5-Azacytidine to Treat Acute Myeloid Leukemia In Elderly or Frail Patients: A Phase II Study (SAKK 30/07).

Background: Acute Myeloid Leukemia (AML) in the elderly is notoriously difficult to treat and has a low remission rate with very few long term survivors when using standard treatment approaches. Azacytidine, a hypomethylating agent, has been shown to induce remission and prolong survival in patients with myelodysplastic syndromes; studying this approach to patients with AML is therefore warranted. We present results of an ongoing phase II trial treating elderly or frail AML patients with Azacytidine. Methods: AML elderly or frail patients, and therefore unfit for an intensive chemotherapy regimens, with a WHO performance status 3 were considered for this trial. Trial therapy consisted of 100mg/m2 of Azacytidine injected subcutaneously on 5 consecutive days every 28 days up to 6 cycles, stopping at 6 months if no hematological improvement achieved, or earlier in the case of progression or complications. Treatment was continued beyond 6 months in responding patients. Trial therapy was considered uninteresting if the response rate (CR + PR) within 6 months of therapy initiation was 15% or less and promising if 34% or more. Using the exact single-stage phase II design by A'Hern with a 5% significance level and 90% power, 43 patients were required: If 10 or fewer achieved a response within 6 months the trial therapy should not be considered for further investigation in its current format for this indication and patient population. Results: Between September 2008 and January 2010, 45 evaluable patients across 10 Swiss centers were accrued with a median follow-up of 7 months (range: 0 - 13). 27 (60%) were male, median age was 74 (range: 55 - 86) years and 35 (78.8%) had performance status 0-1. Patients had been excluded from more intensive chemotherapy regimens because of age (n = 37) or due to comorbidities or patient refusal (n=8). Five patients had therapy related AML. Patients received a median of 3 (range: 1 - 10) cycles. Treatment was stopped for not achieving a response by the 6th cycle in 2 patients and earlier in 26 patients (for disease progression in 5, toxicity in 3, patient refusal in 2, recurrent infections in 1, and death in 8). Seventeen patients remain on therapy. The median time spent in the hospital was 12 days (1 - 30) in 24/38 patients hospitalized during the first treatment cycle and 13 days (2 - 28) in 15/31 patients hospitalized during subsequent cycles. Adverse events of grade III or higher most frequently reported were constitutional or hematologic, i.e. fatigue in 5, febrile neutropenia in 8, infections in 6, dyspnea in 6, anemia in 3, neutropenia in 12 and thrombocytopenia in 10, hemorrhage in 2 and retinal detachment in 5. Based on available data on 38 patients, CR/CRi or hematologic improvement or stable disease within 6 months of trial registration was observed in a proportion of patients. Final and mature data, determining whether the predefined proportion of responding patients has been reached or not, will be presented at the conference. Up to now there were a total of 26 deaths. Median overall survival time was 5.7 months (95% CI: 3.1, 8.7). Conclusions: The current results of this slightly modified Azacytidine schedule demonstrate a feasible new therapy option for elderly or frail AML patients in an outpatient setting with moderate, mainly hematologic toxicity.

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

BACKGROUND: Women with diabetes mellitus have an increased risk of cardiovascular disease (CVD) mortality and current treatment guidelines consider diabetes to be equivalent to existing CVD, but few data exist about the relative importance of these risk factors for total and cause-specific mortality in older women. METHODS: We studied 9704 women aged ≥65 years enrolled in a prospective cohort study (Study of Osteoporotic Fractures) during a mean follow-up of 13 years and compared all-cause, CVD and coronary heart disease (CHD) mortality among non-diabetic women without and with a prior history of CVD at baseline and diabetic women without and with a prior history of CVD. Diabetes mellitus and prior CVD (history of angina, myocardial infarction or stroke) were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available (>95% deaths confirmed). Ascertainment of vital status was 99% complete. Log-rank tests for the rates of death and multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. Results are reported as adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: At baseline mean age was 71.7±5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. The incidence of CVD death per 1000 person-years was 9.9 and 21.6 among non-diabetic women without and with CVD, respectively, and 23.8 and 33.3 among diabetic women without and with CVD, respectively. Compared to nondiabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR=1.82, CI: 1.60-2.07, P<0.001) and diabetic women without prior CVD (HR=2.24, CI: 1.87-2.69, P<0.001). CVD mortality was highest among diabetic women with CVD (HR=3.41, CI: 2.61-4.45, P<0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P<0.001 and P<0.05 respectively). CHD mortality did not differ significantly between non-diabetic women with CVD and diabetic women without prior CVD. CONCLUSION: Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality and a similar risk of CHD mortality compared to non-diabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD.

Implantació d'un sistema de gestió integrada: ISO 9001:00, ISO 14001:04 i OHSAS 18001:07, en un centre d'estètica i perruqueria

En aquests últims anys, són moltes les empreses que han optat per la utilització de sistemes de gestió normalitzats, per a garantir la rendibilitat i fiabilitat dels resultats de la implantació del sistema de gestió en qüestió. A la dècada dels 90 va ser quan la implantació de sistemes de gestió va començar a ser important en la majoria de sectors econòmics. L’evolució en els sistemes de gestió a trets generals va iniciar-se primerament en l’àmbit de la qualitat, seguidament en la gestió ambiental i en última instància en la prevenció de riscos laborals. Aquests tres tipus de sistemes de gestió, en els últims anys s’han anat integrant, de manera que s’han reduït els recursos i els esforços emprats en la gestió, millorant significativament l’eficàcia i l’eficiència d’aquests sistemes. L’objectiu principal que persegueix aquest projecte, és definir un sistema de gestió que permeti a l’empresa conduir les seves activitats de forma simplificada i ordenada, i que alhora faciliti la informació necessària per a corregir i millorar les activitats. Un altre objectiu que pretén aconseguir aquest projecte, és el de dissenyar un SGI que aprofiti les sinèrgies generades en els diferents àmbits de la pròpia empresa i fomenti les interaccions entre els diferents nivells de l’organització. En conseqüència, millorarà de forma important els fluxos d’informació dins de l’empresa minimitzant els esforços i la pèrdua d’informació. El mètode escollit per a la implantació del SGI, ha estat la Gestió per Processos, la qual es basa en la definició i seguiment dels processos de l’empresa, partint de les necessitats del client i acabant quan aquestes estan satisfetes. En conclusió, a la finalització del present projecte s’obtindrà un SGI, amb tots els processos de l’empresa definits i implantats, que doni compliment a les normes UNEEN-ISO 9001:00, UNE-EN-ISO 14001:04 i OHSAS 18001:07. Aquest SGI, que s’ha realitzat des d’un punt de vista documental i teòric, suposarà una millora de l’eficàcia operativa dels processos i una important millora competitiva de l’empresa.

Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.

PURPOSE: Recently, a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N(-)) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment. EXPERIMENTAL DESIGN: Gene expression profiling of frozen samples from 198 N(-) systemically untreated patients was done at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were done with the genomic risk and adjusted for the clinical risk, defined by Adjuvant! Online. RESULTS: The actual 5- and 10-year time to distant metastasis were 98% (88-100%) and 94% (83-98%), respectively, for the good profile group and 76% (68-82%) and 73% (65-79%), respectively, for the poor profile group. The actual 5- and 10-year overall survival were 98% (88-100%) and 87% (73-94%), respectively, for the good profile group and 84% (77-89%) and 72% (63-78%), respectively, for the poor profile group. We observed a strong time dependence of this signature, leading to an adjusted hazard ratio of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for time to distant metastasis and overall survival, respectively. CONCLUSION: This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.

Adenoid Cystic Carcinoma of the Breast: A Rare Cancer Network Study

Purpose/Objective(s): Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer variant. It accounts for less than 0.1% of all invasive breast malignancies. Typically, it presents as a small breast lump with a low propensity to metastasize to regional lymph nodes or distant sites. The aim of this retrospective multicenter Rare Cancer Network study is to assess prognostic factors and patterns of failure in ACC, as well as the role of radiation therapy (RT) in this rare disease. Materials/Methods: Between January 1980 and December 2007, 61 women with breast ACC were included in this study. Median age was 59 years (range, 28-94 years). The majority of the patients had good performance status (49 patients with WHO 0, 12 patients with WHO 1), and 70% of the patients (n = 42) were premenopausal. Surgery consisted of tumorectomy in 35 patients, mastectomy in 20, or quadrantectomy in 6. Median tumor size was 20 mm (range, 6-170 mm). Surgical margins were clear in 50 (82%) patients. Axillary dissection (n = 41) or sentinel node assessment (n = 10) was realized in the majority of the patients. There were 53 (87%) pN0 and 8 pNx (13%) patients. Estrogen (ER) and progesterone receptor (PR) was negative in 43 (71%) and 42 (69%) patients, respectively. In 16 patients (26%), the receptor status was unknown. Adjuvant chemotherapy or hormonotherapy was administered in 8 (13%) and 7 (12%) patients, respectively. Postoperative RT with a median total dose of 50 Gy (1.8-2.0 Gy/fraction; range, 44-70 Gy) was given in 40 patients. Results: With a median follow-up of 79 months (range, 6-285 months), 5-year overall and disease-free survival (DFS) rates were 94% (95% confidence interval [CI]: 88-100%) and 82% (95% CI: 71-93%), respectively. Five-year locoregional control rate was 95% (95% CI: 89-100%). There were only 4 patients with local relapse who were all salvaged successfully, and 4 other patients developed distant metastases. According to the Common Terminology Criteria for Adverse Events v3.0, late toxicity consisted of grade 2-3 cutaneous fibrosis in 4 (10%) patients, grade 1-2 edema in 2 (5%), and grade 3 lung fibrosis in 2 (5%). In univariate analyses, the outcome was influenced neither by the type of surgery nor the use of postoperative RT. However, positive receptor status had a negative influence on the outcome. Multivariate analysis (Cox model) revealed that negative ER (p = 0.006) or PR (p = 0.04) status was associated with improved DFS. Conclusions: ACC of the breast is a relatively indolent disease with excellent local control and survival. The prognosis of patients with ACC is much better than that for patients with other breast cancers, especially those who are ER and PR negative. The role of postoperative RT is not clear. More aggressive treatments may be warranted for patients with positive receptor status.

Silicon nanocluster sensitization of erbium ions under low-energy optical excitation

The sensitizing action of amorphous silicon nanoclusters on erbium ions in thin silica films has been studied under low-energy (long wavelength) optical excitation. Profound differences in fast visible and infrared emission dynamics have been found with respect to the high-energy (shortwavelength) case. These findings point out to a strong dependence of the energy transfer process on the optical excitation energy. Total inhibition of energy transfer to erbium states higher than thefirst excited state (4I13/2) has been demonstrated for excitation energy below 1.82 eV (excitation wavelength longer than 680 nm). Direct excitation of erbium ions to the first excited state (4I13/2)has been confirmed to be the dominant energy transfer mechanism over the whole spectral range of optical excitation used (540 nm¿680 nm).

Hydrokolloid bei diabetischen Fussulzera: besser als herkömmliche Wundverbände

Sie betreuen einen 82-jährigen Typ-2-Diabetiker mit einer 1 cm grossen Wunde an der Grosszehe. Der Patient hat sich geschnitten, als er Hornhaut entfernte. Die Wunde vergrössert sich seither stetig und sondert Flüssigkeit ab. Die Wundumgebung ist hyperkeratotisch, aufgeweicht, leicht fibrinös und feucht. Weder ist Kontakt zum darunterliegenden Knochen vorhanden noch gibt es Infektionszeichen. Der Patient ist für eine Neuropathie und Veneninsuffizienz bekannt; die Fusspulse sind spürbar. Seine Blutzuckerwerte sind stabil, der HbA1c-Wert liegt bei 7,5%. Er möchte die Wunde selbst weiter versorgen und sich regelmässig duschen können.

Cetuximab In Combination With Docetaxel In Patients (Pts) With Metastatic Castration Resistant (Mcrpc) And Docetaxel-Refractory Prostate Cancer: Final Analysis Of The Multicenter Phase Ii Trial Sakk 08/07

There is no registered treatment (ttr) for pts with mCRPC who have progressive disease during or shortly after docetaxel (doc). EGFR overexpression increases in prostate cancer during the course of the disease. We investigated efficacy and safety of the combination of the monoclonal EGFR antibody cetuximab (cet) and doc in pts with mCRPC who are doc-refractory. Methods: Pts with mCRPC progressing during or < 90 days after at least 12 weeks of doc were included. Ttr consisted of the same doc regimen as prior to progression (35mg/m2 d1,8,15 q4w or 75mg/m2 q3w) in combination with cet (400mg/m2 d1, then 250mg/m2 weekly). Primary endpoint was progression free survival (PFS) at 12 weeks defined as absence of PSA progression or progression of metastases (mets). Secondary endpoints included toxicity, PFS at 24 weeks, PSA response, response of measureable disease and overall survival. 35 pts were needed in a Simon's two stage optimal design with a power of 90% and a significance level of 5% in order to test PFS rate at 12 weeks of £10% vs ?30%. Results: 35 evaluable pts were enrolled at 15 Swiss centers between 7/08 and 9/09. Median follow up was 14.8 months. Confirmed PFS at 12 weeks was 34% (95%CI 19-52%), PFS at 24 weeks was 20% and overall survival was 12.0 months (95%CI 7.1 -15.6). 20% (7/35) had a confirmed decline in PSA ? 50% and 31% (11/35) had a confirmed PSA decline ? 30%. Of pts with measurable disease (n=24) PR, SD and PD at week 12 was 4%, 54% and 25%, respectively (17% not evaluable). 3/9 (33%) pts with PDduring last doc ttr before inclusion reached the primary endpoint compared to 7/18 (39%) with PR or SD to last doc. 54% of evaluable pts experienced grade 3 and 6% grade 4 toxicity. Discussion: The result of the primary endpoint was promising in this first trial to test cet in combination with doc in pts with docetaxel-refractory mCRPC. Because this goal was achieved in such a highly pretreated pts population it appears that inhibition of the EGFR pathway may play a more important and persistent role in the treatment of prostate cancer than perceived so far. Further research is therefore warranted. Disclosure: R. Cathomas: - Membership on advisory board for sanofi aventis (suisse) and Merck. S. Gillessen: - Membership in advisory board for Sanofi Aventis. All other authors have declared no conflicts of interest.

Friday Facts, December 10, 2010, Vol. 82

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS: We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS: Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION: Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.

Effect of cropping systems in no-till farming on the quality of a Brazilian Oxisol

The no-till system with complex cropping sequences may improve the structural quality and carbon (C) sequestration in soils of the tropics. Thus, the objective of this study was to evaluate the effects of cropping sequences after eight years under the no-till system on the physical properties and C sequestration in an Oxisol in the municipality of Jaboticabal, Sao Paulo, Brazil. A randomized split-block design with three replications was used. The treatments were combinations of three summer cropping sequences - corn/corn (Zea mays L.) (CC), soybean/soybean (Glycine max L. Merryll) (SS), and soybean-corn (SC); and seven winter crops - corn, sunflower (Helianthus annuus L.), oilseed radish (Raphanus sativus L.), pearl millet (Pennisetum americanum (L.) Leeke), pigeon pea (Cajanus cajan (L.) Millsp), grain sorghum (Sorghum bicolor (L.) Moench), and sunn hemp (Crotalaria juncea L.). Soil samples were taken at the 0-10 cm depth after eight years of experimentation. Soil under SC and CC had higher mean weight diameter (3.63 and 3.55 mm, respectively) and geometric mean diameter (3.55 and 2.92 mm) of the aggregates compared to soil under SS (3.18 and 2.46 mm). The CC resulted in the highest soil organic C content (17.07 g kg-1), soil C stock (15.70 Mg ha-1), and rate of C sequestration (0.70 Mg ha-1 yr-1) among the summer crops. Among the winter crops, soil under pigeon pea had the highest total porosity (0.50 m³ m-3), and that under sunn hemp had the highest water stable aggregates (93.74 %). In addition, sunn hemp did not differ from grain sorghum and contained the highest soil organic C content (16.82 g kg-1) and also had the highest rate of C sequestration (0.67 Mg ha-1 yr-1). The soil resistance to penetration was the lower limit of the least limiting water range, while the upper limit was air-filled porosity for soil bulk densities higher than 1.39 kg dm-3 for all cropping sequences. Within the SC sequence, soil under corn and pigeon pea increased least limiting water range by formation of biopores because soil resistance to penetration decreased with the increase in soil bulk density.

Étude exploratoire de la stabilité à long terme des indices standard du WISC-IV

Par le biais d'une procédure Test-Retest, la stabilité à long terme des indices standard du WISC-IV français a été évaluée. L'intervalle moyen entre les deux passations est de 2,33 ans. L'échantillon comprend 96 enfants « tout venant » âgés de huit à 12 ans. Les comparaisons entre les moyennes des deux passations ne montrent pas de différence significative pour indice de compréhension verbale (ICV), indice de raisonnement perceptif (IRP), indice de mémoire de travail (IMT), indice d'aptitude générale (IAG) et QIT. Au niveau interindividuel, les coefficients de corrélations témoignent d'une bonne stabilité à long terme pour ICV, IAG et QIT (allant de 0,81 à 0,82). Une analyse des différences de performances entre les deux passations indique une stabilité intra-individuelle satisfaisante pour IMT et IAG. Seul IAG présente donc une stabilité à long terme satisfaisante au niveau inter- et intra-individuel. By a Test-Retest procedure, this study explores the long-term stability of the French WISC-IV index scores. The average Test-Retest interval was 2.33 years. The sample consisted of 96 non-clinical children aged between 8 and 12 years. Mean difference between the two testings was not statistically significant for VCI, PRI, WMI, GAI and FSIQ. Test-Retest reliability correlations between the two assessments are high for VCI, GAI and FSIQ (ranging from .81 to .82). An analysis of the performance differences between two assessments indicates intra-individual stability for WMI and GAI. In sum, only GAI demonstrates reliable long-term stability at an inter-and intra-individual level.

Extraction and concentration of vapors from fire debris for forensic purposes: evaluation of the use of Radiello Passive Air Sampler

The Radiello Passive Air Sampler is one of the latest innovations developed for the sampling of pollutants in the air by passive headspace. It has been reported that its properties allow an enhanced sensitivity, reproducibility and adsorption capacity. It therefore appears to be of interest in the extraction of potential residues of ignitable liquids present in fire debris when arson is suspected. A theoretical approach and several laboratory tests have made it possible to precisely characterize in a forensic perspective the potential of the device in extracting and concentrating the vapors of ignitable liquids found in fire debris. Despite some advantages, the Radiello device appears to be less efficient than traditional axial symmetry samplers.