Primary pineal tumors: outcome and prognostic factors-a study from the Rare Cancer Network (RCN).

PURPOSE: To better define outcome and prognostic factors in primary pineal tumors. MATERIALS AND METHODS: Thirty-five consecutive patients from seven academic centers of the Rare Cancer Network diagnosed between 1988 and 2006 were included. Median age was 36 years. Surgical resection consisted of biopsy in 12 cases and resection in 21 (2 cases with unknown resection). All patients underwent radiotherapy and 12 patients received also chemotherapy. RESULTS: Histological subtypes were pineoblastoma (PNB) in 21 patients, pineocytoma (PC) in 8 patients and pineocytoma with intermediate differentiation in 6 patients. Six patients with PNB had evidence of spinal seeding. Fifteen patients relapsed (14 PNB and 1 PC) with PNB cases at higher risk (p = 0.031). Median survival time was not reached. Median disease-free survival was 82 months (CI 50 % 28-275). In univariate analysis, age younger than 36 years was an unfavorable prognostic factor (p = 0.003). Patients with metastases at diagnosis had poorer survival (p = 0.048). Late side effects related to radiotherapy were dementia, leukoencephalopathy or memory loss in seven cases, occipital ischemia in one, and grade 3 seizures in two cases. Side effects related to chemotherapy were grade 3-4 leucopenia in five cases, grade 4 thrombocytopenia in three cases, grade 2 anemia in two cases, grade 4 pancytopenia in one case, grade 4 vomiting in one case and renal failure in one case. CONCLUSIONS: Age and dissemination at diagnosis influenced survival in our series. The prevalence of chronic toxicity suggests that new adjuvant strategies are advisable.

Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice.

BACKGROUND/AIMS: After treatment with heat-killed Propionibacterium acnes mice show dense hepatic granuloma formation. Such mice develop liver injury in an interleukin (IL)-18-dependent manner after challenge with a sublethal dose LPS. As previously shown, LPS-stimulated Kupffer cells secrete IL-18 depending on caspase-1 and Toll-like receptor (TLR)-4 but independently of its signal adaptor myeloid differentiation factor 88 (MyD88), suggesting importance of another signal adaptor TIR domain-containing adapter inducing IFN-beta (TRIF). Nalp3 inflammasome reportedly controls caspase-1 activation. Here we investigated the roles of MyD88 and TRIF in P. acnes-induced hepatic granuloma formation and LPS-induced caspase-1 activation for IL-18 release. METHODS: Mice were sequentially treated with P. acnes and LPS, and their serum IL-18 levels and liver injuries were determined by ELISA and ALT/AST measurement, respectively. Active caspase-1 in LPS-stimulated Kupffer cells was determined by Western blotting. RESULTS: Macrophage-ablated mice lacked P. acnes-induced hepatic granuloma formation and LPS-induced serum IL-18 elevation and liver injury. Myd88(-/-) Kupffer cells, but not Trif(-/-) cells, exhibited normal caspase-1 activation upon TLR4 engagement in vitro. Myd88(-/-) mice failed to develop hepatic granulomas after P. acnes treatment and liver injury induced by LPS challenge. In contrast, Trif(-/-) mice normally formed the hepatic granulomas, but could not release IL-18 or develop the liver injury. Nalp3(-/-) mice showed the same phenotypes of Trif(-/-) mice. CONCLUSIONS: Propionibacterium acnes treatment MyD88-dependently induced hepatic granuloma formation. Subsequent LPS TRIF-dependently activated caspase-1 via Nalp3 inflammasome and induced IL-18 release, eventually leading to the liver injury.

Long term outcome after mitral valve repair : a risk factor analysis

Objectif: La réparation de la valve mitrale constitue le traitement de choix pour restaurer ta fonction de celle-ci. Elle est actuellement reconnue pour garantir une bonne évolution à long terme. Dans le but de faciliter les décisions périopératoires, nous avons analysé nos patients afin de déterminer les facteurs de risque ayant affecté leur évolution. Méthodes: Nous avons étudié rétrospectivement 175 premiers patients consécutifs (âge moyen : 64 +/-10.4 ans ;113 hommes) qui ont subi une réparation primaire de la valve mitrale associée à toute autre intervention cardiaque entre 1986 et 1998. Les facteurs de risque influençant le taux de réopération et la survie à long terme ont été analysés de manière uni et multivariée. Résultats: La mortalité opératoire était de 3.4 % (6 décès, 0 -22 et jours post-opératoires). La mortalité tardive était de 9.1 % (16 décès, 3e-125e mois post-opératoires). Cinq patients ont dû être réopérés. L'analyse actuarielle selon Kaplan-Meier a montré une survie à 1 année de 96 +l-1 %, une survie à 5 ans de 88 +/- 3 % et une survie à 10 ans de 69 +/- 8 %. Après 1 année, la fraction de population sans réopération était de 99 %, elle était de 97 +/-2 % après 5 ans et de 88+/-6 % après 10 ans. L'analyse multivariée a montré qu' un stade NYHA III et IV résiduel ( p=0.001, RR 4.55, 95 % IC :1.85 -14.29), une mauvaise fraction d'éjection préopératoire(p=0.013, RR 1.09, 95 % IC 1.02 -1.18), ,une régurgitation mitrale d'origine fonctionnelle (p=0.018, RR 4.17, 95% IC 1.32-16.67) ainsi qu'une étiologie ischémique (p=0.049, RR 3.13, 95% IC 1.01-10.0) constituaient tous des prédicteurs indépendant de mortalité. Une régurgitation mitrale persistante au 7 e jour post-opératoire (p= 0.005, RR 4.55, 95 % IC :1.56 -20.0), un âge inférieur à 60 ans (p = 0.012, RR 8.7, 95 % IC 2.44 - 37.8) et l'absence d'anneau prothétique (p = 0.034, RR 4.76, 95 % IC 1.79-33.3) se sont tous révélés être des facteurs de risque indépendant de réopération. Conclusion: Les réparations mitrales sont accompagnées d'une excellente survie à long terme même si leur évolution peut être influencée négativement par de nombreux facteurs de risques periopératoires. Les risques de réopération sont plus élevés chez des patients jeunes présentant une régurgitation mitrale résiduelle et n'ayant pas bénéficié de la mise en place d'un anneau prothétique.

Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study.

We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

ESPEN endorsed recommendations: nutritional therapy in major burns.

BACKGROUND & AIMS: Nutrition therapy is a cornerstone of burn care from the early resuscitation phase until the end of rehabilitation. While several aspects of nutrition therapy are similar in major burns and other critical care conditions, the patho-physiology of burn injury with its major endocrine, inflammatory, metabolic and immune alterations requires some specific nutritional interventions. The present text developed by the French speaking societies, is updated to provide evidenced-based recommendations for clinical practice. METHODS: A group of burn specialists used the GRADE methodology (Grade of Recommendation, Assessment, Development and Evaluation) to evaluate human burn clinical trials between 1979 and 2011. The resulting recommendations, strong suggestions or suggestions were then rated by the non-burn specialized experts according to their agreement (strong, moderate or weak). RESULTS: Eight major recommendations were made. Strong recommendations were made regarding, 1) early enteral feeding, 2) the elevated protein requirements (1.5-2 g/kg in adults, 3 g/kg in children), 3) the limitation of glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion, 4) to associated trace element and vitamin substitution early on, and 5) to use non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury. Suggestion were made in absence of indirect calorimetry, to use of the Toronto equation (Schoffield in children) for energy requirement determination (risk of overfeeding), and to maintain fat administration ≤ 30% of total energy delivery. CONCLUSION: The nutritional therapy in major burns has evidence-based specificities that contribute to improve clinical outcome.

Mean platelet volume in the early phase of acute ischemic stroke is not associated with severity or functional outcome.

Background: Previous studies reported an increase of mean platelet volume (MPV) in patients with acute ischemic stroke. However, its correlation with stroke severity has not been investigated. Moreover, studies on the association of MPV with functional outcome yielded inconsistent results. Methods: We included all consecutive ischemic stroke patients admitted to CHUV (Centre Hospitalier Universitaire Vaudois) Neurology Service within 24 h after stroke onset who had MPV measured on admission. The association of MPV with stroke severity (NIHSS score at admission and at 24 h) and outcome (Rankin Scale score at 3 and 12 months) was analyzed in univariate analysis. The chi(2) test was performed to compare the frequency of minor strokes (NIHSS score </=4) and good functional outcome (Rankin Scale score </=2) across MPV quartiles. The ANOVA test was used to compare MPV between stroke subtypes according to the TOAST classification. Student's two-tailed unpaired t test was performed to compare MPV between lacunar and nonlacunar strokes. MPV was generated at admission by the Sysmex XE-2100 automated cell counter (Sysmex Corporation, Kobe, Japan) from EDTA blood samples. Results: There was no significant difference in the frequency of minor strokes (p = 0.46) and good functional outcome (p = 0.06) across MPV quartiles. MPV was not associated with stroke severity or outcome in univariate analysis. There was no significant difference in MPV between stroke subtypes according to the TOAST classification (p = 0.173) or between lacunar and nonlacunar strokes (10.50 +/- 0.91 vs. 10.40 +/- 0.81 fl, p = 0.322). Conclusions: MPV, assessed within 24 h after ischemic stroke onset, is not associated with stroke severity or functional outcome.

Communication during brief intervention, intention to change, and outcome.

OBJECTIVES: To explore the relationship between patient's intention to change regarding future alcohol consumption following brief alcohol intervention (BAI) and changes in alcohol consumption 12-months later and the communication characteristics between patient and counselor during BAI. DESIGN, SETTING AND SUBJECTS: Data from 367 patients (experimental arm) of a pragmatic randomized controlled trial were used to assess the effectiveness of BAI among hazardous drinkers attending an Emergency Department (Lausanne University Hospital, Lausanne, Switzerland). Alcohol outcome measures at baseline and 12 months follow-up included usual number of drinks per week, monthly frequency of heavy episodic drinking (5 or more standard drinks for men; 4 or more for women), and the Alcohol Use Disorders Identification Test (AUDIT) score. In addition, the communication characteristics between patient and counselor were analyzed via tape recordings using the Motivational Interviewing Skill Code (MISC) from 97 participants. Patient readiness and importance to change on a 10-point Likert scale (readiness/importance to change ruler) was asked during BAI, and patient intention to change alcohol consumption (yes/no) was asked at the last step. Differences in alcohol outcome at follow-up between the 367 patients who did or did not have an intention to change consumption at baseline were compared, as were differences between these two groups in communication characteristics for the 97 who completed tape recordings. RESULTS: Patients with an intention to decrease alcohol consumption reduced alcohol use and related problems more often, and reported higher levels of importance and readiness to change than did their counterparts. Analyses of MISC-coded data showed a significantly higher use of MI-consistent skills among those with a moderation intention, but no group differences on the 8 other counselor communication skills measures were found. Analyses of patient speech during the intervention indicated that those with an intention to change their alcohol consumption significantly more often self-explored personal ambivalence towards alcohol, expressed more intensely their ability, commitment, desire, need and reason to change their alcohol use than did those in the no decrease group. CONCLUSIONS: The intention expressed by hazardous drinkers when concluding BAI is associated with both patient change talk during BAI and drinking outcome 12 months later, but is mainly independent of counselor communication skills. This intention may be an important clinical indicator of which hazardous drinkers are most likely to improve after BAI.

Interleukin-28B polymorphisms, IP-10, viral load and age predict the outcome of therapy in genotype 1 hepatitis C virus under real-life conditions

Background and Aims: IL28B polymorphisms, interferon (IFN)-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score have been reported to predict rapid (RVR) and sustained (SVR) virological response in chronic hepatitis C (CHC), but it is not known whether these factors represent independent, clinically useful predictors. The aim of the study was to assess factors (including IL28B polymorphisms, IP-10 levels and HOMA-IR score) independently predicting response to therapy in CHC under real life conditions.Methods: Multivariate analysis of factors predicting RVR and SVR in 280 consecutive, treatment-naive CHC patients treated with pegylated IFN alpha and ribavirin in a prospective multicenter study.Results: Independent predictors of RVR were HCV RNA < 400,000 IU/ml (OR11.37; 95% CI 3.03-42.6), rs12980275 AA (vs. AG/GG) (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR = 0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age < 40 yrs (OR = 4.79; 1.50-15.34) and HCV RNA < 400,000 IU/ml (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR = 6.26; 1.98-19.74) and age < 40 yrs (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (32 of 33, 97%; OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99; p=0.009) or 3 patients (OR 7.8, 1.43-42.67; p=0.01).Conclusions: In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pretreatment prediction of SVR. HOMA-IR score is not associated with viral response.

Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment.

BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is controversial. The present study aims to explore the association between baseline BP levels and BP change and outcome in the overall stroke population and in specific subgroups with regard to the presence of arterial hypertensive disease and prior antihypertensive treatment. METHODS: All patients registered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin score more than 2. A local polynomial surface algorithm was used to assess the effect of BP values on outcome in the overall population and in predefined subgroups. RESULTS: Up to a certain point, as initial BP was increasing, optimal outcome was seen with a progressively more substantial BP decrease over the next 24-48 h. Patients without hypertensive disease and an initially low BP seemed to benefit from an increase of BP. In patients with hypertensive disease, initial BP and its subsequent changes seemed to have less influence on clinical outcome. Patients who were previously treated with antihypertensives did not tolerate initially low BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined not only by initial BP levels but also by the direction and magnitude of associated BP change over the first 24-48 h.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B.

BACKGROUND: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. METHODS: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. RESULTS: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). CONCLUSIONS: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: trauma and early psychotic mania.

OBJECTIVE: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. METHODS: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. RESULTS: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect. CONCLUSIONS: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.