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Cancer in the Norwegian HTx Population; Risk Factors, Incidence and Mortality Compared to General Population
Abstracts
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aerodynamic particle size (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF). Nebulized MIL recovered at the end of an endotracheal tube (ETT) in a mechanical ventilator circuit was quantified using HPLC. All studies were performed in triplicate. Results: Mass Spectrometry did not reveal MIL degradation products or formation of new drug compounds. Aerodynamic MMAD for nebulized MIL followed a Gaussian curve distribution. MMAD ¼ 4.22 mm with GSD ¼ 2.29 mm and FPF ¼ 0.62 þ/ 0.7. 22.9% of nebulized MIL was recovered at the end of the ETT.
cancer post-HTx. Cancer is twice as common in females and tree times more frequent in male recipients than in the general population. Cancer related deaths are twice as common as among non-HTx cancer patients. 699 Conclusions: Nebulizing MIL using a vibrating mesh nebulizer attached to a mechanical ventilator circuit is feasible, results in delivery of a consistent unaltered drug product, and generates a respirable aerosol with size properties ideal for both pulmonary and systemic drug delivery.
The Impact of Donor Renal Function on Cardiac Allograft Survival: Insights into Reno-Cardiac Interactions M.A. Brisco,1 O. Laur,2 A. Kula,2 T. Gilliland,2 D.L. Jacoby,2 S.G. Coca,2 W.H.W. Tang,3 J.M. Testani.2 1Cardiovascular Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; 2Department of Medicine, Yale University School of Medicine, New Haven, CT; 3Department of Medicine, Cleveland Clinic, Cleveland, OH.
698 Cancer in the Norwegian HTx Population; Risk Factors, Incidence and Mortality Compared to General Population E. Gude,1 B. Aagnes,2 S. Tretli,2 L. Gullestad,1 S. Arora,1 A. Fiane,3 A. Andreassen.1 1Dept. of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; 2Dept. of Research, Cancer Registry of Norway, Institue of Population-Based Research, Oslo, Norway; 3Detp. of Cardiothoracic Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway. Purpose: Cancer is a major cause of death after heart transplantation (HTx). Methods and Materials: In our national HTx center we linked our HTx database to the Norwegian Cancer Registry and examined risk factors for developing cancer post-HTx using logistic regression. Standard incidence ratios (SIR) for HTx compared to the general population were estimated. Cancer survival of HTx recipients was compared to a matched non-HTx control group, consisting of 10 cancer patients per HTx recipient. Results: Of 650 HTx recipients (1983-2009) in our non-induction center, 143 recipients developed 240 cancers (130 skin, 22 lymfoproliferative and 88 solid cancers). Risk factors for developing cancer were increasing age at HTx, male sex, immunosuppressive burden (azathioprine and cyclosporine dose and use of cytotoxic rejection treatment) and smoking-years post-HTx. Independent risk factors were older age at HTx [OR¼1.08 (1.02-1.13), po0.005], azathioprine dose [OR¼1.01 (1.01-1.02), po0.001] and smoking years post-HTx [OR¼1.14 (1.03-1.25), po0.010]. SIR analysis revealed that the cancer risk was 3.6 (3.1-4.1) for men and 2.3 (1.4-3.5) for females in the HTx group compared to the general population. Highest SIR [27.8 (23.934.0)] was for males developing skin cancer. The risk of dying of cancer was higher among HTx-cancer patients;HR 2.04 (1.36-3.06), po0.001. Conclusions: In the Norwegian cohort, increasing age, azathioprine dose and smoking-years post-HTx are independent predictors of
Purpose: Myocardial necrosis and apoptosis have been observed following experimentally induced renal dysfunction (RD). Given that adverse cardiac outcomes remain strongly associated with acute kidney injury even after RD completely normalizes, many have theorized that the adverse outcomes directly result from RD-induced myocardial injury. However, it remains unclear whether this risk is the result of the RD itself, or if RD is identifying a ‘‘sicker’’ population. As such, we hypothesized that if the adverse cardiovascular outcomes associated with RD result primarily from irreversible RD-induced myocardial injury, transplantation of a heart from a donor with RD should lead to inferior graft survival. Methods and Materials: Adult patients in the UNOS registry who underwent cardiac transplantation from 1994 through June 30, 2011 with donor creatinine and urine protein available were evaluated (n¼20,438). Results: Mean donor GFR was 90.5 ⫾ 48.4 ml/min and 22.3% of donors had RD (GFRo60 ml/min). Ejection fraction was similar between donors with (61.8% ⫾ 7.8%) and without RD (61.5% ⫾ 7.8%, p¼0.05). Both donor GFR (HR¼1.000, p¼0.19) and donor proteinuria (HR¼0.999, p¼0.96) were unrelated to graft survival. Paradoxically, after adjustment for donor and recipient characteristics, better donor GFR was actually associated with significantly worsened graft survival (HR¼1.01 per 10 ml/min higher GFR, p¼0.03). However, other donor/pre-transplant factors linked to subclinical myocardial injury such as age 4 40 (HR¼1.4, po0.001), diabetes (HR¼1.09, p¼0.04), hypertension (HR¼1.09, po0.001), smoking (HR¼1.21, po0.001), and ischemic time 4 4 hrs (HR¼1.2, po0.001) were associated with reduced graft survival. Conclusions: RD in cardiac allograft donors is not associated with reduced post-transplant graft survival. These data support the hypothesis that irreversible myocardial injury induced by RD is not primarily responsible for the strong epidemiologic association between RD and adverse cardiovascular outcomes.
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aerodynamic particle size (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF). Nebulized MIL recovered at the end of an endotracheal tube (ETT) in a mechanical ventilator circuit was quantified using HPLC. All studies were performed in triplicate. Results: Mass Spectrometry did not reveal MIL degradation products or formation of new drug compounds. Aerodynamic MMAD for nebulized MIL followed a Gaussian curve distribution. MMAD ¼ 4.22 mm with GSD ¼ 2.29 mm and FPF ¼ 0.62 þ/ 0.7. 22.9% of nebulized MIL was recovered at the end of the ETT.
cancer post-HTx. Cancer is twice as common in females and tree times more frequent in male recipients than in the general population. Cancer related deaths are twice as common as among non-HTx cancer patients. 699 Conclusions: Nebulizing MIL using a vibrating mesh nebulizer attached to a mechanical ventilator circuit is feasible, results in delivery of a consistent unaltered drug product, and generates a respirable aerosol with size properties ideal for both pulmonary and systemic drug delivery.
The Impact of Donor Renal Function on Cardiac Allograft Survival: Insights into Reno-Cardiac Interactions M.A. Brisco,1 O. Laur,2 A. Kula,2 T. Gilliland,2 D.L. Jacoby,2 S.G. Coca,2 W.H.W. Tang,3 J.M. Testani.2 1Cardiovascular Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; 2Department of Medicine, Yale University School of Medicine, New Haven, CT; 3Department of Medicine, Cleveland Clinic, Cleveland, OH.
698 Cancer in the Norwegian HTx Population; Risk Factors, Incidence and Mortality Compared to General Population E. Gude,1 B. Aagnes,2 S. Tretli,2 L. Gullestad,1 S. Arora,1 A. Fiane,3 A. Andreassen.1 1Dept. of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; 2Dept. of Research, Cancer Registry of Norway, Institue of Population-Based Research, Oslo, Norway; 3Detp. of Cardiothoracic Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway. Purpose: Cancer is a major cause of death after heart transplantation (HTx). Methods and Materials: In our national HTx center we linked our HTx database to the Norwegian Cancer Registry and examined risk factors for developing cancer post-HTx using logistic regression. Standard incidence ratios (SIR) for HTx compared to the general population were estimated. Cancer survival of HTx recipients was compared to a matched non-HTx control group, consisting of 10 cancer patients per HTx recipient. Results: Of 650 HTx recipients (1983-2009) in our non-induction center, 143 recipients developed 240 cancers (130 skin, 22 lymfoproliferative and 88 solid cancers). Risk factors for developing cancer were increasing age at HTx, male sex, immunosuppressive burden (azathioprine and cyclosporine dose and use of cytotoxic rejection treatment) and smoking-years post-HTx. Independent risk factors were older age at HTx [OR¼1.08 (1.02-1.13), po0.005], azathioprine dose [OR¼1.01 (1.01-1.02), po0.001] and smoking years post-HTx [OR¼1.14 (1.03-1.25), po0.010]. SIR analysis revealed that the cancer risk was 3.6 (3.1-4.1) for men and 2.3 (1.4-3.5) for females in the HTx group compared to the general population. Highest SIR [27.8 (23.934.0)] was for males developing skin cancer. The risk of dying of cancer was higher among HTx-cancer patients;HR 2.04 (1.36-3.06), po0.001. Conclusions: In the Norwegian cohort, increasing age, azathioprine dose and smoking-years post-HTx are independent predictors of
Purpose: Myocardial necrosis and apoptosis have been observed following experimentally induced renal dysfunction (RD). Given that adverse cardiac outcomes remain strongly associated with acute kidney injury even after RD completely normalizes, many have theorized that the adverse outcomes directly result from RD-induced myocardial injury. However, it remains unclear whether this risk is the result of the RD itself, or if RD is identifying a ‘‘sicker’’ population. As such, we hypothesized that if the adverse cardiovascular outcomes associated with RD result primarily from irreversible RD-induced myocardial injury, transplantation of a heart from a donor with RD should lead to inferior graft survival. Methods and Materials: Adult patients in the UNOS registry who underwent cardiac transplantation from 1994 through June 30, 2011 with donor creatinine and urine protein available were evaluated (n¼20,438). Results: Mean donor GFR was 90.5 ⫾ 48.4 ml/min and 22.3% of donors had RD (GFRo60 ml/min). Ejection fraction was similar between donors with (61.8% ⫾ 7.8%) and without RD (61.5% ⫾ 7.8%, p¼0.05). Both donor GFR (HR¼1.000, p¼0.19) and donor proteinuria (HR¼0.999, p¼0.96) were unrelated to graft survival. Paradoxically, after adjustment for donor and recipient characteristics, better donor GFR was actually associated with significantly worsened graft survival (HR¼1.01 per 10 ml/min higher GFR, p¼0.03). However, other donor/pre-transplant factors linked to subclinical myocardial injury such as age 4 40 (HR¼1.4, po0.001), diabetes (HR¼1.09, p¼0.04), hypertension (HR¼1.09, po0.001), smoking (HR¼1.21, po0.001), and ischemic time 4 4 hrs (HR¼1.2, po0.001) were associated with reduced graft survival. Conclusions: RD in cardiac allograft donors is not associated with reduced post-transplant graft survival. These data support the hypothesis that irreversible myocardial injury induced by RD is not primarily responsible for the strong epidemiologic association between RD and adverse cardiovascular outcomes.