Modulation of fructose metabolism by dietary factors

High fructose consumption is associated with obesity and characteristics of metabolic syndrome. This includes insulin resistance, dyslipidemia, type II diabetes and hepatic steatosis, the hepatic component of metabolic syndrome. Short term high fructose consumption in healthy humans is considered as a study model to increase intrahepatocellular lipids (IHCL). Protein supplementation added to a short term high fructose diet exerts a protective role on hepatic fat accumulation. Fructose disposal after an acute fructose load is well established. However, fructose disposal is usually studied when a high intake of fructose is ingested. Interaction of fructose with other macronutrients on fructose disposal is not clearly established. We wanted to assess how fructose disposal is modulated with nutritional factors. For the first study, we addressed the question of how would essential amino acid (EAA) supplemented to a high fructose diet have an impact on hepatic fat accumulation? We tried to distinguish which metabolic pathways were responsible for the increase in IHCL induced by high fructose intake and how those pathways would be modulated by EAA. After 6 days of hypercaloric high fructose diet, we observed, as expected an increase in IHCL modulated by an increase in VLDL-triglycerides and an increase in VLDL-13C-palmitate production. When adding a supplementation in EAA, we observed a decrease in IHCL but we could not define which mechanism was responsible for this process. With the second study, we were interested to observe fructose disposal after a test meal that contained lipid, protein and a physiologic dose of fructose co-ingested or not with glucose. When ingested with other macronutrients, hepatic fructose disposal is similar as when ingested as pure fructose. It induced oxidation, gluconeogenesis followed by glycogen synthesis, conversion into lactate and to a minor extent by de novo lipogenesis. When co- ingested with glucose decreased fructose oxidation as well as gluconeogenesis and an increased glycogen synthesis without affecting de novo lipogenesis or lactate. We were also able to observe induction of intestinal de novo lipogenesis with both fructose and fructose co- ingested with glucose. In summary, essential amino acids supplementation blunted increase in hepatic fat content induced by a short term chronic fructose overfeeding. However, EAA failed to improve other cardiovascular risk factors. Under isocaloric condition and in the frame of an acute test meal, physiologic dose of fructose associated with other macronutrients led to the same fructose disposal as when fructose is ingested alone. When co-ingested with glucose, we observed a decrease in fructose oxidation and gluconeogenesis as well as an increased in glycogen storage without affecting other metabolic pathways. - Une consommation élevée en fructose est associée à l'obésité et aux caractéristiques du syndrome métabolique. Ces dernières incluent une résistance à l'insuline, une dyslipidémie, un diabète de type II et la stéatose hépatique, composant hépatique du syndrome métabolique. À court terme une forte consommation en fructose chez l'homme sain est considérée comme un modèle d'étude pour augmenter la teneur en graisse hépatique. Une supplémentation en protéines ajoutée à une alimentation riche en fructose de courte durée a un effet protecteur sur l'accumulation des graisses au niveau du foie. Le métabolisme du fructose après une charge de fructose aiguë est bien établi. Toutefois, ce dernier est généralement étudié quand une consommation élevée de fructose est donnée. L'interaction du fructose avec d'autres macronutriments sur le métabolisme du fructose n'est pas connue. Nous voulions évaluer la modulation du métabolisme du fructose par des facteurs nutritionnels. Pour la première étude, nous avons abordé la question de savoir quel impact aurait une supplémentation en acides aminés essentiels (AEE) associé à une alimentation riche en fructose sur l'accumulation des graisses hépatiques. Nous avons essayé de distinguer les voies métaboliques responsables de l'augmentation des graisses hépatiques induite par l'alimentation riche en fructose et comment ces voies étaient modulées par les AEE. Après 6 jours d'une alimentation hypercalorique riche en fructose, nous avons observé, comme attendu, une augmentation des graisses hépatiques modulée par une augmentation des triglycérides-VLDL et une augmentation de la production de VLDL-13C-palmitate. Lors de la supplémentation en AEE, nous avons observé une diminution des graisses hépatiques mais les mécanismes responsables de ce processus n'ont pas pu être mis en évidence. Avec la seconde étude, nous nous sommes intéressés à observer le métabolisme du fructose après un repas test contenant des lipides, des protéines et une dose physiologique de fructose co-ingéré ou non avec du glucose. Lorsque le fructose était ingéré avec les autres macronutriments, le devenir hépatique du fructose était similaire à celui induit par du fructose pur. Il a induit une oxydation, suivie d'une néoglucogenèses, une synthèse de glycogène, une conversion en lactate et dans une moindre mesure une lipogenèse de novo. Lors de la co-ngestion avec du glucose, nous avons observé une diminution de l'oxydation du fructose et de la néoglucogenèse et une augmentation de la synthèse du glycogène, sans effet sur la lipogenèse de novo ni sur le lactate. Nous avons également pu mettre en évidence que le fructose et le fructose ingéré de façon conjointe avec du glucose ont induit une lipogenèse de novo au niveau de l'intestin. En résumé, la supplémentation en acides aminés essentiels a contrecarré l'augmentation de la teneur en graisse hépatique induite par une suralimentation en fructose sur le court terme. Cependant, la supplémentation en AEE a échoué à améliorer d'autres facteurs de risque cardiovasculaires. Dans la condition isocalorique et dans le cadre d'un repas test aiguë, la dose physiologique de fructose associée à d'autres macronutriments a conduit aux mêmes aboutissants du métabolisme du fructose que lorsque le fructose est ingéré seul. Lors de la co-ngestion avec le glucose, une diminution de l'oxydation du fructose est de la néoglucogenèse est observée en parallèle à une augmentation de la synthèse de glycogène sans affecter les autres voies métaboliques.

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

BACKGROUND: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7), 0.8 (0.4-1.6), 1.6 (0.8-3.2), 3.3 (1.7-6.6) respectively, and 2.3 (1.1-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5), 2.8 (1.7-4.5) and 7.8 (4.5-13.5), respectively, and 2.8 (1.6-4.8) for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices.

CONTEXT: Infection of implantable cardiac devices is an emerging disease with significant morbidity, mortality, and health care costs. OBJECTIVES: To describe the clinical characteristics and outcome of cardiac device infective endocarditis (CDIE) with attention to its health care association and to evaluate the association between device removal during index hospitalization and outcome. DESIGN, SETTING, AND PATIENTS: Prospective cohort study using data from the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), conducted June 2000 through August 2006 in 61 centers in 28 countries. Patients were hospitalized adults with definite endocarditis as defined by modified Duke endocarditis criteria. MAIN OUTCOME MEASURES: In-hospital and 1-year mortality. RESULTS: CDIE was diagnosed in 177 (6.4% [95% CI, 5.5%-7.4%]) of a total cohort of 2760 patients with definite infective endocarditis. The clinical profile of CDIE included advanced patient age (median, 71.2 years [interquartile range, 59.8-77.6]); causation by staphylococci (62 [35.0% {95% CI, 28.0%-42.5%}] Staphylococcus aureus and 56 [31.6% {95% CI, 24.9%-39.0%}] coagulase-negative staphylococci); and a high prevalence of health care-associated infection (81 [45.8% {95% CI, 38.3%-53.4%}]). There was coexisting valve involvement in 66 (37.3% [95% CI, 30.2%-44.9%]) patients, predominantly tricuspid valve infection (43/177 [24.3%]), with associated higher mortality. In-hospital and 1-year mortality rates were 14.7% (26/177 [95% CI, 9.8%-20.8%]) and 23.2% (41/177 [95% CI, 17.2%-30.1%]), respectively. Proportional hazards regression analysis showed a survival benefit at 1 year for device removal during the initial hospitalization (28/141 patients [19.9%] who underwent device removal during the index hospitalization had died at 1 year, vs 13/34 [38.2%] who did not undergo device removal; hazard ratio, 0.42 [95% CI, 0.22-0.82]). CONCLUSIONS: Among patients with CDIE, the rate of concomitant valve infection is high, as is mortality, particularly if there is valve involvement. Early device removal is associated with improved survival at 1 year.

Clinical characteristics, prognosis, and treatment of pelvic cryptorchid seminoma.

PURPOSE: To analyze the clinical characteristics, prognosis, and treatment outcome of pelvic cryptorchid seminoma (PCS), and to determine whether whole abdominal-pelvic irradiation for Stage I disease is necessary. METHODS AND MATERIALS: From 1958 to 1991, 60 patients with PCS were treated at the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing. They presented with a lower abdominal mass and showed a predominance for the right side. A high proportion of patients with PCS [26 of 60 (43%)] had metastatic disease, compared to 20% of those with scrotal seminoma, and there was a tendency toward a higher frequency of pelvic nodal metastases. There were 34 Stage I, 6 Stage IIA, 11 Stage IIB, 5 Stage III, and 4 Stage IV patients. Of these 60 patients, 56 underwent laparotomy with or without cryptorchiectomy (37 radical orchiectomy, 7 partial orchiectomy, and 12 biopsy of the primary or cervical node), and 4 cervical node biopsy only. All patients were further treated with radiotherapy, chemotherapy, or a combination of both. Patients with Stage I and II disease received radiotherapy, whereas patients with Stage III and IV were treated with chemotherapy. RESULTS: The overall and disease-free survivals at 5 and 10 years were 92% and 87%, and 88% and 84%, respectively. The 5- and 10-year survivals were 100% for Stage I, 94% and 87% for Stage II, and 56% and 42% for Stage III/IV, respectively (p < 0.05). Volume of irradiation, i.e., whole abdominal-pelvic radiotherapy (10 patients), versus hockey-stick encompassing paraaortic, ipsilateral iliac nodes and the primary tumor or tumor bed (17) did not influence outcome in Stage I patients. Five patients relapsed within 2-12 years after treatment, and four of these patients were successfully salvaged. Four patients developed a second malignant tumor and died. CONCLUSION: Stage I and II PCS can be adequately controlled by radiotherapy regardless of the surgical procedure. Whole abdominal-pelvic irradiation for Stage I and IIA disease is not required, and fields can be limited to the paraaortic, ipsilateral iliac nodes and primary tumor or tumor bed. We recommend platinum-based chemotherapy for Stage IIB-IV PCS.

Comparison between morphological and staining characteristics of live and dead eggs of Schistosoma mansoni

Schistosoma mansoni eggs are classified, according to morphological characteristics, as follows: viable mature and immature eggs; dead mature and immature eggs, shells and granulomas. The scope of this study was to compare the staining characteristics of different morphological types of eggs in the presence of fluorescent labels and vital dyes, aiming at differentiating live and dead eggs. The eggs were obtained from the intestines of infected mice, and put into saline 0.85%. The fluorescent labels were Hoechst 33258 and Acridine Orange + Ethidium Bromide and vital dyes (Trypan Blue 0.4% and Neutral Red 1%). When labelled with the probe Hoechst 33258, some immature eggs, morphologically considered viable, presented fluorescence (a staining characteristic detected only in dead eggs); mature eggs did not present fluorescence, and the other types of dead eggs, morphologically defined, showed fluorescence. As far as Acridine Orange + Ethidium Bromide are concerned, either the eggs considered to be live, or the dead ones, presented staining with green color, and only the hatched and motionless miracidium was stained with an orange color. Trypan Blue was not able to stain the eggs, considered to be dead but only dead miracidia which had emerged out of the shell. Neutral Red stained both live and dead eggs. Only the fluorescent Hoechst 33258 can be considered a useful tool for differentiation between dead and live eggs.

The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase

Available evidence suggests that the antischistosomal drug oxamniquine is converted to a reactive ester by a schistosome enzyme that is missing in drug-resistant parasites. This study presents data supporting the idea that the active ester is a sulfate and the activating enzyme is a sulfotransferase. Evidence comes from the fact that the parasite extract loses its activating capability upon dialysis, implying the requirement of some dialyzable cofactor. The addition of the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) restored activity of the dialyzate, a strong indication that a sulfotransferase is probably involved. Classical sulfotransferase substrates like beta-estradiol and quercetin competitively inhibited the activation of oxamniquine. Furthermore, these substrates could be sulfonated in vitro using an extract of sensitive (but not resistant) schistosomes. Gel filtration analysis showed that the activating factor eluted in a fraction corresponding to a molecular mass of about 32 kDa, which is the average size of typical sulfotransferase subunits. Ion exchange and affinity chromatography confirmed the sulfotransferase nature of the enzyme. Putative sulfotransferases present in schistosome databases are being examined for their possible role as oxamniquine activators.

Capsaicin mimics mechanical load-induced intracellular signaling events: involvement of TRPV1-mediated calcium signaling in induction of skeletal muscle hypertrophy.

Mechanical load-induced intracellular signaling events are important for subsequent skeletal muscle hypertrophy. We previously showed that load-induced activation of the cation channel TRPV1 caused an increase in intracellular calcium concentrations ([Ca ( 2+) ]i) and that this activated mammalian target of rapamycin (mTOR) and promoted muscle hypertrophy. However, the link between mechanical load-induced intracellular signaling events, and the TRPV1-mediated increases in [Ca ( 2+) ]i are not fully understood. Here we show that administration of the TRPV1 agonist, capsaicin, induces phosphorylation of mTOR, p70S6K, S6, Erk1/2 and p38 MAPK, but not Akt, AMPK or GSK3β. Furthermore, the TRPV1-induced phosphorylation patterns resembled those induced by mechanical load. Our results continue to highlight the importance of TRPV1-mediated calcium signaling in load-induced intracellular signaling pathways.

Mapping the molecular characteristics of Brazilian human T-cell lymphotropic virus type 1 Env (gp46) and Pol amino acid sequences for vaccine design

This study was carried out to evaluate the molecular pattern of all available Brazilian human T-cell lymphotropic virus type 1 Env (n = 15) and Pol (n = 43) nucleotide sequences via epitope prediction, physico-chemical analysis, and protein potential sites identification, giving support to the Brazilian AIDS vaccine program. In 12 previously described peptides of the Env sequences we found 12 epitopes, while in 4 peptides of the Pol sequences we found 4 epitopes. The total variation on the amino acid composition was 9 and 17% for human leukocyte antigen (HLA) class I and class II Env epitopes, respectively. After analyzing the Pol sequences, results revealed a total amino acid variation of 0.75% for HLA-I and HLA-II epitopes. In 5 of the 12 Env epitopes the physico-chemical analysis demonstrated that the mutations magnified the antigenicity profile. The potential protein domain analysis of Env sequences showed the loss of a CK-2 phosphorylation site caused by D197N mutation in one epitope, and a N-glycosylation site caused by S246Y and V247I mutations in another epitope. Besides, the analysis of selection pressure have found 8 positive selected sites (w = 9.59) using the codon-based substitution models and maximum-likelihood methods. These studies underscore the importance of this Env region for the virus fitness, for the host immune response and, therefore, for the development of vaccine candidates.

Success of referral for alcohol dependent patients from a general hospital: predictive value of patient and process characteristics.

To assess the effectiveness of a multidisciplinary evaluation and referral process in a prospective cohort of general hospital patients with alcohol dependence. Alcohol-dependent patients were identified in the wards of the general hospital and its primary care center. They were evaluated and then referred to treatment by a multidisciplinary team; those patients who accepted to participate in this cohort study were consecutively included and followed for 6 months. Not included patients were lost for follow-up, whereas all included patients were assessed at time of inclusion, 2 and 6 months later by a research psychologist in order to collect standardized baseline patients' characteristics, process salient features and patients outcomes (defined as treatment adherence and abstinence). Multidisciplinary evaluation and therapeutic referral was feasible and effective, with a success rate of 43%for treatment adherence and 28%for abstinence at 6 months. Among patients' characteristics, predictors of success were an age over 45, not living alone, being employed and being motivated to treatment (RAATE-A score &lt; 18), whereas successful process characteristics included detoxification of the patient at time of referral and a full multidisciplinary referral meeting. This multidisciplinary model of evaluation and referral of alcohol dependent patients of a general hospital had a satisfactory level of effectiveness. Predictors of success and failure allow to identify subsets of patients for whom new strategies of motivation and treatment referral should be designed.

The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C.

Summary.  The outcome of hepatitis C virus (HCV) infection and the likelihood of a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. In vitro studies demonstrated that bile acids (BA) interfere with antiviral interferon effects. We investigate the influence of plasma BA concentrations and an ABCB11 polymorphism associated with lower transporter expression on viral load and SVR. Four hundred and fifty-one Caucasian HCV-patients treated with PEG-interferon and ribavirin were included in the study. ABCB11 1331T>C was genotyped, and plasma BA levels were determined. The 1331C allele was slightly overrepresented in HCV-patients compared to controls. In HCV-patients, a significant difference between patients achieving SVR vs non-SVR was observed for HCV-2/3 (5 vs 9 μm; P = 0.0001), while median BA levels in HCV-1 were marginally elevated. Normal BA levels <8 μm were significantly associated with SVR (58.3%vs 36.3%; OR 2.48; P = 0.0001). This difference was significant for HCV-2/3 (90.7%vs 67.6%; P = 0.002) but marginal in HCV-1 (38.7%vs 27.8%; P = 0.058). SVR rates were equivalent between ABCB11 genotypes for HCV-1, but increased for HCV-2/3 (TT 100%vs CC 78%; OR 2.01; P = 0.043). IL28B genotype had no influence on these associations. No correlation between BA levels and HCV RNA was detected for any HCV genotype. The higher allelic frequency of ABCB11 1331C in HCV-patients compared to controls may indirectly link increased BA to HCV chronicity. Our data support a role for BA as host factor affecting therapy response in HCV-2/3 patients, whereas a weaker association was found for HCV-1.

Antecedents, psychiatric characteristics and follow-up of adolescents hospitalized for suicide attempt of overwhelming suicidal ideation.

To evaluate the socio-demographic as well as the health and psychiatric profiles of adolescents hospitalised for suicide attempt or overwhelming suicide ideation and to assess repetition of suicide attempt over a period of 18 months. Between April 2000 and September 2001, all patients aged 16 to 21 years admitted to the University Hospitals of Geneva and Lausanne for suicide attempt or ideation were included in the study. At this time (T0) semi-structured face to face interviews were conducted to identify socio-demographic data, mental health and antecedents regarding suicidal conducts. Current psychiatric status was assessed with the MINI (Mini International Neuropsychiatric Instrument). At T1 and T2, reassessments included psychiatric status (MINI) as well as lifestyles, socio-professional situation and suicidal behaviours. At T0, 269 subjects met the study criteria, among whom 83 subjects (56 girls and 27 boys) left the hospital too quickly to be involved or refused to participate in the study (final sample at T0: 149 girls; 37 boys). The participation rate at T1 and T2 was respectively 66% and 62% of the original sample. The percentage of adolescents meeting the criteria for psychiatric diagnoses (91%) was high: affective disorder (78%); anxiety disorder (64%); substance use disorder (39%); eating disorder (9%); psychotic disorder (11%); antisocial personality (7%) with most subjects (85%) having more than one disorder. Around 90% of the subjects interviewed at T1, and/or T2, had received follow-up care after their hospitalisation, either by a primary care physician or a psychotherapist or both. Two subjects died of violent death and 18% made a further suicide attempt. Most adolescents hospitalised for suicidal episodes suffer from psychiatric problems which should be addressed by a careful psychiatric assessment, followed up if needed by a structured after care plan.

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise.

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.

The profiling of MDMA tablets: a study of the combination of physical characteristics and organic impurities as sources of information

The profiling of MDMA tablets can be carried out using different sets of characteristics. The first type of measurements performed on MDMA tablets are physical characteristics (i.e. post-tabletting characteristics). They yield preliminary profiling data that may be valuable in a first stage for investigation purposes. However organic impurities (i.e. pre-tabletting characteristics) are generally considered to bring more reliable information, particularly for presentation of evidence in court. This work aimed therefore at evaluating the added value of combining pre-tabletting characteristics and post-tabletting characteristics of seized MDMA tablets. In approximately half of the investigated cases, the post-tabletting links were confirmed with organic impurities analyses. In the remaining cases, post-tabletting batches (post-TBs) were divided in several pre-tabletting batches (pre-TBs), thus supporting the hypothesis that several production batches of MDMA powder (pre-TBs) were used to produce one single post-TB (i.e. tablets having the same shape, diameter, thickness, weight and score; but different organic impurities composition). In view of the obtained results, the hypotheses were discussed through illustrating examples. In conclusion, both sets of characteristics were found relevant alone and combined together. They actually provide distinct information about MDMA illicit production and trafficking.

Predicting outcome after acute basilar artery occlusion based on admission characteristics.

OBJECTIVE: To develop a simple prognostic model to predict outcome at 1 month after acute basilar artery occlusion (BAO) with readily available predictors. METHODS: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational, international registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO. We considered predictors available at hospital admission in multivariable logistic regression models to predict poor outcome (modified Rankin Scale [mRS] score 4-5 or death) at 1 month. We used receiver operator characteristic curves to assess the discriminatory performance of the models. RESULTS: Of the 619 patients, 429 (69%) had a poor outcome at 1 month: 74 (12%) had a mRS score of 4, 115 (19%) had a mRS score of 5, and 240 (39%) had died. The main predictors of poor outcome were older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIH Stroke Scale (NIHSS) score, and longer time to treatment. A prognostic model that combined demographic data and stroke risk factors had an area under the receiver operating characteristic curve (AUC) of 0.64. This performance improved by including findings from the neurologic examination (AUC 0.79) and CT imaging (AUC 0.80). A risk chart showed predictions of poor outcome at 1 month varying from 25 to 96%. CONCLUSION: Poor outcome after BAO can be reliably predicted by a simple model that includes older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIHSS score, and longer time to treatment.