Avaliação dos registros de enfermagem sobre ressuscitação cardiopulmonar baseada no modelo Utstein

Estudo transversal que avaliou a qualidade dos registros de enfermagem sobre ressuscitação cardiopulmonar. Foram revisados 42 prontuários de pacientes em uma unidade de terapia intensiva, utilizando o protocolo Utstein. Houve predomínio de homens (54,8%), idade de 21 a 70 anos (38,1%), correção de cardiopatias adquiridas (42,7%), com mais de um dispositivo pré-existente (147). Como causa imediata de parada cardiorrespiratória, predominou hipotensão (48,3%) e como ritmo inicial, bradicardia (37,5%). Apenas a hora do óbito e hora da parada foram registradas em 100% da amostra. Não foi registrado treinamento dos profissionais em Suporte Avançado de Vida. As causas da parada e ritmo inicial foram registrados em 69% e 76,2% da amostra. Compressões torácicas, obtenção de vias aéreas pérvias e desfibrilação foram registradas em menos de 16%. Os registros foram considerados de baixa qualidade, podendo incorrer em sanções legais aos profissionais e não permitindo a comparação da efetividade das manobras com outros centros.

Sindrome di Down e fattori di rischio nel declino neurocognitivo

Down syndrome (DS) or Trisomy 21, occurring in 1/700 and 1/1000 livebirths, is the most common genetic disorder, characterized by a third copy of the human chromosome 21 (Hsa21). DS is associated with various defects, including congenital heart diseases, craniofacial abnormalities, immune system dysfunction, mental retardation (MR), learning and memory deficiency. The phenotypic features in DS are a direct consequence of overexpression of genes located within the triplicated region on Hsa21. In addition to developmental brain abnormalities and disabilities, people with DS by the age of 30-40 have a greatly increased risk of early-onset of Alzheimer’s disease (AD) and an apparent tendency toward premature aging. Many of the immunological anomalies in DS can be enclosed in the spectrum of multiple signs of early senescence. People with DS have an increased vulnerability to oxidative damage and many factors, including amyloid beta protein (Abeta), genotype ApoE4, oxidative stress, mutations in mitochondrial DNA (mtDNA), impairment of antioxidant enzymes, accelerated neuronal cell apoptosis, are related to neuronal degeneration and early aging in DS. SUBJECTS and METHODS: Since 2007 a population of 50 adolescents and adults with DS, 26 males and 24 females (sex-ratio: M/F = 1.08), has been evaluated for the presence of neurological features, biomarkers and genetic factors correlated with neuronal degeneration and premature aging. The control group was determined by the mother and the siblings of the patients. A neuropsychiatric evaluation was obtained from all patients. The levels of thyroid antibodies (antiTg and antiTPO) and of some biochemical markers of oxidative stress, including homocysteine (tHcy), uric acid, cobalamin, folate were measured. All patients, the mother and the siblings were genotyped for ApoE gene. RESULTS: 40% of patients, with a mild prevalence of females aged between 19 and 30 years, showed increased levels of antiTg and antiTPO. The levels of tHcy were normal in 52% patients and mildly increased in 40%; hyperomocysteinemia was associated with normal levels of thyroid antibodies in 75% of patients (p<0.005). The levels of uric acid were elevated in 26%. Our study showed a prevalence of severe MR in patients aged between 1-18 years and over 30 years. Only 3 patients, 2 females and one male, over 30 years of age, showed dementia. According to the literature, the rate of Down left-handers was high (25%) compared to the rest of population and the laterality was associated with increased levels of thyroid antibodies (70%). 21.5% of patients were ApoE4 positive (ApoE4+) with a mean/severe MR. CONCLUSIONS: Until now no biochemical evidence of oxidative damage and no deficiency or alteration of antioxidant function in our patients with DS were found. mtDNA sequencing could show some mutations age-related and associated with oxidative damage and neurocognitive decline in the early aging of DS. The final aim is found predictive markers of early-onset dementia and a target strategy for the prevention and the treatment of diseases caused by oxidative stress. REFERENCES: 1) Rachidi M, Lopes C: “Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways.” - Eur J Paediatr Neurol. May;12(3):168-82 (2008). 2) Lott IT, Head E: “Down syndrome and Alzheimer's disease: a link between development and aging.” - Ment Retard Dev Disabil Res Rev, 7(3):172-8 (2001). 3) Lee HC, Wei YH: “Oxidative Stress, Mitochondrial DNA Mutation, and Apoptosis in Aging.” - Exp Biol Med (Maywood), May;232(5):592-606 (2007).

Electrolyte disorders in the human ventricle. A simulation study.

Ventricular cells are immersed in a bath of electrolytes and these ions are essential for a healthy heart and a regular rhythm. Maintaining physiological concentration of them is fundamental for reducing arrhythmias and risk of sudden cardiac death, especially in haemodialysis patients and in the heart diseases treatments. Models of electrically activity of the heart based on mathematical formulation are a part of the efforts to improve the understanding and prediction of heart behaviour. Modern models incorporate the extensive and ever increasing amounts of experimental data in incorporating biophysically detailed mechanisms to allow the detailed study of molecular and subcellular mechanisms of heart disease. The goal of this project was to simulate the effects of changes in potassium and calcium concentrations in the extracellular space between experimental data and and a description incorpored into two modern biophysically detailed models (Grandi et al. Model; O’Hara Rudy Model). Moreover the task was to analyze the changes in the ventricular electrical activity, in particular by studying the modifications on the simulated electrocardiographic signal. We used the cellular information obtained by the heart models in order to build a 1D tissue description. The fibre is composed by 165 cells, it is divided in four groups to differentiate the cell types that compound human ventricular tissue. The main results are the following: Grandi et al. (GBP) model is not even able to reproduce the correct action potential profile in hyperkalemia. Data from hospitalized patients indicates that the action potential duration (APD) should be shorter than physiological state but in this model we have the opposite. From the potassium point of view the results obtained by using O’Hara model (ORD) are in agreement with experimental data for the single cell action potential in hypokalemia and hyperkalemia, most of the currents follow the data from literature. In the 1D simulations we were able to reproduce ECGs signal in most the potassium concentrations we selected for this study and we collected data that can help physician in understanding what happens in ventricular cells during electrolyte disorder. However the model fails in the conduction of the stimulus under hyperkalemic conditions. The model emphasized the ECG modifications when the K+ is slightly more than physiological value. In the calcium setting using the ORD model we found an APD shortening in hypocalcaemia and an APD lengthening in hypercalcaemia, i.e. the opposite to experimental observation. This wrong behaviour is kept in one dimensional simulations bringing a longer QT interval in the ECG under higher [Ca2+]o conditions and vice versa. In conclusion it has highlighted that the actual ventricular models present in literature, even if they are useful in the original form, they need an improvement in the sensitivity of these two important electrolytes. We suggest an use of the GBP model with modifications introduced by Carro et al. who understood that the failure of this model is related to the Shannon et al. model (a rabbit model) from which the GBP model was built. The ORD model should be modified in the Ca2+ - dependent IcaL and in the influence of the Iks in the action potential for letting it him produce a correct action potential under different calcium concentrations. In the 1D tissue maybe a heterogeneity setting of intra and extracellular conductances for the different cell types should improve a reproduction of the ECG signal.

Asymmetrisches Dimethylarginin als kardiovaskulärer Risikofaktor : Transportmechanismen und Auswirkungen einer Akkumulation

Die vorliegende Dissertation beschäftigt sich mit dem Membrantransporter-vermittelten Export von asymmetrischem Dimethyl-L-Arginin (ADMA) aus der Endothelzelle. Da ADMA-Plasmakonzentrationen mit Erkrankungen wie koronaren Herzkrankheiten, Atherosklerose, Bluthochdruck und Endotheldysfunktion in Verbindung gebracht werden, ist ein effektiver ADMA-Export aus der Zelle heraus unabdingbar. Um den Mechanismus hierfür aufzuklären, wurden die immortalisierte Endothelzelllinie EA.hy926 und weitere primäre Endothelzellen (humane Umbilikalvenenendothelzellen und Endothelzellen der großen und kleinen Herzgefäße) auf die Expression basischer Aminosäuretransporter mittels einer qRT-PCR hin untersucht. Dabei zeigte sich, dass alle getesteten Endothelzellen die Aminosäuretransporter hCAT-1, y+LAT1 und y+LAT2 exprimierten. Basierend auf ADMA-Exportdaten, die mit entsprechenden Transporter-überexprimierenden Xenopus laevis-Oozyten gewonnen wurden, wurde festgestellt, dass alle drei Membrantransporter ADMA exportieren konnten. Der physiologisch wichtige Exportweg für intrazellulär anfallendes ADMA scheint dabei der via y+L zu sein, da es sich hierbei um einen aktiven Exportmechanismus handelt, der im Gegentransport von im humanen Plasma reichlich vorhandenen neutralen Aminosäuren und Natriumionen den nach innen gerichteten Natriumgradienten ausnutzt. Die Wichtigkeit des Membrantransportes für die Kontrolle intrazellulärer ADMA-Konzentrationen wurde in vitro durch Entzug von extrazellulären Austauschsubstraten und einer daraus resultierenden Blockade der Transportfunktion gezeigt. Hierbei wurde innerhalb von zwei Stunden ein 2,5-facher Anstieg der intrazellulären ADMA-Konzentration festgestellt, die bei Präsenz von Austauschsubstrat für die Transporter nicht auftrat. Die Relevanz der y+LATs für den ADMA-Export wurde durch Herunterregulation dieser Proteine mittels siRNA sichtbar: Unter diesen Bedingungen konnte ADMA auch in Anwesenheit von Austauschsubstrat für das System y+L weniger effektiv exportiert werden. Eine wichtige Aufgabe des humanen Endothels ist die Bildung bioaktiven Stickstoffmonoxids, das unter anderem eine Vasodilatation der Gefäße bewirkt. Für diese NO-Synthese wird L-Arginin als Substrat von der endothelialen NO-Synthase benötigt. ADMA stellt einen kompetitiven Inhibitor dar, dessen erhöhtes intrazelluläres Vorkommen möglicherweise hemmend auf die NO-Synthase wirken könnte. Es konnten hier allerdings keine Auswirkungen eines um das 4-fache gestiegenen, intrazellulären ADMA-Spiegels auf die Tätigkeit der endothelialen NO-Synthase festgestellt werden. Möglicherweise bedarf es eines noch weiter zu Gunsten des ADMAs verschobenen, intrazellulären L-Arginin:ADMA-Verhältnisses, um eine Hemmung der NO-Synthase festzustellen. Dies könnte bei einem pathologischen Transporterausfall eintreten, der intrazellulär permanent höhere ADMA-Konzentrationen zur Folge hätte. Des Weiteren hätte ein Anstieg der Arginasetätigkeit und damit einhergehend ein Substratdefizit für die NO-Synthase den gleichen Effekt. Der translationale Ansatz mit humanen peripheren mononukleären Blutzellen von Patienten aus der 2. Medizinischen Klinik zeigte die Tendenz einer Korrelation zwischen dem ADMA-Exportvermögen und der Endothelfunktion und brachte zudem die Erkenntnis eines individuell äußerst variablen ADMA-Exportvermögens zutage.

Computational Modelling of Cardiac Electrophysiology: from Cell to Bedside

Heart diseases are the leading cause of death worldwide, both for men and women. However, the ionic mechanisms underlying many cardiac arrhythmias and genetic disorders are not completely understood, thus leading to a limited efficacy of the current available therapies and leaving many open questions for cardiac electrophysiologists. On the other hand, experimental data availability is still a great issue in this field: most of the experiments are performed in vitro and/or using animal models (e.g. rabbit, dog and mouse), even when the final aim is to better understand the electrical behaviour of in vivo human heart either in physiological or pathological conditions. Computational modelling constitutes a primary tool in cardiac electrophysiology: in silico simulations, based on the available experimental data, may help to understand the electrical properties of the heart and the ionic mechanisms underlying a specific phenomenon. Once validated, mathematical models can be used for making predictions and testing hypotheses, thus suggesting potential therapeutic targets. This PhD thesis aims to apply computational cardiac modelling of human single cell action potential (AP) to three clinical scenarios, in order to gain new insights into the ionic mechanisms involved in the electrophysiological changes observed in vitro and/or in vivo. The first context is blood electrolyte variations, which may occur in patients due to different pathologies and/or therapies. In particular, we focused on extracellular Ca2+ and its effect on the AP duration (APD). The second context is haemodialysis (HD) therapy: in addition to blood electrolyte variations, patients undergo a lot of other different changes during HD, e.g. heart rate, cell volume, pH, and sympatho-vagal balance. The third context is human hypertrophic cardiomyopathy (HCM), a genetic disorder characterised by an increased arrhythmic risk, and still lacking a specific pharmacological treatment.

Die Rolle der Topoisomerase 2 beta in der normalen Herzfunktion sowie in der Entstehung der Herzinsuffizienz

Die Herzinsuffizienz (HI) ist eine der häufigsten und teuersten medizinischen Indikationen in der heutigen Zeit. rnIn der vorliegenden Arbeit konnte zum ersten Mal die Topoisomerase 2b (Top2b) in Zusammenhang mit der Entstehung einer dilatativen Kardiomyopathie gebracht werden. rnIn einem speziellen Mausmodell war es möglich, die Top2b gewebsspezifisch und zeitspezifisch nur in Kardiomyozyten zu deletieren. Dies geschah mittels eines Tamoxifen-induzierten Cre-Rekombinase-Gendeletionsmodells. Phänotypisch zeigten die Top2b-deletierten Mäuse 8 Wochen nach der Tamoxifen-Gabe signifikant reduzierte kardiale Ejektionsfraktionen sowie erhöhte linksventrikuläre enddiastolische und endsystolische Volumina. Weder Schlagvolumen noch Körpergewicht waren verändert. Die natriuretischen Peptide ANP und BNP waren in den Top2b-deletierten Tieren ebenfalls signifikant erhöht. Zusätzlich zeigten sowohl elektronenmikroskopische Untersuchungen als auch klassische histologische Verfahren fibrotische Veränderungen und erhöhte Kollagenablagerungen in Top2b-deletierten Tieren. Begleitend dazu stiegen die mRNA-Expressionslevel von Col1a1, Col3a1, Tgfβ1 und Tgfβ2 in den deletierten Tieren 8 Wochen nach der Implementierung der Deletion signifikant an. rnIn einer genomweiten Hochdurchsatz-Sequenzierung waren bereits 2 Wochen nach Tamoxifen-Gabe 128 Gene mindestens 2-fach gegenüber der Kontrollgruppe differentiell exprimiert. Eine genauere Analyse der veränderten Genexpression ließ bereits 14 Tage nach Implementierung der Deletion kardiale Verschlechterungen vermuten. So waren neben dem atrialen natriuretischen Peptid ANP die beiden häufigsten Kollagenarten im Herzen, Col3a1 und Col1a1, hochreguliert. rnInteressanterweise beinhalteten die 37 herunterregulierten Gene 11 Transkriptionsfaktoren. Da der Top2b in den letzten Jahren eine immer stärker werdende Bedeutung in der Transkription zugesprochen wird, sollte mittels Chromatin-Immunpräzipitation ein direkter Zusammenhang zwischen der Top2b-Deletion und der Herunterregulierung der 11 Transkriptionsfaktoren sowie die Bindung der Top2b an Promotoren ausgewählter, differentiell-exprimierter Gene untersucht werden. Generell konnte keine vermehrte Bindung von Top2b an Promotorbereiche gezeigt werden, was aber nicht dem generellen Fehlen einer Bindung gleichkommen muss. Vielmehr gab es methodische Schwierigkeiten, weshalb die Bedeutung der Top2b in der Transkription im Rahmen der vorliegenden Arbeit nicht ausreichend geklärt werden konnte.rnEine Kardiomyozyten-spezifische Top2b-Deletion mündete 8 Wochen nach Tamoxifen-Gabe in eine dilatative Kardiomyopathie. Zum gegenwärtigen Zeitpunkt sind keine klaren Aussagen zum zugrundeliegenden Mechanismus der entstehenden Herzschädigung in Folge einer Top2b-Deletion zu treffen. Es gibt jedoch Hinweise darauf, dass der Tumorsuppressormarker p53 eine wichtige Rolle in der Entstehung der dilatativen Kardiomyopathie spielen könnte. So konnte 8 Wochen nach der Top2b-Deletion mittels Chromatin-Immunpräzipitation eine erhöhte Bindung von p53 an Promotorregionen von Col1a1, Tgfβ2 und Mmp2 detektiert werden. Die Bedeutung dieser Bindung, und ob aufgrund dessen die Entstehung der Fibrose erklärt werden könnte, ist zum jetzigen Zeitpunkt unklar.rn

Assessment of right ventricular systolic function: Comparison between cardiac magnetic resonance derived ejection fraction and pulsed-wave tissue Doppler imaging of the tricuspid annulus

Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Its practical determination by echocardiography remains challenging. We compared routine assessment of lateral tricuspid annular systolic motion velocity (TV(lat), cm/s) using pulsed-wave tissue Doppler imaging from the apical 4-chamber view with cardiac magnetic resonance (CMR) as reference method.

A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers

Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health.

Combined cardiac and lung volume reduction surgery

Coronary artery disease is prevalent in patients who have severe emphysema and who are being considered for lung volume reduction surgery (LVRS). Significant valvular heart diseases may also coexist in these patients. Few thoracic surgeons have performed LVRS in patients who have severe cardiac diseases. Conversely, few cardiac surgeons have been willing to undertake major cardiac surgery in patients who have severe emphysema. This report reviews the evidence regarding combined cardiac surgery and LVRS to determine the optimal management strategy for patients who have severe emphysema and who are suitable for LVRS, but who also have coexisting significant cardiac diseases that are operable.

Electroanatomic mapping of the endocardium. Implication for catheter ablation of ventricular tachycardia.

The electroanatomic mapping system Carto((R)) with its combination of anatomic and electrophysiologic information has substantially improved our understanding of arrhythmia mechanisms and substrates in patients with ventricular tachycardia (VT) and structural heart disease. Identification of the individual arrhythmogenic substrate and successful ablation guided by the combination of sinus rhythm voltage mapping and conventional electrophysiologic techniques like pace and activation/entrainment mapping are best described for patients with recurrent VT in remote myocardial infarction. In about 75-90% of the patients, the target VT can be ablated with acute success and the patients remain free of any VT recurrence in up to 75%. First results of electroanatomically guided ablation in patients with arrhythmogenic right ventricular dysplasia are promising. Data on ablation of VT in other structural heart diseases are very limited, since the arrhythmogenic substrate is very diffuse, e. g., in dilated cardiomyopathy, or there are only small patient numbers, e. g., for cardiac sarcoidosis or monomorphic VT after repair of congenital heart disease. In this article, the current status of electroanatomically guided endocardial mapping and ablation of VT in patients with structural heart disease is described.

Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.

A longitudinal comparison of cardiovascular disease risk factors among children and adolescents in the U.S. and Japan: Project HeartBeat!

Blood cholesterol and blood pressure development in childhood and adolescence have important impact on the future adult level of cholesterol and blood pressure, and on increased risk of cardiovascular diseases. The U.S. has higher mortality rates of coronary heart diseases than Japan. A longitudinal comparison in children of risk factor development in the two countries provides more understanding about the causes of cardiovascular disease and its prevention. Such comparisons have not been reported in the past. ^ In Project HeartBeat!, 506 non-Hispanic white, 136 black and 369 Japanese children participated in the study in the U.S. and Japan from 1991 to 1995. A synthetic cohort of ages 8 to 18 years was composed by three cohorts with starting ages at 8, 11, and 14. A multilevel regression model was used for data analysis. ^ The study revealed that the Japanese children had significantly higher slopes of mean total cholesterol (TC) and high density lipoprotein (HDL) cholesterol levels than the U.S. children after adjusting for age and sex. The mean TC level of Japanese children was not significantly different from white and black children. The mean HDL level of Japanese children was significantly higher than white and black children after adjusting for age and sex. The ratio of HDL/TC in Japanese children was significantly higher than in U.S. whites, but not significantly different from the black children. The Japanese group had significantly lower mean diastolic blood pressure phase IV (DBP4) and phase V (DBP5) than the two U.S. groups. The Japanese group also showed significantly higher slopes in systolic blood pressure, DBP5 and DBP4 during the study period than both U.S. groups. The differences were independent from height and body mass index. ^ The study provided the first longitudinal comparison of blood cholesterol and blood pressure between the U.S. and Japanese children and adolescents. It revealed the dynamic process of these factors in the three ethnic groups. ^

Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg(-/-) mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg(-/-) foetal hearts. CPCs harvested from Speg(-/-) mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg(-/-) mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg(-/-) mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases.

Adherence to adjuvant chemotherapy and post-treatment surveillance in a large community-based cohort of patients with colon cancer

The objective of this dissertation was to determine the initiation and completion rates of adjuvant chemotherapy, its toxicity and the compliance rates of post-treatment surveillance for elderly patients with colon cancer using the linked Surveillance, Epidemiology, and End Results – Medicare database.^ The first study assessed the initiation and completion rate of 5-fluorouracil-based adjuvant chemotherapy and its relationship with patient characteristics. Of the 12,265 patients diagnosed with stage III colon adenocarcinoma in 1991-2005, 64.4% received adjuvant chemotherapy within 3-months after tumor resection and 40% of them completed the treatment. Age, marital status, and comorbidity score were significant predictors for chemotherapy initiation and completion.^ The second study estimated the incidence rate of toxicity-related endpoints among stage III colon adenocarcinoma patients treated with chemotherapy in 1991-2005. Of the 12,099 patients, 63.9% underwent chemotherapy and had volume depletion disorder (3-month cumulative incidence rate [CIR]=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Cox regression analysis confirmed such association (HR=2.76; 95% CI=2.42-3.15). The risk of ischemic heart diseases was slightly associated with chemotherapy (HR=1.08), but significantly among patients aged <75 with no comorbidity (HR=1.70). ^ The third study determined the adherence rate of follow-up cares among patients diagnosed with stage I-III colon adenocarcinoma in 2000 - June 2002. We identified 7,348 patients with a median follow-up of 59 months. The adherence rate was 83.9% for office visits, 29.4% for CEA tests, and 74.3% for colonoscopy. Overall, 25.2% met the recommended post-treatment care. Younger age at diagnosis, white race, married, advanced stage, fewer comorbidities, and chemotherapy use were significantly associated with guideline adherence.^ In conclusions, not all colon cancer patients received chemotherapy. Receiving chemotherapy was associated with increased risk of developing gastrointestinal, hematological and cardiac toxicities. Patients were more likely to comply with the schedule for office visits and colonoscopy but failed in CEA tests. ^