scholarly journals Morphological Features and Prognostic Significance of ARID1A-Deficient Esophageal Adenocarcinomas

2017 ◽  
Vol 141 (7) ◽  
pp. 970-977 ◽  
Author(s):  
Michael G. Drage ◽  
Mingkhwan Tippayawong ◽  
Agoston T. Agoston ◽  
Yifan Zheng ◽  
Raphael Bueno ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Nodal Metastasis ◽  
Cox Proportional Hazards ◽  
Barrett Esophagus ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Increased Risk ◽  
Primary Driver

Context.— The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. Objective.— To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. Design.— One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus–associated dysplasia, when feasible. Associations between categorical clinicopathologic variables were analyzed by Fisher exact test, and survival analysis was performed by a Cox proportional hazards analysis. Results.— The study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120 EACs (43%) and showed no correlation with ARID1A deficiency (P > .05). MLH1 loss was present in only 2 of 120 EACs (2%); both of which were also deficient in ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal metastasis but had no effect on overall patient survival. Conclusions.— ARID1A-deficient EACs show a phenotype similar to colon cancer with high microsatellite instability but do not appear to have any prognostic significance. Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs.

Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

Prognostic significance of positive lymph nodes in carcinoma of the cervix following radical hysterectomy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5538-5538
Author(s):  
O. K. Macdonald ◽  
C. M. Lee ◽  
J. Chen ◽  
M. Dodson ◽  
D. K. Gaffney
Keyword(s):  
Radical Hysterectomy ◽  
Proportional Hazards ◽  
Large Population ◽  
Prognostic Significance ◽  
Median Number ◽  
Nodal Metastasis ◽  
Cox Proportional Hazards ◽  
Population Database ◽  
Chi Square ◽  
Primary Surgery

5538 Background: Lymph node (LN) metastases portend a poor outcome in women with carcinoma of the uterine cervix, but little data quantitatively evaluate nodal metastasis in relation to prognosis. We queried a large population database to analyze the number of positive LN in relation to survival following radical hysterectomy and lymphadenectomy. Methods: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) Program on women who had primary surgery for the years 1988–2003 (n = 4,559). Analyses using the chi-square test and Cox proportional hazards regression were performed. Exploratory analysis revealed equivalent statistical outcomes in each group for 0 (n = 3,715), 1–2 (n = 552), 3–9 (n = 261), and ≥10 (n = 31) positive LNs, respectively. Results: The median number of LNs removed per patient has significantly declined in recent years (median = 21 for 1988–1998, median = 18 1998–2003, p=.003). The 5-year rates of cause specific (CSS) and overall survival (OS) were 94% and 91%, 76% and 69%, 62% and 58%, and 41% and 35% for 0, 1–2, 3–9 and ≥10 positive LNs, respectively. Favorable stage and grade predicted for survival on multivariate analysis. Adenocarcinoma histology predicted significantly inferior CSS (p=.007) and OS (p=.01) compared to squamous histology in women with positive LNs, but predicted improved OS (p=.004) in women with LN negative disease. An increasing number of LNs removed significantly benefited OS (p=.001). The strongest predictors for both CSS and OS were ≥10 positive LN (HR 1.8 CI 1.2–2.7, p<.0001) a positive LN ratio >25% (HR 1.8 CI 1.5–2.2, p<.0001) and paraaortic LN metastasis (HR 2.1 CI 1.6–2.8, p<.0001). Conclusions: The extent of lympadenectomy has declined since 1988 within the SEER. LN positive disease in carcinoma of the cervix portends a prognosis that is inversely proportional to the number of involved nodes. Adenocarcinoma histology predicted for a more aggressive or benign phenotype depending on LN status. A positive LN ratio >25% demonstrated diminished survival suggesting that the quantitative LN burden is predictive of prognosis. Nodal involvement of the paraaortic region remains a strong indicator of mortality. No significant financial relationships to disclose.

Impact of anemia on hospitalization and mortality in older adults

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3841-3846 ◽  
Author(s):  
Bruce F. Culleton ◽  
Braden J. Manns ◽  
Jianguo Zhang ◽  
Marcello Tonelli ◽  
Scott Klarenbach ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Normal Kidney ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Community Dwelling Older Adults

Although anemia is common in older adults, its prognostic significance is uncertain. A total of 17 030 community-dwelling subjects 66 years and older were identified between July 1 and December 31, 2001, and followed until December 31, 2004. Cox proportional hazards analyses were performed to determine the associations between anemia (defined as hemoglobin < 110 g/L) and hemoglobin and all-cause mortality, all-cause hospitalization, and cardiovascular-specific hospitalization. Overall, there were 1983 deaths and 7278 first hospitalizations. In patients with normal kidney function, adjusting for age, sex, diabetes mellitus, and comorbidity, anemia was associated with an increased risk for death (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.55-5.12), first all-cause hospitalization (HR, 2.16; 95% CI, 1.88-2.48), and first cardiovascular-specific hospitalization (HR, 2.49; 95% CI, 1.99-3.12). An inverse J-shaped relationship between hemoglobin and all-cause mortality was observed; the lowest risk for mortality occurred at hemoglobin values between 130 to 150 g/L for women and 140 to 170 g/L for men. Anemia is associated with an increased risk for hospitalization and death in community-dwelling older adults. Consideration should be given to redefine “normal” hemoglobin values in the elderly. Clinical trials are also necessary to determine whether anemia correction improves quality or quantity of life in this population.

Abstract P087: Goldberger's Electrocardiographic Criteria For Left Ventricular Dysfunction Associated With Increased Mortality

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Kang Rui Xiang ◽  
Elsayed Z Soliman ◽  
Prashant Bhave ◽  
Matthew J Singleton
Keyword(s):  
Left Ventricular Dysfunction ◽  
Cardiovascular Mortality ◽  
Ventricular Dysfunction ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Poor Outcomes

Goldberger’s Electrocardiographic Criteria for Left Ventricular Dysfunction Associated with Increased Mortality Introduction: The ability of the Goldberger electrocardiographic (ECG) triad criteria to detect left ventricular dysfunction (LVD) is well-established. However, the prognostic significance of this triad as a predictor of poor outcomes is not known. Hypothesis: We hypothesized that the Goldberger ECG-LVD triad is associated with increased all-cause mortality and cardiovascular mortality in the general population. Methods: This analysis included 8,426 participants (60.5 ± 13.6 years, 51.5% women, 50% non-Hispanic white) from the Third National Health and Nutrition Examination Survey. The Goldberger ECG-LVD triad was defined as follows: high precordial QRS voltage (SV1 or SV2 + RV5 or RV6 ≥3500 μV); low limb lead QRS voltage (mean QRS amplitude in each of the limb leads ≤ 800 μV); and poor R wave progression (RV4/SV4 <1). Mortality was ascertained using the National Death Index. Results: At baseline, 1,384 (47.3%) of the participants had at least one of the criteria of Goldberger triad (1,193 had only one and 191 participants had 2 or more). During a median follow up of 13.8 years, 3,184 deaths occurred, of which 1,405 were cardiovascular. In multivariable-adjusted Cox proportional hazards models, presence of at least one of the Goldberger triad criteria (vs. none) was associated with increased risk of all-cause (HR 1.17, 95% CI 1.08 – 1.26, p = <0.0001) and cardiovascular mortality (1.19, 1.06 – 1.33, p = 0.003). Conclusion: The Goldberger ECG-LVD triad for left ventricular dysfunction is associated with increased all-cause and cardiovascular mortality and may offer prognostic value, in addition to its diagnostic utility.

scholarly journals Prognostic value of fibrinogen to albumin ratios among critically ill patients with acute kidney injury

2021 ◽  
Author(s):  
Wenkai Xia ◽  
Chenyu Li ◽  
Xiajuan Yao ◽  
Yan Chen ◽  
Yaoquan Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hospital Mortality ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Proportional Hazards ◽  
Predictive Accuracy ◽  
Prognostic Significance ◽  
Kidney Injury ◽  
Cox Proportional Hazards ◽  
Increased Risk

AbstractFibrinogen to albumin ratios (FAR) have shown to be a promising prognostic factor for improving the predictive accuracy in various diseases. This study explores FAR's prognostic significance in critically ill patients with acute kidney injury (AKI). All clinical data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.4. All patients were divided into four groups based on FAR quartiles. The primary endpoint was in-hospital mortality. A generalized additive model was applied to explore a nonlinear association between FAR and in-hospital mortality. The Cox proportional hazards models were used to determine the association between FAR and in-hospital mortality. A total of 5001 eligible subjects were enrolled. Multivariate analysis demonstrated that higher FAR was an independent predictor of in-hospital mortality after adjusting for potential confounders (HR, 95% CI 1.23, 1.03–1.48, P = 0.025). A nonlinear relationship between FAR and in-hospital mortality was observed. FAR may serve as a potential prognostic biomarker in critically patients with AKI and higher FAR was associated with increased risk of in-hospital mortality among these patients.

Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

2021 ◽  
pp. 000486742110096
Author(s):  
Oleguer Plana-Ripoll ◽  
Patsy Di Prinzio ◽  
John J McGrath ◽  
Preben B Mortensen ◽  
Vera A Morgan
Keyword(s):  
Confidence Interval ◽  
Western Australia ◽  
Urban Areas ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Indigenous Status ◽  
Increased Risk ◽  
The Relationship ◽  
Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Towards refining WCRF/AICR cancer prevention recommendations for red and processed meat intake: Insights from Alberta’s Tomorrow Project cohort

2021 ◽  
pp. 1-38
Author(s):  
Ala Al Rajabi ◽  
Geraldine Lo Siou ◽  
Alianu K. Akawung ◽  
Kathryn L McDonald ◽  
Tiffany R. Price ◽  
...  
Keyword(s):  
Cancer Prevention ◽  
Proportional Hazards ◽  
Red Meat ◽  
Cox Proportional Hazards ◽  
Processed Meat ◽  
Carcinogenic Effect ◽  
Meat Intake ◽  
Increased Risk ◽  
Red Meats ◽  
Red And Processed Meat

ABSTRACT Current cancer prevention recommendations advise limiting red meat intake to <500g/week and avoiding consumption of processed meat, but do not differentiate the source of processed meat. We examined the associations of processed meat derived from red vs. non-red meats with cancer risk in a prospective cohort of 26,218 adults who reported dietary intake using the Canadian Diet History Questionnaire. Incidence of cancer was obtained through data linkage with Alberta Cancer Registry with median (IQR) follow-up of 13.3 (5.1) years. Multivariable Cox proportional hazards regression models were adjusted for covariates and stratified by age and gender. The median (IQR) consumption (g/week) of red meat, processed meat from red meat and processed meat from non-red meat were 267.9 (269.9), 53.6 (83.3), and 11.9 (31.8), respectively. High intakes (4th Quartile) of processed meat from red meat was associated with increased risk of gastro-intestinal cancer Adjusted Hazard Ratio (AHR) (95% CI): 1.68 (1.09 – 2.57) and colorectal cancers AHR (95% CI): 1.90 (1.12 – 3.22), respectively in women. No statistically significant associations were observed for intakes of red meat or processed meat from non-red meat. Results suggests that the carcinogenic effect associated with processed meat intake may be limited to processed meat derived from red meats. The findings provide preliminary evidence toward refining cancer prevention recommendations for red and processed meat intake.

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

scholarly journals Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients

2021 ◽  
Vol 14 ◽  
pp. 175628482199735
Author(s):  
Steven Deitelzweig ◽  
Allison Keshishian ◽  
Amiee Kang ◽  
Amol D. Dhamane ◽  
Xuemei Luo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Proportional Hazards ◽  
Bleeding Event ◽  
Cox Proportional Hazards ◽  
High Rate ◽  
Gi Bleeding ◽  
Increased Risk ◽  
Gi Bleed

Background: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. Methods: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services ( CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. Results: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42–1.74], major bleeding (HR: 2.79, 95% CI: 2.64–2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23–1.36) than patients without a major GI bleed. Conclusion: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.

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