ABSTRACT
BACKGROUND: Trastuzumab emtansine (T-DM1) exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab in preclinical studies. This phase Ib/IIa study assessed the feasibility of T-DM1 + docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and T-DM1 + docetaxel ± pertuzumab in patients with HER2-positive locally advanced breast cancer (LABC). PATIENTS AND METHODS: Phase Ib (part 1) explored dose escalation, with T-DM1 + docetaxel administered for greater than or equal to six cycles in patients with MBC. Phase Ib (part 2) began with the maximum tolerated dose (MTD) identified in part 1. Patients with LABC were administered less than or equal to six cycles of T-DM1 + docetaxel or T-DM1 + docetaxel + pertuzumab. Phase IIa explored the MTDs identified in phase Ib. RESULTS: Administered with T-DM1 (3.6 mg/kg), the docetaxel MTD was 60 mg/m(2) in MBC. In LABC, the MTD was 100 mg/m(2) docetaxel in combination with T-DM1 (3.6 mg/kg), given with granulocyte colony-stimulating factor (G-CSF). Administered with T-DM1 (3.6 mg/kg) + pertuzumab (840 mg, cycle 1; 420 mg, subsequent cycles), the docetaxel MTD in LABC was 75 mg/m(2) with G-CSF support. Neutropenia was the most common grade 3-4 adverse event (AE; MBC, 72% and LABC, 29%). In total, 48% (12/25) of MBC patients and 47% (34/73) of LABC patients experienced AEs requiring dose modification. In MBC (median prior systemic agents = 5), the objective response rate was 80.0% (20/25; 95% confidence interval [CI] 59.3-93.2) and the median progression-free survival was 13.8 months (range, 1.6-33.5). The pathologic complete response (ypT0/is, ypN0) rate in LABC was 60.3% (44/73; 95% CI 48.1-71.5). Pharmacokinetic analyses indicated a low risk of drug-drug interaction between T-DM1 and docetaxel. CONCLUSIONS: T-DM1 combined with docetaxel ± pertuzumab appeared efficacious in MBC or LABC; however, nearly half of patients experienced AEs requiring dose reductions with these T-DM1 combinations. CLINICALTRIALSGOV IDENTIFIER: NCT00934856.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Maytansine/analogs & derivatives , Receptor, ErbB-2/genetics , Taxoids/administration & dosage , Trastuzumab/administration & dosage , Ado-Trastuzumab Emtansine , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Disease-Free Survival , Docetaxel , Female , Granulocyte Colony-Stimulating Factor/genetics , Humans , Maytansine/administration & dosage , Maytansine/adverse effects , Maytansine/pharmacokinetics , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Taxoids/adverse effects , Taxoids/pharmacokinetics , Trastuzumab/adverse effects , Trastuzumab/pharmacokineticsABSTRACT
The use of a suction laryngoscope that enables simultaneous suction and laryngoscopy was evaluated. 34 emergency medical technicians intubated the trachea of a manikin with simulated upper airway haemorrhage using the suction laryngoscope and the Macintosh laryngoscope, in random order. When using the suction laryngoscope, the number of oesophageal intubations was lower (3/34 vs 11/34; p=0.021) and the time taken to intubation was shorter (mean (SD) 50 (15) vs 58 (27) s; p=0.041). In cases of airway haemorrhage, the use of the suction laryngoscope might be beneficial.
Subject(s)
Airway Obstruction/therapy , Emergency Medical Technicians , Hemorrhage , Intubation, Intratracheal/instrumentation , Laryngoscopes , Suction/instrumentation , Airway Obstruction/etiology , Emergencies , Hemorrhage/complications , Humans , Manikins , Sample SizeABSTRACT
BACKGROUND: The role of CHAC1 (cation transport regulator-like protein 1), a recently identified component of the unfolded protein response (UPR) pathway, in gynaecological cancers has not yet been characterised. Now, this work illustrates CHAC1 mRNA expression and associated clinical outcome in breast and ovarian cancer. METHODS: The prognostic value of CHAC1 and its two transcript variants was investigated in 116 breast and 133 ovarian tissues using quantitative real-time reverse-transcriptase PCR. Subsequently, we conducted functional studies using short-interfering RNA-mediated knockdown and plasmid-mediated overexpression of CHAC1 in breast and ovarian cancer cells. RESULTS: Poorly differentiated tumours exhibited higher CHAC1 mRNA expression (breast cancer: P=0.004; ovarian cancer: P=0.024). Hormone receptor-negative breast tumours and advanced-staged ovarian cancers demonstrated elevated CHAC1 mRNA expression levels (P<0.001 and P=0.026, respectively). The multivariate survival analysis showed a prognostic value of both transcript variants in breast cancer (transcript variant 1: RR(death) 6.7 (2.4-18.9); P<0.001), RR(relapse) 6.7 (2.1-21.3); P=0.001); (transcript variant 2: RR(death) 4.9 (2.0-12.4); P<0.001), RR(relapse) 8.0 (2.4-26.8); P<0.001). Ovarian cancer patients aged younger than 62.6 years with high CHAC1 mRNA expression showed poorer relapse-free- and overall-survival (P=0.030 and P=0.012, respectively). In functional studies CHAC1 knockdown suppressed cell migration, whereas ectopic overexpression opposed these effects. CONCLUSION: High CHAC1 mRNA expression could be an independent indicator for elevated risk of cancer recurrence in breast and ovarian cancer.
Subject(s)
Breast Neoplasms/pathology , Cation Transport Proteins/genetics , Ovarian Neoplasms/pathology , RNA Splicing , RNA, Messenger/genetics , Adult , Aged , Aged, 80 and over , Base Sequence , Blotting, Western , Breast Neoplasms/genetics , Cell Line, Tumor , DNA Primers , Female , Gene Knockdown Techniques , Humans , Middle Aged , Ovarian Neoplasms/geneticsABSTRACT
BACKGROUND: ROTEM(®)/TEG(®) (rotational thromboelastometry) assays appear to be useful for the treatment of bleeding trauma patients. However, data on the prevalence and impact of abnormal ROTEM(®) assays are scarce. METHODS: This is a prospective cohort study of blunt trauma patients (Injury Severity Score ≥15 or Glasgow Coma Score ≤14) admitted to Innsbruck Medical University Hospital between July 2005 and July 2008. Standard coagulation tests, antithrombin (AT), prothrombin fragments (F1+2), thrombin-antithrombin complex (TAT), and ROTEM(®) assays were measured after admission. Data on 334 patients remained for final analysis. RESULTS: ROTEM(®) parameters correlated with standard coagulation tests (all Spearman r>0.5), and significant differences in mortality were detected for defined ROTEM(®) thresholds [FIBTEM 7 mm (21% vs 9%, P=0.006), EXTEM MCF (maximum clot firmness) 45 mm (25.4% vs 9.4%, P=0.001)]. EXTEM MCF was independently associated with early mortality [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.9-0.99] and MCF FIBTEM with need for red blood cell transfusion (OR 0.92, 95% CI 0.87-0.98). In polytrauma patients with or without head injury (n=274), the prevalence of low fibrinogen concentrations, impaired fibrin polymerization, and reduced clot firmness was 26%, 30%, and 22%, respectively, and thus higher than the prolonged international normalized ratio (14%). Hyperfibrinolysis increased fatality rates and occurred as frequently in isolated brain injury (n=60) as in polytrauma (n=274) (5%, 95% CI 1.04-13.92 vs 7.3%, 95% CI 4.52-11.05). All patients showed elevated F1+2 and TAT and low AT levels, indicating increased thrombin formation. CONCLUSIONS: Our data enlarge the body of evidence showing that ROTEM(®) assays are useful in trauma patients. Treatment concepts should focus on maintaining fibrin polymerization and treating hyperfibrinolysis.
Subject(s)
Blood Coagulation Disorders/diagnosis , Thrombelastography/methods , Wounds, Nonpenetrating/complications , Adult , Aged , Blood Coagulation Disorders/epidemiology , Blood Coagulation Disorders/therapy , Cohort Studies , Erythrocyte Transfusion , Female , Fibrinolysis , Humans , Male , Middle Aged , Platelet Count , Prevalence , Prospective Studies , Wounds, Nonpenetrating/bloodABSTRACT
BACKGROUND: We hypothesized that the PTH (1-84)/non-PTH (1-84) ratio (PTH ratio) might help to assess cardiovascular risk in hemodialysis patients. METHODS: In this prospective cohort study 70 prevalent hemodialysis patients were followed up to 4 years. The PTH ratio was determined at baseline. Primary outcomes were cardiovascular events (CVE) and all-cause mortality. Cumulative event-free survival was compared between patients with a ratio < 1 and those with a ratio > 1. The risk-association of the PTH ratio with CVE was examined using an adjusted Multiple Cox Proportional Hazards model. RESULTS: A PTH ratio > 1 was found in 34 patients (49%). During follow-up 26 patients suffered a CVE. Patients with a CVE showed a higher ratio than patients with event-free survival (p = 0.033). In patients with a ratio > 1 a significantly higher number of CVE occurred (53 vs. 22%; p = 0.013), and these patients showed a significantly shorter event-free survival (p = 0.032). In an adjusted Cox-proportional hazards model a higher PTH ratio was found to be independently associated with an elevated risk for CVE (HR = 3.2; 95% CI 1.06 - 13.63; p = 0.04). CONCLUSIONS: A higher PTH (1-84)/non-PTH (1-84) ratio is associated with an increased risk for CVE in hemodialysis patients and might therefore be useful for cardiovascular risk estimation in this population.
Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Kidney Failure, Chronic/therapy , Parathyroid Hormone/blood , Renal Dialysis , Aged , Analysis of Variance , Biomarkers/blood , Disease-Free Survival , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/mortality , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk FactorsABSTRACT
OBJECTIVES: To describe the sonographic appearance of the structures of the posterior cranial fossa in fetuses at 11 + 3 to 13 + 6 weeks of pregnancy and to determine whether abnormal findings of the brain and spine can be detected by sonography at this time. METHODS: This was a prospective study including 692 fetuses whose mothers attended Innsbruck Medical University Hospital for first-trimester sonography. In 3% (n = 21) of cases, measurement was prevented by fetal position. Of the remaining 671 cases, in 604 there was either a normal anomaly scan at 20 weeks or delivery of a healthy child and in these cases the transcerebellar diameter (TCD) and the anteroposterior diameter of the cisterna magna (CM), measured at 11 + 3 to 13 + 6 weeks, were analyzed. In 502 fetuses, the anteroposterior diameter of the fourth ventricle (4V) was also measured. In 25 fetuses, intra- and interobserver repeatability was calculated. RESULTS: We observed a linear correlation between crown-rump length (CRL) and CM (CM = 0.0536 × CRL - 1.4701; R2 = 0.688), TCD (TCD = 0.1482 × CRL - 1.2083; R2 = 0.701) and 4V (4V = 0.0181 × CRL + 0.9186; R2 = 0.118). In three patients with posterior fossa cysts, measurements significantly exceeded the reference values. One fetus with spina bifida had an obliterated CM and the posterior border of the 4V could not be visualized. CONCLUSIONS: Transabdominal sonographic assessment of the posterior fossa is feasible in the first trimester. Measurements of the 4V, the CM and the TCD performed at this time are reliable. The established reference values assist in detecting fetal anomalies. However, findings must be interpreted carefully, as some supposed malformations might be merely delayed development of brain structures.
Subject(s)
Biometry/methods , Cerebellum/diagnostic imaging , Cisterna Magna/diagnostic imaging , Cranial Fossa, Posterior/diagnostic imaging , Fourth Ventricle/diagnostic imaging , Spine/diagnostic imaging , Ultrasonography, Prenatal/methods , Abdomen , Cerebellum/embryology , Cisterna Magna/embryology , Cranial Fossa, Posterior/embryology , Crown-Rump Length , Feasibility Studies , Female , Fourth Ventricle/embryology , Gestational Age , Humans , Pregnancy , Pregnancy Trimester, First , Prospective Studies , Reference Values , Reproducibility of Results , Spine/embryologyABSTRACT
OBJECTIVE: Epidemiological observations have shown that women with pre-eclampsia are at increased risk for subsequent development of cardiovascular disease. We evaluated maternal haemodynamics in asymptomatic women many years after pre-eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome. DESIGN: Case-control study. SETTING: University-based department of obstetrics. POPULATION: Forty-eight women, 13-18 years after the affected pregnancy: 17 women with a history of HELLP syndrome, 14 women with a history of pre-eclampsia and 17 women following normal pregnancy (control group). METHODS: Echocardiographic examination was performed in all groups, recording the isovolumetric contraction time and isovolumetric relaxation time (ICT + IVRT), ejection time (ET), myocardial performance index (MPI), transmitral early to atrial filling velocity ratio (MV-E/MV-A), stroke volume (SV) and cardiac output (CO). MAIN OUTCOME MEASURES: Cardiac function. RESULTS: Women with previous HELLP syndrome showed a significantly increased MPI (0.34 versus 0.26; P = 0.008) and ICT + IVRT (442.16 versus 415.03; P = 0.01); MV-E/A, SV, ET and CO were not significantly different. Women with a history of pre-eclampsia showed a significantly increased MPI (0.36 versus 0.26; P = 0.006) and decreased ET (317.3 versus 328.93; P = 0.04); ICT + IVRT, MV-E/A, SV and CO were not significantly different. CONCLUSION: This study confirms epidemiological observations that women with pre-eclampsia are at increased risk for subsequent development of cardiovascular disease. Many years after HELLP syndrome or pre-eclampsia, asymptomatic women have an increased risk for impaired cardiac function as shown by an increased MPI.
Subject(s)
HELLP Syndrome/physiopathology , Hemodynamics/physiology , Pre-Eclampsia/physiopathology , Ventricular Dysfunction, Left/physiopathology , Adult , Case-Control Studies , Echocardiography , Female , Humans , Myocardial Contraction/physiology , Observer Variation , PregnancyABSTRACT
OBJECTIVE: The aim of this study was to find out on an unselected patient group whether crossing vessels have an influence on the width of the renal pelvis and what independent predictors of these target variables exist. METHODS: In this cross-sectional study, 1072 patients with arterially contrasted CT scans were included. The 2132 kidneys were supplied by 2736 arteries. RESULTS: On the right side, there were 293 additional and accessory arteries in 286 patients, and on the left side there were 304 in 271 patients. 154 renal pelves were more than 15 mm wide. The greatest independent factor for hydronephrosis on one side was hydronephrosis on the contralateral side (p<0.0001 each). Independent predictors for the width of the renal pelvis on the right side were the width of the renal pelvis on the left, female gender, increasing age and height; for the left side, predictors were the width of the renal pelvis on the right, concrements, parapelvic cysts and great rotation of the upper pole of the kidney to dorsal. Crossing vessels had no influence on the development of hydronephrosis. Only anterior crossing vessels on the right side are associated with widening of the renal pelvis by 1 mm, without making it possible to identify the vessel as an independent factor in multivariate regression models. CONCLUSION: The width of the renal pelvis on the contralateral side is the strongest independent predictor for hydronephrosis and the width of the renal pelvis. There is no link between crossing vessels and the width of the renal pelvis.
Subject(s)
Hydronephrosis/diagnostic imaging , Kidney/blood supply , Renal Artery/diagnostic imaging , Urinary Tract/blood supply , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Kidney/anatomy & histology , Kidney/diagnostic imaging , Male , Middle Aged , Organ Size , Reference Values , Renal Artery/anatomy & histology , Retrospective Studies , Tomography, X-Ray Computed , Urinary Tract/anatomy & histology , Young AdultABSTRACT
BACKGROUND: Intrathecal IgM synthesis is reported to be associated with a worse prognosis in adults with multiple sclerosis (MS). OBJECTIVE: To study the predictive value of intrathecal IgM synthesis for the clinical course of pediatric MS. METHODS: Seventy children with onset of MS before the age of 16 years and followed for a median period of 10.4 years (range: 0.4-22.8 years) were studied. The two subgroups with (n=44) or without (n=26) intrathecal IgM synthesis were distinguished by a new, very sensitive, evaluation of quantitative analysis in cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams). The clinical course and EDSS (Expanded Disability Status Scale) scores at five and ten years were compared with IgM frequencies between both groups with a new statistics program for CSF data. RESULTS: The cohort of children without intrathecal IgM production had higher numbers of attacks in the first two years and shorter time intervals between first and second attack, although this was not statistically significant (p=0.04, p=0.15 respectively). In addition there was also a trend for girls without intrathecal IgM synthesis to have a higher EDSS score after 10 years compared with the group with IgM synthesis. CONCLUSION: Intrathecal IgM synthesis is not associated with a more rapid progression of disability in pediatric MS. Reevaluation of data from previous reports about the negative predictive value of intrathecal IgM synthesis in adult MS with a CSF statistics tool show that the apparent contradiction is due to a methodological bias in the qualitative detection of 'oligoclonal' IgM or linear IgM index.
Subject(s)
Immunoglobulin M/biosynthesis , Multiple Sclerosis, Chronic Progressive/diagnosis , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Spinal Cord/immunology , Adolescent , Biomarkers/cerebrospinal fluid , Chi-Square Distribution , Child , Child, Preschool , Disability Evaluation , Disease Progression , Female , Follow-Up Studies , Germany , Humans , Immunoglobulin M/cerebrospinal fluid , Immunologic Factors/therapeutic use , Linear Models , Male , Multiple Sclerosis, Chronic Progressive/cerebrospinal fluid , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/immunology , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/immunology , Nephelometry and Turbidimetry , Predictive Value of Tests , Prognosis , Sensitivity and Specificity , Spinal Puncture , Time FactorsABSTRACT
BACKGROUND: The small sample volume needed and the prompt availability of results make viscoelastic methods like rotational thromboelastometry (ROTEM) attractive for monitoring coagulation in small children. However, data on reference ranges for ROTEM parameters in children are scarce. METHODS: Four hundred and seven children (ASA I and II) undergoing elective surgery were recruited for this prospective, two-centre, observational study. Subjects were grouped as follows: 0-3, 4-12, 13-24 months, 2-5, 6-10, and 11-16 yr. Study objectives were to establish age-dependent reference ranges for ROTEM assays, analyse age dependence of parameters, and compare ROTEM data with standard coagulation tests. RESULTS: Data from 359 subjects remained for final analysis. Except for extrinsically activated clot strength and lysis, parameters for ROTEM assays were significantly different among all age groups. The most striking finding was that subjects aged 0-3 months exhibited accelerated initiation (ExTEM coagulation time: median 48 s, Q1-Q3 38-65 s; P=0.001) and propagation of coagulation (α angle: median 78(o), Q1-Q3 69-84(o); P<0.001) and maximum clot firmness (median 62 mm, Q1-Q3 54-74 mm), although standard plasma coagulation test results were prolonged (prothrombin time: median 13.2 s, Q1-Q3 12.6-13.6 s; activated partial thromboplastin time: median 42 s, Q1-Q3 40-46 s). Lysis indices of <85% were observed in nearly one-third of all children without increased bleeding tendency. Platelet count and fibrinogen levels correlated significantly with clot strength, and fibrinogen levels correlated with fibrin polymerization. CONCLUSIONS: Reference ranges for ROTEM assays were determined for all paediatric age groups. These values will be helpful when monitoring paediatric patients and in studies of perioperative coagulation in children.
Subject(s)
Thrombelastography/methods , Adolescent , Aging/blood , Blood Coagulation Tests/methods , Blood Specimen Collection/methods , Child , Child, Preschool , Factor XIII/metabolism , Female , Fibrin/metabolism , Fibrinogen/metabolism , Humans , Infant , Infant, Newborn , Male , Reference Values , Reproducibility of Results , Sex CharacteristicsABSTRACT
PURPOSE: Abdominal aortic aneurysms (AAA) cause a considerable number of deaths. A ruptured AAA is associated with a mortality rate of 80%. The purpose of this study was to summarize the current evidence from published health economic models for the long-term effectiveness and cost-effectiveness of screening programs for AAA. MATERIALS AND METHODS: Medical, economic and health technology assessment (HTA) databases were systematically searched for cost-effectiveness models up to October 2007. Only models with a lifetime time horizon of evaluating AAA screening in men over 65 years were included in the review. Study data were extracted, standardized and summarized in evidence tables and cost-effectiveness plots. RESULTS: We reviewed 8 cost-effectiveness models published between 1993 and 2007 comparing AAA screening and lack of screening in men over 60. One model yielded a loss of life-years at additional costs. The remaining seven models yielded gains in life expectancy ranging from 0.02 to 0.28LYs. Gains in quality-adjusted life expectancy reported by six of the seven models ranged from 0.015 to 0.059 QALYs. Incremental costs ranged from 96 to 721 Euros. Incremental cost-effectiveness ratios (ICER) ranged from 1443 to 13 299 Euros per LY or QALY gained. CONCLUSION: Based on our analysis, the introduction of a screening program to identify AAA will probably gain additional life years and quality of life at acceptable extra costs. The target population for a screening program should be men 65 years and older.
Subject(s)
Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/economics , Diagnostic Imaging/economics , Mass Screening/economics , Age Factors , Aged , Aortic Aneurysm, Abdominal/mortality , Aortic Rupture/diagnosis , Aortic Rupture/economics , Aortic Rupture/mortality , Cost-Benefit Analysis , Germany , Humans , Male , Middle Aged , Quality-Adjusted Life Years , Risk Factors , Sex FactorsABSTRACT
INTRODUCTION: The aim of this retrospective study was to compare the outcome of thoracic endovascular aortic repair (TEVAR) to that of medical therapy in patients with acute type B aortic dissection (TBD). MATERIALS AND METHODS: From July 1996 to April 2008, 88 patients presenting with acute TBD underwent either TEVAR (group A, n=38) or medical therapy (group B, n=50). Indications for TEVAR were intractable pain, aortic branch compromise resulting in end-organ ischemia, rapid aortic dilatation and rupture. Follow-up was performed postinterventionally, at 3, 6 and 12 months and yearly thereafter and included clinical examinations and computed tomography (CT), as well as aortic diameter measurements and assessment of thrombosis. RESULTS: Mean follow-up was 33 months in group A and 36 months in group B. The overall mortality rate was 23.7% in group A and 24% in group B, where 4 patients died of late aortic rupture. In group A, complications included 9 endoleaks and 4 retrograde type A dissections, 3 patients were converted to open surgery and 2 needed secondary intervention. None of the patients developed paraplegia. In group B, 4 patients were converted to open surgery and 2 to TEVAR. The maximal aortic diameter increased in both groups. Regarding the extent of thrombosis, our analyses showed slightly better overall results after TEVAR, but they also showed a tendency towards approximation between the two groups during follow-up. CONCLUSION: TEVAR is a feasible treatment option in acute TBD. However, several serious complications may occur during and after TEVAR and it should therefore be reserved to patients with life-threatening symptoms.
Subject(s)
Aortic Aneurysm/therapy , Aortic Dissection/therapy , Blood Vessel Prosthesis , Fibrinolytic Agents/administration & dosage , Stents , Vascular Surgical Procedures/methods , Adult , Aged , Aged, 80 and over , Aortic Dissection/diagnosis , Aortic Aneurysm/diagnosis , Humans , Middle AgedABSTRACT
BACKGROUND: Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk. METHODS: Serum triglyceride concentrations were collected in a health investigation (1988-2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI). RESULTS: In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47-2.54), rectal (HR, 1.56; 95% CI, 1.00-2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00-3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin's lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found. CONCLUSIONS: Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.
Subject(s)
Neoplasms/etiology , Triglycerides/blood , Adult , Aged , Cohort Studies , Female , Genital Neoplasms, Female/etiology , Humans , Male , Middle Aged , Prostatic Neoplasms/etiology , RiskABSTRACT
BACKGROUND: The relationship between serum cholesterol and cancer incidence remains controversial. PATIENTS AND METHODS: We investigated the association of total serum cholesterol (TSC) with subsequent cancer incidence in a population-based cohort of 172 210 Austrian adults prospectively followed up for a median of 13.0 years. Cox regression, allowing for time-dependent effects, was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the association of TSC with cancer. RESULTS: We observed pronounced short-term associations of TSC and overall cancer incidence in both men and women. For malignancies diagnosed shortly (<5 months) after baseline TSC measurement, the highest TSC tertile (>235.0 mg/dl in men and >229.0 in women) compared with the lowest tertile (<194.0 mg/dl in men and <190.0 in women) was associated with a significantly lower overall cancer risk [HR = 0.58 (95% CI 0.43-0.78, P(trend) = 0.0001) in men, HR = 0.69 (95% CI 0.49-0.99, P(trend) = 0.03) in women]. However, after roughly 5 months from baseline measurement, overall cancer risk was not significantly associated with TSC. The short-term inverse association of TSC with cancer was mainly driven by malignancies of the digestive organs and lymphoid and hematopoietic tissue. CONCLUSION: The short-term decrease of cancer risk seen for high levels of TSC may largely capture preclinical effects of cancer on TSC.
Subject(s)
Cholesterol/blood , Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/blood , Prospective Studies , Young AdultABSTRACT
BACKGROUND: It has been hypothesized that serum uric acid (SUA), via its antioxidant properties may protect against carcinogenesis. However, few epidemiological investigations have addressed this association and previous findings are inconsistent. PATIENTS AND METHODS: We prospectively investigated the relation of SUA levels to subsequent cancer mortality in a large cohort of 28613 elderly Austrian women with a median follow-up of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independently related factor to fatal cancer events. RESULTS: High SUA (>5.41 mg/dL) was independently associated with increased risk of total cancer mortality (p<0.0001); the adjusted hazard ratio for the highest versus lowest quartile of SUA was 1.27 (1.08-1.48). SUA levels were further positively related to deaths from malignant neoplasms of breast and female genital organs (P = 0.02) and nervous system and unspecified sites (P = 0.02). We found no evidence for an inverse relationship between SUA levels and risk of total or site-specific cancer mortality. CONCLUSION: Our results are contrary to the proposed antioxidant and protective effect of SUA against cancer and rather suggest high SUA concentrations to be associated with outcome possibly reflecting more serious prognostic indication.
Subject(s)
Antioxidants/metabolism , Neoplasms/blood , Neoplasms/mortality , Uric Acid/blood , Age Factors , Aged , Aged, 80 and over , Austria , Biomarkers, Tumor/blood , Cohort Studies , Female , Humans , Neoplasms/prevention & control , Primary Prevention , Probability , Proportional Hazards Models , Prospective Studies , Risk Factors , Sensitivity and Specificity , Survival Analysis , Uric Acid/analysisABSTRACT
For patients with symptomatic carotid stenosis, benefit from carotid artery stenting (CAS) highly depends on the 30-day stroke and death rates. Identification of predictors of unfavourable outcome would help guide the patient selection. We analysed the influence of clinical and angiographic factors on the 30-day outcomes of 77 consecutive patients who underwent CAS for > or = 60% symptomatic carotid stenosis within 180 days of transient ischaemic attack or moderate stroke (modified Rankin Scale score < or = 3). The 30-day composite end-point for stroke (7.8%) and death of any cause (1.3%) was 9.1%. Patients with complicated CAS were older than patients with uncomplicated CAS (mean age 75.1 +/- 8.2 vs. 65.9 +/- 9.5 years, P = 0.015) and underwent stenting significantly earlier after the qualifying event: median delay 1.5 weeks (range: 0.2-3.0) vs. 3.2 weeks (range: 0.5-26), P = 0.004. In multivariate logistic regression analyses, age [odds ratio (OR) = 1.148; 95% confidence interval (CI): 1.011-1.304 and P = 0.033] and delay of treatment < 2 weeks (OR = 22.399; 95% CI: 2.245-223.445 and P = 0.008) remained the only variables significantly associated with 30-day outcome. CAS carries a considerable risk in old patients and when performed early (< 2 weeks) after the qualifying event. Future reports should address the timing of CAS.