Multivitamin Use and Risk of Stroke Mortality

Background and Purpose— An effect of multivitamin supplement on stroke risk is uncertain. We aimed to examine the association between multivitamin use and risk of death from stroke and its subtypes. Methods— A total of 72 180 Japanese men and women free from cardiovascular diseases and cancers at baseline in 1988 to 1990 were followed up until December 31, 2009. Lifestyles including multivitamin use were collected using self-administered questionnaires. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of total stroke and its subtypes in relation to multivitamin use. Results— During a median follow-up of 19.1 years, we identified 2087 deaths from stroke, including 1148 ischemic strokes and 877 hemorrhagic strokes. After adjustment for potential confounders, multivitamin use was associated with lower but borderline significant risk of death from total stroke (HR, 0.87; 95% confidence interval, 0.76–1.01), primarily ischemic stroke (HR, 0.80; 95% confidence interval, 0.63–1.01), but not hemorrhagic stroke (HR, 0.96; 95% confidence interval, 0.78–1.18). In a subgroup analysis, there was a significant association between multivitamin use and lower risk of mortality from total stroke among people with fruit and vegetable intake <3 times/d (HR, 0.80; 95% confidence interval, 0.65–0.98). That association seemed to be more evident among regular users than casual users. Similar results were found for ischemic stroke. Conclusions— Multivitamin use, particularly frequent use, was associated with reduced risk of total and ischemic stroke mortality among Japanese people with lower intake of fruits and vegetables.

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One-Year Risk of Recurrent Stroke and Death Associated with Vertebrobasilar Artery Stenosis and Occlusion in a Cohort of 10,515 Patients

Cerebrovascular Diseases ◽

10.1159/000495418 ◽

2019 ◽

Vol 47 (1-2) ◽

pp. 40-47 ◽

Cited By ~ 3

Author(s):

Adnan I. Qureshi ◽

Mushtaq H. Qureshi ◽

Li-Ming Lien ◽

Jiunn-Tay Lee ◽

Jiann-Shing Jeng ◽

...

Keyword(s):

Ischemic Stroke ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Recurrent Stroke ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Large Artery ◽

Stroke Registry ◽

Risk Of Death ◽

Vertebrobasilar Artery

Background: The natural history of vertebrobasilar artery (VBA) stenosis or occlusion remains understudied. Methods: Patients with diagnosis of ischemic stroke or transient ischemic attack (TIA) who were noted to have VBA stenosis based on computed tomography or magnetic resonance imaging or catheter-based angiogram were selected from Taiwan Stroke Registry. Cox proportional hazards model was used to determine the hazards ratio (HR) of recurrent stroke and death within 1 year of index event in various groups based on severity of VBA stenosis (none to mild: 0–49%; moderate to severe: 50–99%: occlusion: 100%) after adjusting for differences in demographic and clinical characteristics between groups at baseline evaluation. Results: None to mild or moderate to severe VBA stenosis was diagnosed in 6972 (66%) and 3,137 (29.8%) among 10,515 patients, respectively, and occlusion was identified in 406 (3.8%) patients. Comparing with patients who showed none to mild stenosis of VBA, there was a significantly higher risk of recurrent stroke (HR 1.21, 95% CI 1.01–1.45) among patients with moderate to severe VBA stenosis. There was a nonsignificantly higher risk of recurrent stroke (HR 1.49, 95% CI 0.99–2.22) and significantly higher risk of death (HR 2.21, 95% CI 1.72–2.83), among patients with VBA occlusion after adjustment of potential confounders. Conclusions: VBA stenosis or occlusion was relatively prevalent among patients with TIA or ischemic stroke and associated with higher risk of recurrent stroke and death in patients with ischemic stroke or TIA who had large artery atherosclerosis.

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Abstract WP312: The Association of Chronic Kidney Disease (CKD) With 30-day and 1-year Post Ischemic Stroke Mortality and Rehospitalization: Get With the Guidelines (GWTG) Stroke

Stroke ◽

10.1161/str.47.suppl_1.wp312 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Nada El Husseini ◽

Gregg C Fonarow ◽

Eric E Smith ◽

Christine Ju ◽

Lee H Schwamm ◽

...

Keyword(s):

Ischemic Stroke ◽

Hospital Mortality ◽

Proportional Hazards ◽

Reference Group ◽

Cox Proportional Hazards ◽

Fee For Service ◽

Stroke Mortality ◽

Medicare Beneficiaries ◽

Cox Proportional Hazards Models ◽

Ckd Stage

Background: The extent to which CKD is associated with 30-day and 1-year post ischemic stroke mortality and rehospitalization rates has not been well studied. Methods: Data from 232,236 fee for service Medicare patients admitted with ischemic stroke to 1581 AHA GWTG-Stroke participating hospitals between January 2009 and December 2012 were analyzed. Estimated GFR in mL/min/1.73 m2 was determined based on the MDRD study equation categorized as: no CKD (GFR ≥60); stage 3a CKD (GFR 45-59); stage 3b CKD (GFR 30-44); stage 4 CKD, (GFR 15-29); stage 5 CKD (GFR <15 excluding those on dialysis). Dialysis was identified by ICD-9 codes. Multivariable Cox proportional hazards models adjusted for demographics, medical history, NIHSS, arrival hour, and hospital characteristics were used to determine the independent associations of CKD (reference group those without CKD) with mortality and readmission at 30 days and 1 year. Results: After adjustment, 30-days poststroke mortality was highest among those with CKD stage 5 (HR 1.94, 95%CI 1.72-2.18), even after excluding in-hospital mortality and patients discharged to hospice (HR 2.09, 95%CI 1.66-2.63). Unadjusted 1-year mortality and readmission rates were highest among patients on dialysis (Figure). After adjustment, 1-year post-stroke mortality remained highest among patients on dialysis (HR 2.19, 95%CI 2.08-2.31), even after excluding in-hospital mortality and discharge to hospice (HR 2.65, 95%CI 2.49-2.81). For those discharged alive, 30-day and 1-year rehospitalization rates were also highest among patients on dialysis (HR 2.10, 95%CI 1.95-2.26; HR 2.55, 95%CI 2.44-2.66, respectively) as was the 30-day and 1-year composite of mortality and rehospitalization (HR 2.04, 95%CI 1.90-2.18; HR 2.46, 95% CI 2.36-2.56, respectively). Conclusion: Among Medicare beneficiaries with acute ischemic stroke, poststroke mortality and rehospitalization varied by CKD stage and were highest among those with advanced CKD.

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Intakes of fruits, vegetables and carbohydrate and the risk of CVD

Public Health Nutrition ◽

10.1017/s1368980008002036 ◽

2009 ◽

Vol 12 (1) ◽

pp. 115-121 ◽

Cited By ~ 29

Author(s):

Kaumudi J Joshipura ◽

Hsin-Chia Hung ◽

Tricia Y Li ◽

Frank B Hu ◽

Eric B Rimm ◽

...

Keyword(s):

Fruits And Vegetables ◽

Proportional Hazards ◽

Vegetable Intake ◽

Cox Proportional Hazards ◽

Carbohydrate Intake ◽

Leafy Vegetables ◽

Health Study ◽

Fruit Intake ◽

Green Leafy Vegetables ◽

Low Carbohydrate

AbstractBackgroundLow-carbohydrate diets could lead to reduced fruit and vegetable intake, which may be protective against CVD. The role of carbohydrate intake in modifying the association between fruits and vegetables and CVD has not been evaluated.ObjectiveTo evaluate whether carbohydrate intake affects the association between fruits and vegetables and CVD.DesignWe included participants from two large prospective studies, the Nurses’ Health Study (NHS) and the Health Professionals’ Follow-Up Study (HPFS). We followed 70 870 eligible NHS females for 16 years and 38 918 eligible HPFS males for 14 years. Diet was assessed from an FFQ updated every 4 years. Our primary outcome was ischaemic CVD (fatal and non-fatal myocardial infarction and ischaemic stroke). We used Cox proportional hazards models to evaluate the relationship between fruits and vegetables and ischaemic CVD within groups with low, moderate or high carbohydrate intake.ResultsFruit intake was strongly related with carbohydrate intake, but vegetables showed a very small correlation. Vegetable intake showed stronger associations with ischaemic CVD among the low carbohydrate group (multivariate risk ratio (RR) = 0·82 for an increment of 3 servings/d; 95 % CI 0·68, 0·99); green leafy vegetables and carotene-rich fruits and vegetables followed a similar pattern. Total fruit intake was associated with a lower risk of ischaemic CVD only among participants with moderate carbohydrate intake (RR = 0·81 comparing extreme quintiles; 95 % CI 0·70, 0·94).ConclusionsTotal vegetables, green leafy vegetables and carotene-rich fruits and vegetables showed stronger associations with ischaemic CVD among the low carbohydrate group. No consistent trends were observed for fruit intake.

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Differences in Cause-Specific Mortality Between Frail Men and Women in the United States

Innovation in Aging ◽

10.1093/geroni/igaa057.868 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 271-271

Author(s):

Matthew Lohman ◽

Amanda Sonnega ◽

Amanda Leggett ◽

Nicholas Resciniti

Keyword(s):

Older Adults ◽

Heart Disease ◽

Causes Of Death ◽

Proportional Hazards ◽

Significant Risk ◽

The United States ◽

Cox Proportional Hazards ◽

Frail Older Adults ◽

Risk Of Death ◽

Specific Mortality

Abstract While frailty is associated with risk of numerous adverse health outcomes including mortality, little is known about the most common specific causes of death among frail older adults or how these causes might differ by gender. This information may be important to understanding the frailty syndrome and to informing screening and treatment. We used linked data from the Health and Retirement Study (2004 – 2012) and the National Death Index (NDI). We analyzed data from HRS participants age 65 and older who completed a general health interview and physiological measures (n=10,490). Frailty was operationalized using the phenotype criteria – low weight, low energy expenditure, exhaustion, slow gait, and weakness. Causes of death were determined using International Classification of Diseases (v10) codes from death certificates. We used Cox proportional hazards to compare incidence of cause-specific mortality by frailty status and gender. The attributable risk of mortality due to frailty in the sample was 16.6% among women and 17.3% among men. Overall, frail older adults had greater risk of death from heart disease (hazard ratio (HR): 2.97; 95% CI: 2.18, 4.04), cancer (HR: 2.81; 95% CI: 2.01, 3.93), and dementia 2.86 (95% CI: 1.46, 5.58) but not cerebrovascular disease or accidents. Frail women were more approximately 29% more likely to die from heart disease than frail men. Findings suggest that frailty is a significant risk factor for mortality from several different causes, especially among women. Findings may help inform screening and treatment decisions for older adults at risk for frailty.

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Abstract TP201: Diabetes and the Risk of Death and Stroke Recurrence Following Ischemic Stroke

Stroke ◽

10.1161/str.47.suppl_1.tp201 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Erin L MacDougal ◽

Jeffrey J Wing ◽

William H Herman ◽

Lewis B Morgenstern ◽

Lynda D Lisabeth

Keyword(s):

Ischemic Stroke ◽

Mexican Americans ◽

Proportional Hazards ◽

Recurrence Risk ◽

Effect Modification ◽

Cox Proportional Hazards ◽

Stroke Recurrence ◽

Risk Of Death ◽

Established Risk Factor ◽

Cox Proportional Hazards Models

Background and Purpose: Diabetes mellitus (DM) is a well-established risk factor for ischemic stroke (IS), but the literature is inconsistent on the effect of DM on outcomes after IS. We sought to determine if DM increases the risk of mortality and recurrence after IS, and if these associations are greater in Mexican Americans (MA) than non-Hispanic whites (NHW). Methods: IS cases, all-cause mortality, and recurrent strokes were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project (2006-2012). Sociodemographics and clinical data were obtained from medical records and interviews. Cumulative mortality and stroke recurrence risk were estimated at 30 days and 1 year using Kaplan-Meier analysis and Cox proportional hazards models. Effect modification by ethnicity was examined. Results: There were 1,301 IS cases, 46% with a history of DM, median age 70 (IQR: 58-81), and 61% MA. Patients with DM were younger and more likely to be MA compared to patients without DM. Risk of 30-day and 1-year mortality was 8.4% and 20.5% for those with DM and 9.5% and 20.8% for those without DM, respectively. Risk of 30-day and 1-year stroke recurrence was 1.2% and 7.5% for those with DM and 1.5% and 5.8% for those without DM, respectively. Unadjusted, DM was not a significant predictor of mortality or recurrence (see table). After adjustment, DM predicted mortality (30-day HR=1.58, 95% CI: 0.98-2.53; 1-year HR=1.48, 95% CI: 1.10-2.00) but not stroke recurrence (1-year HR=1.28, 95% CI: 0.78-2.08). Effect modification by ethnicity was not significant (p>0.2 for all models). Conclusions: Given that patients with DM were significantly younger than patients without DM, the crude association between DM and mortality revealed no difference. However, after accounting for age and other factors, patients with DM were 50% more likely to die at 1 year after IS compared to patients without DM.

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Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKD

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.08310520 ◽

2020 ◽

Vol 15 (12) ◽

pp. 1728-1739

Author(s):

Flory T. Muanda ◽

Matthew A. Weir ◽

Lavanya Bathini ◽

Kristin K. Clemens ◽

Vlado Perkovic ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Older Adults ◽

Congestive Heart Failure ◽

Confidence Interval ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Risk Of Death

Background and objectivesSitagliptin, a dipeptidyl peptidase-4 inhibitor, is commonly prescribed to patients with type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses. We compare the 1-year risk of death or hospitalization with congestive heart failure in patients with CKD newly prescribed sitagliptin at >50 versus ≤50 mg/d.Design, setting, participants, & measurementsThis population-based cohort study included older adults (>66 years) with type 2 diabetes and an eGFR<45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95% confidence intervals were obtained using bootstrap variance estimators.ResultsOf 9215 patients, 6518 started sitagliptin at >50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at >50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, −0.12%; 95% confidence interval, −0.19 to −0.06) and a lower risk of all-cause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98).ConclusionsThe risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at >50 versus ≤50 mg/d.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_25_CJN08310520_final.mp3

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Abstract 11900: Influence of Competing Risks on the Association Between Warfarin and Ischemic Stroke in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study

Circulation ◽

10.1161/circ.132.suppl_3.11900 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Jeffrey M Ashburner ◽

Alan S Go ◽

Yuchiao Chang ◽

Margaret C Fang ◽

Lisa Fredman ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Competing Risks ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Subdistribution Hazard ◽

Risk Of Death

Introduction: Studies examining the association between warfarin therapy and incidence of ischemic stroke in adults with atrial fibrillation (AF) have not accounted for patients who die of non-stroke causes. Hypothesis: Accounting for the competing risk of death may provide greater understanding of the “real world” impact of warfarin on stroke risk during multiyear follow-up in a large, diverse cohort of AF patients. Methods: We assessed this association in the ATRIA community-based cohort of AF patients (n=13,559; study years 1996-2003), with thromboembolic (>90% ischemic stroke) events (TEE) being clinician-adjudicated. Extended Cox proportional hazards regression with time-varying warfarin exposure estimated the cause-specific hazard ratio (HR) for TEE while adjusting for stroke risk factors. Fine and Gray subdistribution regression was used to estimate this association while also accounting for competing death events. Results: Patients using warfarin were younger, more likely to have had a prior stroke, and to have known diabetes, coronary disease, and heart failure, and also had higher mean CHA2DS2VASc scores (3.68 vs. 3.22). The death rate was much higher in the non-warfarin group (8.1 deaths/100 person-years; 2637 deaths vs. 5.5 deaths/100 person-years; 1777 deaths on warfarin). The cause-specific HR indicated a large reduction in TE with warfarin use (adjusted HR: 0.57, 95% CI: 0.50-0.65). In subdistribution hazard models accounting for competing death events over the full follow-up of 6 years, this association was substantially attenuated (adjusted HR: 0.87, 95% CI: 0.77-0.99). In analyses limited to 1-year follow-up with only 648 competing death events, the results without accounting for competing risks (adjusted cause-specific HR: 0.55, 95% CI: 0.43-0.71) were similar to the results that did account for competing risks (adjusted subdistribution HR: 0.59, 95% CI: 0.46-0.75). Conclusions: By accounting for competing death events, our results reflect a more realistic estimate of the multi-year stroke prevention benefits of warfarin for patients with AF. Many old/frail individuals with AF will not live long enough to gain substantial benefit from warfarin.

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Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death

Neurology ◽

10.1212/wnl.0000000000011633 ◽

2021 ◽

Vol 96 (12) ◽

pp. e1655-e1662

Author(s):

Anjali Bhatla ◽

Yuliya Borovskiy ◽

Ronit Katz ◽

Matthew C. Hyman ◽

Parin J. Patel ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Inception Cohort ◽

Stroke Event ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Multivariable Adjustment

ObjectiveTo evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS).MethodsWe used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death.ResultsWe identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9–6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22–2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment.ConclusionsThe AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies.

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Hemoglobin, Albumin, Lymphocyte, and Platelet Score is Associated With Adverse Clinical Outcomes of Acute Ischemic Stroke: A Prospective Cohort Study

10.21203/rs.3.rs-38304/v1 ◽

2020 ◽

Author(s):

Mengke Tian ◽

Youfeng Li ◽

Xiao Wang ◽

Xuan Tian ◽

Lu-lu Pei ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Recurrence ◽

Vascular Events ◽

Risk Of Death ◽

Clinical Events ◽

Secondary Outcomes

Abstract Background The combined index of hemoglobin, albumin, lymphocyte and platelet (HALP) is considered as a novel score to reflect systemic inflammation and nutritional status. This study aimed to investigate the association between HALP score and adverse clinical events in patients with acute ischemic stroke (AIS). Methods This study prospectively included patients with AIS within 24 hours of admission to the First Affiliated Hospital of Zhengzhou University. The primary outcomes were all-cause death within 90 days and 1 year. The secondary outcomes included stroke recurrence and combined vascular events. The association between HALP score and adverse clinical outcomes was analyzed using Cox proportional hazards. Results A total of 1337 patients were included. Patients in the highest tertile of HALP score had a lower risk of death within 90 days and 1 year (Hazard ratio: 0.20 and 0.30; 95% confidence intervals: 0.06–0.66 and 0.13–0.69, P for trend < 0.01 for all) compared with the lowest tertile after adjusting relevant confounding factors. Similar results were found for secondary outcomes. Subgroup analyses further confirmed these association. Adding HALP score to the conventional risk factors improved prediction of death in patients with AIS within 90 days and 1 year (net reclassification index, 38.63% and 38.68%; integrated discrimination improvement, 2.43% and 2.57%; P < 0.02 for all). Conclusions High HALP score levels were associated with decreased risk of adverse clinical outcomes within 90 days and 1 year after stroke onset, suggesting that HALP score may serve as a powerful indicator for AIS.

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Jejunoileal Neuroendocrine Tumors Complicated by Intestinal Ischemic Necrosis Are Associated With Worse Overall Survival

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2015-0105-oa ◽

2016 ◽

Vol 140 (5) ◽

pp. 461-466 ◽

Cited By ~ 3

Author(s):

Michael Landau ◽

Stephen Wisniewski ◽

Jon Davison

Keyword(s):

Overall Survival ◽

Confidence Interval ◽

Neuroendocrine Tumors ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Advanced Stage ◽

Ischemic Necrosis ◽

Risk Of Death ◽

Pathologic Features ◽

Increased Risk

Context.—Jejunoileal neuroendocrine tumors (JINETs) are slow-growing, malignant tumors that are often associated with protracted survival, despite their frequent presentation at an advanced stage. A subset of JINETs is complicated by intestinal ischemic necrosis (IIN), which leads to their initial clinical presentation. Objective.—To assess the effect of IIN on overall survival in patients with JINETs. Design.—Ten JINETs with IIN during a 14-year period and a control group of 52 JINETs without IIN were identified retrospectively. The hematoxylin-eosin slides and gross descriptions were reviewed, and pathologic features were assessed. Overall survival was compared between the 2 groups using the Kaplan Meier method and Cox proportional hazards model. Results.—At 1 year postresection, only 40% (4 of 10) of the patients with IIN were alive, whereas 94% (49 of 52) of those without IIN were alive (P < .001). Patients with IIN were significantly older than those without IIN (median, 83 years versus 65.5 years, P = .001). By univariate Cox proportional hazards regression, IIN was associated with a 4.30-fold increased risk of death (95% confidence interval 1.75–10.56; P = .001). When controlling for age, advanced stage (stage III or IV), tumor grade, and synchronous carcinoma in a multivariate analysis, IIN showed a trend toward prognostic significance (2.31-fold increased risk of death; 95% confidence interval, 0.85–6.27; P = .10). Conclusions.—The pathologic identification of tumor-associated IIN portends a worse overall survival among patients with JINETs.

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