Neutrophil extracellular traps (NETs) and thrombosis (Thr) in pancreaticobiliary cancer (PBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16230-e16230
Author(s):  
Christos Fountzilas ◽  
Han Yu ◽  
Anm Nazmul Khan ◽  
Thejaswini Giridharan ◽  
Alok A. Khorana ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Stage Iv ◽  
Information Criterion ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Specific Marker ◽  
Patients At Risk ◽  
Poor Outcomes

e16230 Background: NETs are linked to tissue damage, Thr and cancer progression. Detection of NETs in pancreatic cancer (PC) tissue and NET products in plasma, such as citrullinated Histone 3 (cit-H3) and myeloperoxidase (MPO), can predict survival. A robust biomarker to identify PC patients that may benefit from prophylactic antithrombotic interventions is still lacking. We hypothesized that NET products can predict PC patients at risk of poor outcomes. Methods: Frozen plasma collected on diagnosis from a cohort of 117 patients with HPBC (69% with PC) with known tissue factor (TF) levels was analyzed for MPO and cit-H3 by ELISA. Plasma MPO is a marker of neutrophil degranulation while cit-H3 is a more specific marker of NETosis. Univariate association of clinical variables, TF, cit-H3, MPO with overall survival (OS) was performed. For multivariable analysis, Cox proportional hazards regression model and backward stepwise selection based on the Bayesian information criterion (BIC) were used. Results: We observed a strong correlation between MPO and cit-H3. MPO also correlated with TF. Only TF showed a trend with association with the risk of Thr (p=0.053). Results of the multivariable model for OS are presented in the table (all patients and stratified by Thr status). High absolute neutrophil count (ANC) predicted worse OS only in patients without Thr. Increased cit-H3 was associated with worse OS. Higher MPO predicted worse OS in stage IV patients, which is in contrast to their relationship in stage I-III patients, where increased MPO was associated with improved OS. This interaction effect is stronger in patients with thrombosis. Conclusions: Plasma cit-H3, a systemic marker of NETosis, was associated with worse OS in PBC. Significant MPO by stage interaction implies a differential association of MPO with the OS among patients in different cancer stages. The activation status of neutrophils, including degranulation and NETosis, may be an important predictive biomarker for OS in patients with HPBC with interactions with both stage and Thr. Prospective studies to confirm and extend our findings are ongoing.[Table: see text]

Reporting of Multivariable Methods in the Medical Literature

2008 ◽  
Vol 56 (7) ◽  
pp. 954-957 ◽  
Author(s):  
Jeanette M. Tetrault ◽  
Maor Sauler ◽  
Carolyn K. Wells ◽  
John Concato
Keyword(s):  
Logistic Regression ◽  
New England ◽  
Proportional Hazards ◽  
Medical Literature ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Primary Method ◽  
Primary Analysis ◽  
Proportional Hazards Assumption ◽  
Complete Reporting

BackgroundMultivariable models are frequently used in the medical literature, but many clinicians have limited training in these analytic methods. Our objective was to assess the prevalence of multivariable methods in medical literature, quantify reporting of methodological criteria applicable to most methods, and determine if assumptions specific to logistic regression or proportional hazards analysis were evaluated.MethodsWe examined all original articles in Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine, from January through June 2006. Articles reporting multivariable methods underwent a comprehensive review; reporting of methodological criteria was based on each article's primary analysis.ResultsAmong 452 articles, 272 (60%) used multivariable analysis; logistic regression (89 [33%] of 272) and proportional hazards (76 [28%] of 272) were most prominent. Reporting of methodological criteria, when applicable, ranged from 5% (12/265) for assessing influential observations to 84% (222/265) for description of variable coding. Discussion of interpreting odds ratios occurred in 13% (12/89) of articles reporting logistic regression as the primary method and discussion of the proportional hazards assumption occurred in 21% (16/76) of articles using Cox proportional hazards as the primary method.ConclusionsMore complete reporting of multivariable analysis in the medical literature can improve understanding, interpretation, and perhaps application of these methods.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković
Keyword(s):  
Hodgkin Lymphoma ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Relative Dose Intensity ◽  
Cox Proportional Hazards Models ◽  
Stage Disease ◽  
Stage Iv Disease

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

scholarly journals Radiation Therapy for Retroperitoneal Sarcomas: Influences of Histology, Grade, and Size

Sarcoma ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jennifer L. Leiting ◽  
John R. Bergquist ◽  
Matthew C. Hernandez ◽  
Kenneth W. Merrell ◽  
Andrew L. Folpe ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Preoperative Radiation ◽  
High Grade ◽  
Curative Intent ◽  
Kaplan Meier ◽  
Retroperitoneal Sarcomas ◽  
Ajcc Staging

Perioperative radiation therapy (RT) has been associated with reduced local recurrence in patients with retroperitoneal sarcomas (RPS); however, selection criteria remain unclear. We hypothesized that perioperative RT would improve survival in patients with RPS and would be associated with pathological factors. The National Cancer Database (NCDB) from 2004 to 2012 was reviewed for patients with nonmetastatic RPS undergoing curative intent resection. Tumor size was dichotomized at 15 cm based on 8th edition American Joint Committee on Cancer (AJCC) staging. Patients with the highest comorbidity score were excluded. Unadjusted Kaplan–Meier and adjusted Cox proportional hazards modeling analyzed overall survival (OS). Multivariable logistic regression modeled margin positivity. A total of 2,264 patients were included; 727 patients (32.1%) had perioperative radiation in whom 203 (9.0%) had radiation preoperatively. Median (IQR) RPS size was 17.5 [11.0–27.0] cm. Histopathology was high grade in 1048 patients (43.7%). Multivariable analysis revealed that perioperative radiation was independently associated with decreased mortality (HR 0.72, 95% confidence intervals (CIs) 0.62–0.84,p<0.001), and preoperative RT was associated with reduced margin positivity (HR 0.72, 95% CI 0.53–0.97,p=0.032). Stratified survival analysis showed that radiation was associated with prolonged median OS for RPS that were high-grade (64.3 vs. 43.6 months,p<0.001), less than 15 cm (104.1 vs. 84.2 months,p=0.007), and leiomyosarcomatous (104.8 vs. 61.8 months,p<0.001). Perioperative radiation is independently associated with decreased mortality in patients with high-grade, less than 15 cm, and leiomyosarcomatous tumors. Preoperative radiation is independently associated with margin-negative resection. These data support the selective use of perioperative radiation in the multidisciplinary management of RPS.

scholarly journals 2625. Incidence of Bronchiolitis Requiring Hospitalization in the First 2 years of Life Among Healthy Term Infants with Different Races/Ethnicities: A Population-based Longitudinal Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S914-S915
Author(s):  
Kengo Inagaki ◽  
Chad Blackshear ◽  
Charlotte V Hobbs
Keyword(s):  
New York ◽  
Socioeconomic Status ◽  
Proportional Hazards ◽  
New York State ◽  
Multivariable Analysis ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Indigenous Populations ◽  
Term Infants ◽  
Race Ethnicity

Abstract Background Race/ethnicity is currently not considered a risk factor for bronchiolitis, except for indigenous populations in western countries. We sought to determine the incidence of hospitalization with bronchiolitis among different races/ethnicities, because such information can lead to more tailored preventive care. Methods We performed a population-based longitudinal observational study using the State Inpatient Database from New York state. Infants born between 2009 and 2013 at term without comorbidities were followed for the first 2 years of life, up to 2015. We calculated incidence among different race/ethnicity groups, and evaluated risks by developing Cox proportional hazards regression models. Results Of 877,465 healthy term infants, 10 356 infants were hospitalized with bronchiolitis. Overall, incidence was 11.8 per 1,000 births. Substantial difference in infants born in different seasons was observed (Figure 1). The incidence in non-Hispanic white, non-Hispanic black, Hispanic, and Asian infants was 8.6, 15.4, 19.1, and 6.5 per 1,000 births, respectively (table). On multivariable analysis adjusting for socioeconomic status, the risks remained substantially high among non-Hispanic black (hazard ratio [HR] 1.42, 95% confidence interval [CI]: 1.34–1.51) and Hispanic infants (HR 1.77, 95% CI: 1.67–1.87), particularly beyond 2–3 months of age, whereas Asian race was protective (HR 0.62, 95% CI: 0.56–0.69) (Figure 2, 3). Conclusion The risks of bronchiolitis hospitalization in the first 2 years of life was substantially higher among infants with non-Asian minority infants, particularly beyond 2–3 months of age. Further research efforts to identify effective public health interventions in each race/ethnic groups with varied socioeconomic status, such as improvement in access to care and anticipatory guidance, is warranted to overcome health disparity. Disclosures All authors: No reported disclosures.

scholarly journals Racial/ethnic disparities in the risk of intracerebral hemorrhage recurrence

Neurology ◽  
2019 ◽  
Vol 94 (3) ◽  
pp. e314-e322 ◽  
Author(s):  
Audrey C. Leasure ◽  
Zachary A. King ◽  
Victor Torres-Lopez ◽  
Santosh B. Murthy ◽  
Hooman Kamel ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Ethnic Groups ◽  
Proportional Hazards ◽  
Private Insurance ◽  
Multivariable Analysis ◽  
Ethnic Disparities ◽  
Cox Proportional Hazards ◽  
Risk Of Recurrence ◽  
Asian Patients ◽  
Racial Ethnic

ObjectiveTo estimate the risk of intracerebral hemorrhage (ICH) recurrence in a large, diverse, US-based population and to identify racial/ethnic and socioeconomic subgroups at higher risk.MethodsWe performed a longitudinal analysis of prospectively collected claims data from all hospitalizations in nonfederal California hospitals between 2005 and 2011. We used validated diagnosis codes to identify nontraumatic ICH and our primary outcome of recurrent ICH. California residents who survived to discharge were included. We used log-rank tests for unadjusted analyses of survival across racial/ethnic groups and multivariable Cox proportional hazards regression to determine factors associated with risk of recurrence after adjusting for potential confounders.ResultsWe identified 31,355 California residents with first-recorded ICH who survived to discharge, of whom 15,548 (50%) were white, 6,174 (20%) were Hispanic, 4,205 (14%) were Asian, and 2,772 (9%) were black. There were 1,330 recurrences (4.1%) over a median follow-up of 2.9 years (interquartile range 3.8). The 1-year recurrence rate was 3.0% (95% confidence interval [CI] 2.8%–3.2%). In multivariable analysis, black participants (hazard ratio [HR] 1.22; 95% CI 1.01–1.48; p = 0.04) and Asian participants (HR 1.29; 95% CI 1.10–1.50; p = 0.001) had a higher risk of recurrence than white participants. Private insurance was associated with a significant reduction in risk compared to patients with Medicare (HR 0.60; 95% CI 0.50–0.73; p < 0.001), with consistent estimates across racial/ethnic groups.ConclusionsBlack and Asian patients had a higher risk of ICH recurrence than white patients, whereas private insurance was associated with reduced risk compared to those with Medicare. Further research is needed to determine the drivers of these disparities.

scholarly journals Risk Factors for Adverse Events in Household Contacts Prescribed Preventive Treatment for Drug-resistant Tuberculosis Exposure

2020 ◽  
Author(s):  
Amyn A Malik ◽  
Mercedes C Becerra ◽  
Timothy L Lash ◽  
Lisa M Cranmer ◽  
Saad B Omer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Preventive Treatment ◽  
Cox Proportional Hazards ◽  
Drug Resistant ◽  
Event Analysis ◽  
Crude Odds Ratio ◽  
Household Contacts

Abstract Background Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan. Methods The primary outcome was development of any clinical AE during preventive treatment. Adverse events were categorized using the AE grading tables of the National Institutes of Health. Time-to-event analysis with Kaplan-Meier curves and Cox proportional hazards models accounting for recurrence were used to analyze associated risk factors. Results Of the 172 household contacts on preventive treatment, 36 (21%) developed 64 AEs during 813 months of treatment. The incidence of AEs over 6 months of treatment was 7.9 per 100 person-months; 16 per 100 person-months with a fluoroquinolone and ethionamide, and 4.4 per 100 person-months with a fluoroquinolone and ethambutol. There were 53 (83%) grade 1 and 11 grade 2 AEs, with no grade 3 or 4 AEs. In multivariable analysis, the risk of AEs was higher in contacts prescribed ethionamide as compared to ethambutol adjusting for age, sex, and body mass index (adjusted hazard ratio, 2.1 [95% confidence interval {CI}, 1.2–3.6]). Overall, there was no notable difference in treatment completion among the contacts who experienced an AE and those who did not (crude odds ratio, 1.1 [95% CI, .52–2.5]). Conclusions A fluoroquinolone-based preventive treatment regimen for drug-resistant TB exposure is well tolerated. Regimens with ethionamide are more likely to result in AEs.

scholarly journals Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew T. Carr ◽  
Camille J. Hochheimer ◽  
Andrew K. Rock ◽  
Alper Dincer ◽  
Lakshmi Ravindra ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Medical Center ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Individual Characteristic ◽  
Prior History ◽  
Central Nervous System Tumor ◽  
Medical Conditions ◽  
Characteristic Analysis ◽  
History Of

AbstractGlioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24–5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09–3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95–5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02–4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11–3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses.

scholarly journals Prognostic value of pretreatment circulating neutrophils, monocytes, and lymphocytes on outcomes in lung stereotactic body radiotherapy

2016 ◽  
Vol 23 (4) ◽  
pp. 362 ◽  
Author(s):  
M. Giuliani ◽  
L.R. Sampson ◽  
O. Wong ◽  
J. Gay ◽  
L.W. Le ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Stereotactic Body Radiotherapy ◽  
Proportional Hazards ◽  
Complete Blood Count ◽  
Multivariable Analysis ◽  
Primary Lung Cancer ◽  
Cox Proportional Hazards ◽  
T Stage ◽  
Lung Sbrt ◽  
Monocytes And Lymphocytes

PurposeIn the present study, we determined the association of pretreatment circulating neutrophils, monocytes, and lymphocytes with clinical outcomes after lung stereotactic body radiotherapy (sbrt).Methods All patients with primary lung cancer and with a complete blood count within 3 months of lung sbrt from 2005 to 2012 were included. Overall survival (os) was calculated using the Kaplan–Meier method. Factors associated with os were investigated using univariable and multivariable Cox proportional hazards regression. Fine–Gray competing risk regression was performed to test the association of the neutrophil:lymphocyte (nlr) and monocyte:lymphocyte (mlr) ratios with two types of failure: disease-related failure and death, and death unrelated to disease.Results Of the 299 sbrt patients identified, 122 were eligible for analysis. The median and range of the nlr and mlr were 3.0 (0.3–22.0) and 0.4 (0.1–1.9) respectively. On multivariable analysis, sex (p = 0.02), T stage (p = 0.04), and nlr (p < 0.01) were associated with os. On multivariable analysis, T stage (p < 0.01) and mlr (p < 0.01) were associated with disease-related failure; mlr (p = 0.03), nlr (p < 0.01), and sbrt dose of 48 Gy in 4 fractions (p = 0.03) and 54 Gy or 60 Gy in 3 fractions (p = 0.02) were associated with disease-unrelated death. Median survival was 4.3 years in the nlr≤3 group (95% confidence interval: 3.5 to not reached) and 2.5 years in the nlr>3 group (95% confidence interval: 1.7 to 4.8; p < 0.01).Conclusions In lung sbrt patients, nlr and mlr are independently associated with os and disease-unrelated death. If validated, nlr and mlr could help to identify patients who would benefit most from sbrt.

scholarly journals Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile

2020 ◽  
Vol 7 (2) ◽  
pp. MMT43
Author(s):  
Alexandra Ikeguchi ◽  
Michael Machiorlatti ◽  
Sara K Vesely
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Demographic Factors ◽  
Cox Proportional Hazards ◽  
Adjuvant Immunotherapy ◽  
Node Positive ◽  
Melanoma Patients ◽  
The Impact

Background: Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. Materials & methods: We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan–Meier method and Cox proportional hazards models. Results: All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Conclusion: Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.

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