients (3.2%) with PMF transformed to AML. Median time to transformation was 4.8, 6.3, and 2.3 years for PV, ET, and PMF respectively. Factors indicating inferior OS on multivariate analysis (Table 2) included age ≥ 65, female sex, and year of diagnosis for PV, age ≥ 65, male sex, and year of diagnosis for ET, and age ≥ 65, and male sex for PMF. Conclusion: Incidence rates for PV, ET, and PMF were similar to previous reports. RS was better than expected survival for PV and ET, while less than expected survival for PMF. The majority of deaths in ET and PV occurred from cardiovascular disease; a finding likely related to these MPNs. Patients with PMF were more likely to die from their disease or a subsequent malignancy. Transformation to AML occurred less frequently than prior large case series, noting a limitation in the current study. Patients with PMF were more likely to transform to AML with a shorter time interval. Older age was associated with worse OS in all patients. Male sex was predictive of worse survival for ET and PMF, while female sex was associated with worse survival in PV. Over the years, survival has improved for PV and remained essentially unchanged for ET and PMF. Figure Disclosures Shah: Dren Bio: Consultancy.

Multivariate Analysis of Prognostic Factors in CLL: A Study on 431 Patients Showing Usefulness of Novel Biological and Old Clinical Parameters in Predicting Shorter Survival: An Italian Multicentric Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3143-3143
Author(s):  
Luca Laurenti ◽  
Michela Tarnani ◽  
Pietro Bulian ◽  
Gianluca Gaidano ◽  
Davide Rossi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Prognostic Model ◽  
Univariate Analysis ◽  
Absolute Lymphocyte Count ◽  
Cd38 Expression ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Male Sex

Abstract B-cell chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease with highly variable clinical courses. Recently, besides classical clinical parameters, including Rai/Binet’s staging system, novel biological factors acquired prognostic relevance especially for risk-adapted therapeutic strategies: IgVH mutational status, ZAP-70 and CD38 expression, chromosome aberration (del13q, trisomy 12, del11q, del17p) detected by FISH analysis. In a recent report, Wierda et al constructed a prognostic nomogram predictive for overall survival based on clinical and routine laboratory characteristic of 1674 CLL patients: age, beta2 microglobulin, absolute lymphocyte count, sex, Rai stage and number of involved lymph node groups. Biological prognostic features were not considered in this model but the authors concluded that “future works will focus on incorporation of new prognostic factors into this prognostic model. Actually, unlike other haematological malignancies, there is no a standard Prognostic Index that can be used to group CLL patients according clinical and new biological prognostic parameters and to guide the choice of treatment. To assess which factors give independent contribution in predicting shorter survival we collected 784 patients data from 4 laboratories. All variables were measured at diagnosis or before start of therapy; they included: age above 65 years, male sex, Rai stage &gt;0, beta2 microglobulin &gt;2.5 mg/L, absolute lymphocyte count (ALC), involvement of 3 or more nodal groups, high risk FISH cytogenetics (17p- or 11q-), IgVH mutational status, ZAP-70 and CD38 expression. Survival was measured from diagnosis until death from any cause. A sample of 431 patients was obtained after deleting cases with missing values. Median follow-up was 60 months (54–65). There were 63 deaths (15%) during follow-up, with a not reached median survival at 250 months. During follow-up 43% of patients were treated. Cox proporzional hazard model was used for univariate and multivariate analysis. P &lt;0.05 was considered to be statistically significant. Multivariate model was developed including those variables statistically significant in univariate analysis and further variables were eliminated from the final model by backward selection. IgVH, ZAP-70, CD38, ALC, male sex were not significant in univariate analysis. In multivariate analysis the following variables predicted for shorter survival (table 1): age&gt;65 years, Rai stage&gt;0, beta2&gt;2.5mg/L, high risk FISH. In a larger subset of patients (568), selected with all variables except beta2 microglobulin, the above results were confirmed, in particular no independent contribution was given by IgVH, ZAP-70 and CD38, even if they turned out significant in univariate analysis. Beta2 microglobulin and high risk FISH or only high risk FISH retained prognostic power respectively in a subset of 198 patients under 65 years of age and in a subset of 252 patients with Rai stage 0. In conclusion age&gt;65 years, B2 microglobulin&gt; 2,5 mg/L, Rai stage &gt;0, and high risk FISH abnormalities (del 17p or 11q) will be considered by clinician because of independent prognostic factor of OS. A nomogram will developed to predict for survival using the independent covariates identified in multivariate analysis. This weighted prognostic model will permit to obtain a total point score predictive for median survival of each patient, based on clinical and biological characteristic. Table 1: MULTIVARIATE ANALYSIS (COX MODEL, p = Wald test) Variables hazard ratio (confidence interval) p-value r = removed by bacward selection Age&gt;65 2.19 (1.26–3.79) 0,0052 Nodal sites involved &gt;= 3 r r Beta-2 microglobulin &gt;2.5mg/L 1.87 (1.06–3.28) 0,03 Rai stage &gt; 0 2.13 (1.26–3.62) 0,0051 FISH 17p- or 11q- 2.41 (1.42–4.08) 0,0011

The Achievement of a 3-Month Complete Cytogenetic Response (3-mo CCyR) to Second Generation (2nd) Tyrosine Kinase Inhibitors (TKI) Post Imatinib Failure Is the Only Predictive Factor for Event-Free (EFS) and Overall Survival (OS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2289-2289
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Jenny Shan ◽  
Susan O'Brien ◽  
Alfonso Quintas-Cardama ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Predictive Factor ◽  
Research Funding ◽  
Second Generation ◽  
Univariate Analysis ◽  
Response Rates ◽  
Cytogenetic Response ◽  
Older Age ◽  
Imatinib Therapy ◽  
Factors Associated

Abstract Abstract 2289 2nd TKIs such as dasatinib and nilotinib have shown significant activity post imatinib failure, with high rates of hematologic and cytogenetic responses. Achieving early cytogenetic response is a known major determinant of outcome in patients (pts) treated with imatinib. In a previous report from our institution, we reported that the achievement of a previous cytogenetic response to imatinib therapy is a major predictive factor in pts receiving a 2nd TKI. The aim of our study was to assess the impact of a 3-mo CCyR on EFS and OS of pts treated with 2nd TKI post imatinib failure. 123 pts with chronic phase (CP) CML after imatinib failure were treated with dasatinib (n=78) or nilotinib (n=45). Median age was 56 years (range, 21–83). Median duration of CP (CML diagnosis to start of second generation TKI) was 67 months (range, 2–268). Their best response to imatinib was complete hematologic response (CHR) only in 24%, and cytogenetic response in 63% (28% complete, 17% partial, 18% minor). The CHR rates were 87% and 84% in pts treated with dasatinib and nilotinib, respectively (p=0.75). The major cytogenetic response rates were 64% and 62% (p=0.85), and the complete cytogenetic response rates were 60% and 56% (p=0.70). The rates of cytogenetic response at 3-, 6- and 12-mo were 59%, 63% and 69% (p=0.39) and 60%, 55% and 51% (p= 0.7) in pts treated with dasatinib and nilotinib, respectively, and the rates of CCyR at these same time-points were 32%, 41% and 48% (p= 0.13) and 36%, 36% and 35% (p= 0.99), respectively. The 3-year EFS and OS rates were 53% and 84%, respectively. Factors associated with poor EFS in the univariate were older age (> 55 years), lack of any cytogenetic response to previous imatinib therapy, more than ≥90% Philadelphia-positive metaphases (Ph) at the start of 2nd TKI therapy, and lack of a 3-mo CCyR to 2nd TKI therapy. In a multivariate analysis, the lack of a 3-mo CCyR to 2nd TKI therapy (HR= 4.5; p<0.001) was selected as the only independent factor associated with poor EFS, with a 3-year EFS rates of 74% and 43% for pts with and without 3-mo CCyR, respectively. Factors associated with poor OS in the univariate analysis were older age (>55 years), increasing marrow blasts, lack of any cytogenetic response to previous imatinib therapy, and lack of a 3-mo CCyR to 2nd TKI therapy. In a multivariate analysis, only a lack of a 3-mo CCyR to 2nd TKI therapy (HR=5.4; p = 0.03) was independently associated with a lower probability of survival; the 3-year OS rates were 98% and 79% for pts with and without 3-mo CCyR, respectively. Therefore we analyzed factors that were associated with the 3-mo achievement of a CCyR. In the univariate analysis, high hemoglobin level, previous cytogenetic response to imatinib therapy, and ≤90% Ph, and increasing marrow blast% were associated with the achievement of a CCyR at 3 months of therapy with 2nd TKI. In the subsequent multivariate analysis for response, Ph% >90 and Hgb <12.0 were independent poor predictive factor for 3-mo CCyR. In conclusion, the achievement of a 3-mo CCyR is the only predictor of outcome in pts treated with 2nd TKI post imatinib failure. Pts with high tumor burden (defined Ph >90%) and anemia (Hgb< 12.0) have a low likelihood of achieving a 3-mo CCyR to 2nd TKI therapy and therefore should be offered additional options. Disclosures: Jabbour: BMS: Honoraria; Novartis: Honoraria. Cortes: Novartis: Research Funding; BMS: Consultancy; Pfizer: Consultancy, Research Funding.

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