Ethical issues in autologous stem cell transplantation (ASCT) in advanced breast cancer: A systematic literature review

BACKGROUND: An effectiveness assessment on ASCT in locally advanced and metastatic breast cancer identified serious ethical issues associated with this intervention. Our objective was to systematically review these aspects by means of a literature analysis. METHODS: We chose the reflexive Socratic approach as the review method using Hofmann's question list, conducted a comprehensive literature search in biomedical, psychological and ethics bibliographic databases and screened the resulting hits in a 2-step selection process. Relevant arguments were assembled from the included articles, and were assessed and assigned to the question list. Hofmann's questions were addressed by synthesizing these arguments. RESULTS: Of the identified 879 documents 102 included arguments related to one or more questions from Hofmann's question list. The most important ethical issues were the implementation of ASCT in clinical practice on the basis of phase-II trials in the 1990s and the publication of falsified data in the first randomized controlled trials (Bezwoda fraud), which caused significant negative effects on recruiting patients for further clinical trials and the doctor-patient relationship. Recent meta-analyses report a marginal effect in prolonging disease-free survival, accompanied by severe harms, including death. ASCT in breast cancer remains a stigmatized technology. Reported health-related-quality-of-life data are often at high risk of bias in favor of the survivors. Furthermore little attention has been paid to those patients who were dying. CONCLUSIONS: The questions were addressed in different degrees of completeness. All arguments were assignable to the questions. The central ethical dimensions of ASCT could be discussed by reviewing the published literature

Age-related differences in unruptured intracranial aneurysms:1-year outcomes

OBJECT: The aim of this study was to determine age-related differences in short-term (1-year) outcomes in patients with unruptured intracranial aneurysms (UIAs). METHODS: Four thousand fifty-nine patients prospectively enrolled in the International Study of Unruptured Intracranial Aneurysms were categorized into 3 groups by age at enrollment: 65 years old. Outcomes assessed at 1 year included aneurysm rupture rates, combined morbidity and mortality from aneurysm procedure or hemorrhage, and all-cause mortality. Periprocedural morbidity, in-hospital morbidity, and poor neurological outcome on discharge (Rankin scale score of 3 or greater) were assessed in surgically and endovascularly treated groups. Univariate and multivariate associations of each outcome with age were tested. RESULTS: The risk of aneurysmal hemorrhage did not increase significantly with age. Procedural and in-hospital morbidity and mortality increased with age in patients treated with surgery, but remained relatively constant with increasing age with endovascular treatment. Poor neurological outcome from aneurysm- or procedure-related morbidity and mortality did not differ between management groups for patients 65 years old and younger, but was significantly higher in the surgical group for patients older than 65 years: 19.0% (95% confidence interval [CI] 13.9%-24.4%), compared with 8.0% (95% CI 2.3%-13.6%) in the endovascular group and 4.2% (95% CI 2.3%-6.2%) in the observation group. All-cause mortality increased steadily with increasing age, but differed between treatment groups only in patients 65 years of age. Risk of endovascular treatment does not appear to increase with age. Risks and benefits of treatment in older patients should be carefully considered, and if treatment is deemed necessary for patients older than 65 years, endovascular treatment may be the best option

Aspirin as a Promising Agent for Decreasing Incidence of Cerebral Aneurysm Rupture

Background and Purpose-Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. Methods-Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case-control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. Results-A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3X weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18-0.87); reference group, no use of aspirin), patients in the "<once a month" group had an OR of 0.80 (95% CI, 0.31-2.05), and patients in the ">once a month to 2X/week" group had an OR of 0.87 (95% CI, 0.27-2.81; P=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11-0.67; P=0.03) compared with those who never take aspirin. Conclusions-Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed. (Stroke. 2011;42:3156-3162.

Incorporating patient-centered quality-of-life measures for outcome assessment after Chiari malformation type I decompression in a pediatric population: a pilot study.

OBJECTIVE: Optimal management of pediatric Chiari malformation type I (CM-I) is much debated, chiefly due to the lack of validated tools for outcome assessment, with very few tools incorporating patient-centered measures of health-related quality of life (HRQOL). Although posterior fossa decompression (PFD) benefits a subset of patients, prediction of its impact across patients is challenging. The primary aim of this study was to investigate the role of patient-centered HRQOL measures in the assessment and prediction of outcomes after PFD. METHODS: The authors collected HRQOL data from a cohort of 20 pediatric CM-I patients before and after PFD. The surveys included assessments of selected Patient-Reported Outcomes Measurement Information System (PROMIS) health domains and were used to generate the PROMIS preference (PROPr) score, which is a measure of HRQOL. PROMIS is a reliable standardized measure of HRQOL domains such as pain, fatigue, depression, and physical function, which are all relevant to CM-I. The authors then compared the PROPr scores with Chicago Chiari Outcome Scale (CCOS) scores derived from time-matched clinical documentation. Finally, the authors used the PROPr scores as an outcome measure to predict postsurgical HRQOL improvement at 1 year on the basis of patient demographic characteristics, comorbidities, and radiological and physical findings. The Wilcoxon signed-rank test, Mann-Whitney U-test, and Kendall\u27s correlation were used for statistical analysis. RESULTS: Aggregate analysis revealed improvement of pain severity after PFD (p = 0.007) in anatomical patterns characteristic of CM-I. Most PROMIS domain scores trended toward improvement after surgery, with anxiety and pain interference reaching statistical significance (p \u3c 0.002 and p \u3c 0.03, respectively). PROPr scores also significantly improved after PFD (p \u3c 0.008). Of the baseline patient characteristics, preexisting scoliosis was the most accurate negative predictor of HRQOL improvement after PFD (median -0.095 vs 0.106, p \u3c 0.001). A correlation with modest magnitude (Kendall\u27s tau range 0.19-0.47) was detected between the patient-centered measures and CCOS score. CONCLUSIONS: The authors observed moderate improvement of HRQOL, when measured using a modified panel of PROMIS question banks, in this pilot cohort of pediatric CM-I patients after PFD. Further investigations are necessary to validate this tool for children with CM-I and to determine whether these scores correlate with clinical and radiographic findings

Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: A pilot study

Objective-Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI. Methods and Results-Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue. Conclusion-Imaging with T2*-GE-MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture. © 2012 American Heart Association, Inc

Concurrent Venous Stenting of the Transverse and Occipito-Marginal Sinuses: An Analogy with Parallel Hemodynamic Circuits

Nonthrombotic intracranial venous occlusive disease (NIVOD) has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH) and various non-IIH headache syndromes. Endovascular stenting of stenotic, dominant transverse sinuses (TSs) may reduce trans-stenosis pressure gradients, decrease intracranial pressure, and alleviate symptoms in a subset of NIVOD patients. We present a case in which concurrent stenting of the occipito-marginal sinus obliterated the residual trans-stenosis pressure gradient across an initially stented dominant TS. We hypothesize that this observation may be explained using an electric-hydraulic analogy, and that this patient’s dominant TS and occipito-marginal sinus may be modeled as a parallel hemodynamic circuit. Neurointerventionalists should be aware of parallel hemodynamic drainage patterns and consider manometry and possibly additional stenting of stenotic, parallel venous outflow pathways if TS stenting alone fails to obliterate the trans-stenosis pressure gradient

Palynological signal of the Younger Dryas in the tropical Venezuelan Andes

The occurrence, or not, of the Younger Dryas cold reversal in the tropical Andes remains a controversial topic. This study reports a clear signal for this event in the Venezuelan Andes, employing high-resolution palynological analysis of a well-dated sediment core from Laguna de Los Anteojos, situated around 3900 m elevation, within grass páramo vegetation. The lake is surrounded by some Polylepis forests which are close to their upper distribution limit. The section of the core discussed here is 150-cm long and dated between about 14.68 and 9.35 cal kyr BP, using a polynomial age-depth model based on six AMS radiocarbon dates. Between 12.86 and 11.65 cal kyr BP, an abrupt shift occurred in the pollen assemblage, manifested by a decline of Podocarpus, Polylepis and Huperzia, combined with an increase in Poaceae and Asteraceae. The aquatic pteridophyte Isoëtes also decreased and disappeard, and the algae remains show their minimum values. Pollen assemblages from the Younger Dryas interval show maximum dissimilarity values compared with today’s pollen assemblage, and are more similar to modern analogs from superpáramo vegetation, growing at elevations 400–500 m higher. A lowering of vegetation zones of this magnitude corresponds to a temperature decline of between 2.5 and 3.8 °C. During this colder interval lake levels may have been lower, suggesting a decrease in available moisture. The vegetation shift documented in Anteojos record between 12.86 and 11.65 cal kyr BP is comparable to the El Abra Stadial in the Colombian Andes but it differs in magnitude. The Anteojos shift is better dated and coincides with the Younger Dryas chron as recorded in the Cariaco Basin sea surface temperature reconstructions and records of continental runoff, as well as in the oxygen isotope measurements from the Greenland ice cores. When compared to other proxies of quasi-immediate response to climate, the time lag for the response of vegetation to climate is found to be negligible at a centennial scale. The Polylepis pollen curve is especially noteworthy, as it reproduces the overall pollen trends and matches well with paleoclimatic reconstructions based on other proxies. Hence, Polylepis might be used as a reliable paleoclimatic indicator in lake sediments close to its uppermost distribution boundary