TASTE Trial Research Articles

STK11/LKB1 alterations worsen the poor prognosis of KRAS mutated early-stage non-squamous non-small cell lung carcinoma, results based on the phase 2 IFCT TASTE trial

BackgroundSTK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This study aimed to assess the prognostic significance of STK11/LKB1 alterations in localized non-squamous non-small cell lung carcinoma (non-sq NSCLC). Patients and methodsSurgical samples from patients undergoing complete resection for stage IIa, IIb, or IIIa (N2 excluded) non-sq NSCLC in the randomized adjuvant phase II trial (NCT00775385 IFCT-1801 TASTE trial) were examined. Patients received either standard chemotherapy (Pemetrexed Cisplatin) or personalized treatment based on EGFR mutation (Erlotinib) and ERCC1 expression. Tumor molecular profiles were analyzed using targeted NGS and correlated with overall survival (OS) and disease-free survival (DFS), adjusting for relevant clinical variables. Additionally, interactions between treatment groups and molecular alterations on OS, PD-L1 expression, and tumor-circulating DNA in post-operative plasma samples were evaluated. ResultsAmong 134 patients (predominantly male smokers with adenocarcinoma), KRAS mutations were associated with shorter DFS (HR: 1.95, 95 % CI: 1.1–3.4, p = 0.02) and OS (HR: 2.32, 95 % CI: 1.2–4.6, p = 0.014). Isolated STK11/LKB1 mutations (n = 18) did not significantly impact DFS or OS. However, within KRAS-mutated samples (n = 53), patients with concurrent STK11/LKB1 mutations (n = 10) exhibited significantly shorter DFS (HR: 3.85, CI: 1.5–10.2, p = 0.006) and a trend towards shorter OS (HR: 1.80, CI: 0.6–5.3, p = 0.28). No associations were found between PD-L1 expression, other gene mutations, progression-free survival (PFS), or OS. ConclusionThis analysis reinforces KRAS mutations as predictive factors for relapse and poor survival in localized non-sq NSCLC. Furthermore, the presence of concomitant STK11/LKB1 mutations exacerbated the prognosis within the KRAS-mutated subset. These findings emphasize the clinical relevance of these molecular markers and their potential impact on treatment strategies in non-sq NSCLC.

Cost-effectiveness of edaravone dexborneol versus human urinary kallidinogenase for acute ischemic stroke in China

BackgroundClinical trials have demonstrated the efficacy of edaravone dexborneol in the treatment of acute ischemic stroke. This study aims to determine the cost-effectiveness of edaravone dexborneol compared with human urinary kallidinogenase from China’s healthcare system perspective.MethodsA combination of the decision tree and Markov model was constructed to evaluate the cost-effectiveness of edaravone dexborneol versus human urinary kallidinogenase in the treatment of acute ischemic stroke over a lifetime horizon. Efficacy data were derived from pivotal clinical trials of edaravone dexborneol and human urinary kallidinogenase (TASTE trial and RESK trial, respectively) and adjusted using matching-adjusted indirect comparison. Cost and health utility inputs were extracted from published literature and open databases. One-way deterministic sensitivity and probabilistic sensitivity analyses were performed to examine the robustness of the results.ResultsCompared with human urinary kallidinogenase, edaravone dexborneol generated 0.153 incremental quality-adjusted life years (QALYs) with an incremental cost of ¥856, yielding an incremental cost-effectiveness ratio of ¥5,608 per QALY gained under the willingness-to-pay threshold (one-time gross domestic product per capita). Both one-way deterministic sensitivity analysis and probabilistic sensitivity analysis demonstrated the robustness of the base case results.ConclusionsEdaravone dexborneol is a cost-effective treatment choice for acute ischemic stroke patients compared with human urinary kallidinogenase in China.

Smell and taste of milk during tube feeding of preterm infants: neurodevelopmental follow-up of the randomized TASTE trial, study protocol

BackgroundThe Taste And Smell To Enhance nutrition (TASTE) trial investigated the effects of smell and taste of milk with tube feeding compared to routine care on the growth of preterm infants. There was no difference between groups in growth (weight, head circumference, length) z-scores at discharge from the hospital. Infants in the intervention group had higher head circumference and length z-scores at 36 weeks postmenstrual age, both secondary outcomes. The objective of this follow-up study is to assess 2-year neurodevelopmental and growth outcomes after exposure of preterm infants to the smell and taste of milk with tube feeding compared to routine care.MethodsThis is a neurodevelopmental follow-up study of a two-center, placebo-controlled randomized trial. Infants born before 29 weeks postmenstrual age and/or with a birth weight of less than 1250 g were randomized to smell and taste of milk with each tube feed or routine care. The current follow-up assessed the 2-year neurodevelopmental and growth outcomes of participants of the TASTE trial discharged from the hospital (n = 334). The primary outcome is survival free of any major neurodevelopmental impairment comprising any moderate/severe cerebral palsy (Gross Motor Function Classification System score II–V), Bayley Scales of Infant and Toddler Development, Third/Fourth Edition (Bayley-III/Bayley-4) motor, cognitive, or language scores < -2SD, blindness, or deafness at 2 years of age. Other outcomes include death, breastfeeding within the first year, and respiratory support, oral feeding, and anthropometric parameters at 2 years of age. The Human Research Ethics Committees of Mater Misericordiae Limited and the Royal Women’s Hospital approved the TASTE trial including the neurodevelopmental follow-up described in this protocol.DiscussionFor patients and their families, the neurodevelopmental outcomes of preterm infants are of utmost importance. Consequently, they should be investigated following any interventional study performed during the newborn period. Furthermore, improved weight gain and head growth in the hospital are associated with better long-term neurodevelopmental outcomes. Smelling and tasting of milk is an uncomplicated and cost-effective intervention that may improve the growth and neurodevelopmental outcomes of preterm infants. Potential limitations affecting this follow-up study, caused by the COVID-19 pandemic, are anticipated and discussed in this protocol.Trial registrationName of the registry: Australian and New Zealand Clinical Trials Registry; Registration number: ACTRN12617000583347; Registration date: 26 April 2017.

Registry randomized controlled trials: the future of surgical trials?

Registry randomized controlled trials: the future of surgical trials?

Cost-effectiveness of edaravone dexborneol versus edaravone for the treatment of acute ischemic stroke in China: Based on the TASTE study.

Background and purpose: The TASTE trial indicated that patients with acute ischemic stroke (AIS) using edaravone dexborneol have a significantly higher proportion of 90-day good functional outcomes (mRS 0-1) than those using edaravone. This study compared the cost-effectiveness of the aforementioned interventions in treating AIS in the Chinese setting, aiming to inform treatment decisions in clinical practice. Methods: A model combining a decision tree and a Markov model was developed to assess the cost-effectiveness of edaravone dexborneol versus edaravone for AIS over a 30-year time horizon from the Chinese healthcare system's perspective. Both efficacy and safety data were extracted from the TASTE study. Local costs and utilities were derived from publications and open-access databases; both cost and effectiveness were discounted at a rate of 5% per year. Sensitivity analyses were conducted to ensure robustness and identify the main drivers of the result. Results: Compared with edaravone, edaravone dexborneol for AIS was found to be cost-effective in the first year and highly cost-effective as the study time horizons extended. In the long term (30 years), edaravone dexborneol yielded a lifetime gain of 0.25 (0.07-0.45) quality-adjusted life years (QALYs) at an additional cost of CNY 2201.07 (-3,445.24-6,637.23), yielding an ICER of CNY 8823.41 per QALY gained under the willingness-to-pay (WTP) of 1.5 times per capita GDP (121,464 CNY). The result is robust in both deterministic and probabilistic sensitivity analysis (PSA) methods, with the advantage of the edaravone dexborneol strategy increasing over time. Specifically, the probability of edaravone dexborneol dominant dexborneol is 76.30%, 98.90%, and 99.50% over 1-, 5-, and 30-year time horizons. Conclusion: Both short- and long-term economic analyses suggest that edaravone dexborneol is highly likely to be a cost-effective alternative to treat AIS compared with edaravone in China.

Benchmarking Observational Analyses Before Using Them to Address Questions Trials Do Not Answer: An Application to Coronary Thrombus Aspiration.

To increase confidence in the use of observational analyses when addressing effectiveness questions beyond those addressed by randomized trials, one can first benchmark the observational analyses against existing trial results. We used Swedish registry data to emulate a target trial similar to the Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) randomized trial, which found no difference in the risk of death or myocardial infarction by 1 year with or without thrombus aspiration among individuals with ST-elevation myocardial infarction. We benchmarked the emulation against the trial at 1 year and then extended the emulation’s follow-up to 3 years and estimated effects in subpopulations underrepresented in the trial. As in the TASTE trial, the observational analysis found no differences in risk of outcomes by 1 year between groups (risk difference = 0.7 (confidence interval, −0.7, 2.0) and −0.2 (confidence interval, −1.3, 1.0) for death and myocardial infarction, respectively), so benchmarking was considered successful. We additionally showed no difference in risk of death or myocardial infarction by 3 years, or within subpopulations by 1 year. Benchmarking against an index trial before using observational analyses to answer questions beyond those the trial could address allowed us to explore whether the observational data can be trusted to deliver valid estimates of treatment effects.

Registries: Big data, bigger problems?

Patient registries have grown in size and number along with general computing power and digitization of the healthcare world. In contrast to databases, registries are typically patient data systematically created and collected for the express purpose of answering health-related questions. Registries can be disease-, procedure-, pathology-, or product-based in nature. Registry-based studies typically fit into Level II or III in the hierarchy of evidence-based medicine. However, a recent advent in the use of registry data has been the development and execution of registry-based trials, such as the TASTE trial, which may elevate registry-based studies into the realm of Level I evidence. Some strengths of registries include the sheer volume of data, the inclusion of a diverse set of participants, and their ability to be linked to other registries and databases. Limitations of registries include variable quality of the collected data, and a lack of active follow-up (which may underestimate rates of adverse events). As with any study type, the intended design does not automatically lead to a study of a certain quality. While no specific tool exists for assessing the quality of a registry-based study, some important considerations include ensuring the registry is appropriate for the question being asked, whether the patient population is representative, the presence of an appropriate comparison group, and the validity and generalizability of the registry in question. The future of clinical registries remains to be seen, but the incorporation of big data and machine learning algorithms will certainly play an important role.

Abstract P148: Safety And Efficacy Of Edaravone Dexborneol Versus Edaravone Alone For The Treatment Of Acute Ischemic Stroke Patients With Hypertention: Analysis From Taste Trial

Background and Aims: Evidenced by TASTE phase III trial, 90-day good functional outcomes favored the edaravone dexborneol group versus edaravone group when administered within 48 hours after Acute Ischemic Stroke (AIS). The present study aimed to investigate the effects of edaravone dexborneol versus edaravone in AIS patients with hypertension medical history. Methods: This study was a subgroup analysis of the TASTE trial with hypertension medical history. The primary outcome was the proportion of patients with modified Rankin Scale (mRS) score ≤1 on day 90 after randomization. The secondary outcome was the mRS score on day 90. The safety endpoints were the incidences of adverse events, serious adverse events and deaths. Analyses were by intention to treat. Results: We included 767 AIS patients with hypertension (390 in edaravone dexborneol group, 377 in edaravone group) in this analysis. Among them, 252 (64.62%) in edaravone dexborneol group versus 199 (52.79%) in edaravone group reached mRS score ≤1 on D90, revealing significantly higher proportion of mRS score ≤1 on D90 in edaravone dexborneol group (OR 1.63 [95% CI, 1.22-2.18]; P&lt;0.001). Significant differences occurred between two groups in mRS score on D90 ([OR 1.32 [95% CI, 1.02-1.72]; P=0.038). The safety outcomes indicated that the two groups were similar in incidences of adverse events (366 [93.85%] versus 352 [93.37%], p=0.787), serious adverse events (48 [12.31%] versus 34 [9.02%], p=0.1405) and number of deaths (6 [1.54%] versus 4 [1.06%], p=0.56). Conclusion: This analysis demonstrated that AIS patients with hypertension receiving edaravone dexborneol had better functional outcomes than those with edaravone, which provided evidences for the clinical application of edaravone dexborneol in AIS patients with hypertension. Keywords: Edaravone dexborneol, Acute ischemic stroke, Hypertension, mRS score

Prior administration of chocolate improves the palatability of bitter drugs: The Choc-with-Med study.

The paediatric population has a low adherence and acceptance rate of unpalatable medicines. This study aimed to determine whether eating chocolate immediately prior to drug administration would help to mask the bitter taste of a drug. The difference in taste masking efficacy between white, milk and dark chocolate was a secondary measure outcome. A controlled repeated measures crossover taste trial was conducted using a taste panel of 29 young healthy adults who met the criteria to differentiate intensity in bitterness taste. Participants separately tasted solutions of quinine, flucloxacillin and clindamycin using the swill and spit method, singularly and following blinded prior administration of white, milk or dark chocolate. Drug solutions administered without prior chocolate served as controls. Bitterness score for each tasting was recorded using a 5-point scale. Regardless of chocolate type, mean taste scores with prior chocolate for quinine (range 2.00-2.34), clindamycin (3.72-3.83) and flucloxacillin (3.38-3.45) were all lower than mean scores for respective drugs without chocolate (3.24, 4.75 and 4.28, respectively; P < 0.0001 for all comparisons). Dark chocolate was most efficacious for masking the bitter taste of quinine, but the differences in taste masking efficacy between dark, milk and white chocolates were not statistically significant for flucloxacillin and clindamycin. Prior administration of chocolate results in lower perceived bitterness compared to control tastings of quinine, flucloxacillin and clindamycin solutions; however, there is no clear difference in this effect between the dark, milk and white chocolates used in this study.

Growth, integrity, and consumer acceptance of largemouth bass, Micropterus salmoides (Lacépède, 1802), fed marine resource-free diets

Largemouth bass (LMB) were fed diets developed to substitute fishmeal (FM) using a blend of alternative proteins. Diets included a FM control (FMC), two FM-free formulæ (FMF), one of which (FFF) was formulated using an algal oil replacing fish oil (FO) and, for comparative purposes, a commercial LMB feed (COM). Fish (densities of 3.11±0.29 kg m-1) were arbitrarily distributed into one of eight tanks configured as a recirculating system (RAS; 28.3±0.76 oC; DO2: 7.7±1.19 mg L-1) and tanks randomly assigned to one of the four treatments (i.e. each treatment was tested in duplicate). Animals were fed 3x daily to apparent satiation and group weighed every 3 weeks for 18 weeks. No differences were observed in feed consumption between groups (P >0.05) but LMB fed the COM diet were heavier (P< 0.05) than fish fed the FMF and FFF feeds. In efforts to verify whether fish fed the FM/FO-free were authentic, samples were assessed by stable isotope ratio mass spectrometry. δ15N fish muscle isotope values at trial end were indicative of dietary FM substitution. A preliminary blind taste trial undertaken using fish from the FFF and COM diets did not differentiate between treatments (P > 0.05). Results from the present study show that, with prudent dietary control, complete replacement of FM/FO in LMB diets is attainable and verifiable, without compromising growth performance or consumer acceptance of the final product.

Taste Responses in the Nucleus of the Solitary Tract of Awake Obese Rats Are Blunted Compared With Those in Lean Rats.

Taste perception changes with obesity but the underlying neural changes remain poorly understood. To address this issue, we recorded taste responses from single cells in the nucleus tractus solitarius (NTS, the first synapse in the central gustatory circuit) in awake, diet-induced obese [(DIO; ≥ 8 weeks on a high-energy diet (45%fat, 17% sugar; HED)], and lean rats. Rats were implanted with a bundle of microelectrodes in the NTS and allowed to recover. Water-deprived rats were allowed to freely lick various tastants in an experimental chamber. Taste stimuli included an array of sapid stimuli dissolved in artificial saliva (AS). Each taste trial consisted of five consecutive licks followed by five AS licks presented on a VR5 schedule. Results showed that taste responses (n = 49 for DIO; n = 74 for lean rats) in NTS cells in DIO rats were smaller in magnitude, shorter in duration, and longer in latency that those in lean rats. However, there were proportionately more taste-responsive cells in DIO than in lean rats. Lick coherence in DIO rats was significantly lower than in lean rats, both in taste-responsive, and lick-related cells (n = 172 in lean; n = 65 in DIO). Analyses of temporal coding showed that taste cells in DIO rats conveyed less information about taste quality than cells in lean rats. Collectively, results suggest that a HED produces blunted, but more prevalent, responses to taste in the NTS, and a weakened association of taste responses with ingestive behavior. These neural adaptations may represent both negative effects and compensatory mechanisms of a HED that may underlie deficits in taste-related behavior associated with obesity.

The effect of smell and taste of milk during tube feeding of preterm infants (the Taste trial): a protocol for a randomised controlled trial

IntroductionSmell and taste of milk are not generally considered when tube feeding preterm infants. Preterm infants have rapid growth, particularly of the brain, and high caloric needs. Enteral feeding is...

Impact of taste and smell training on taste disorders during chemotherapy - TASTE trial.

PurposeTwo-thirds of cancer patients report taste disorders during and after chemotherapy. Taste disorders impact on nutritional status which is highly relevant for treatment efficacy and overall prognosis. Improvement of taste disorder is of particular importance for cancer patients’ outcomes, thus the TASTE trial was conducted to improve taste disorders with a taste and smell training.MethodsIn this trial, patients undergoing chemotherapy were screened for taste disorders. Subsequently, patients were allocated based on the detection of taste disorders (≤8 taste strips points) to an intervention group with a taste and smell training at baseline and week 3–5 or were only followed up, if no taste disorder was detected (≥9 taste strips points) (non-intervention group). At baseline, all patients received a nutritional counseling. The primary endpoint was the minimal clinically relevant improvement of taste strips score by 2 taste strips points in at least 50% of the patients with taste disorders.ResultsThe trial included 62 patients (48 women [77%], 14 male [23%], age 54.5±11.6 years) who had gastrointestinal (n=29), breast (n=31), or lung cancer (n=2). Taste disorders were more frequent in gastrointestinal than in breast cancer patients. Out of 62 patients screened, 30 patients showed taste disorders. The primary endpoint was met with 92% (n=23 of 25) of the patients completing the intervention. In the intervention group, the patients’ taste significantly improved from baseline (median taste strips: 7.0 points) to week 12 (median taste strips: 10.0 points) (P≤0.001). Patients of the non-intervention group who completed the reassessment (n=27 of 32) experienced no change in taste perception in the 3-month follow-up (P=0.897).ConclusionIntensified nutritional counseling with taste and smell training may improve taste perception of patients undergoing chemotherapy. A confirmatory randomized trial is planned.

Development and Acceptability of Locally Made Fish-Based, Ready-to-Use Products for the Prevention and Treatment of Malnutrition in Cambodia.

Cambodia has a high prevalence of moderate acute malnutrition and severe acute malnutrition (SAM). The SAM treatment requires ready-to-use therapeutic foods (RUTFs), whereas ready-to-use supplementary foods (RUSFs) are used for prevention of acute malnutrition. Three locally produced fish-based products were developed: an RUTF paste (NumTrey-Paste) for treatment and 2 wafer versions, one for prevention (NumTrey-RUSF) and one for treatment (NumTrey-RUTF). To assess the acceptability of NumTrey-Paste and NumTrey-RUSF in comparison to a standard biscuit product (BP-100) used for the treatment of SAM. Acceptability of NumTrey-RUSF and NumTrey-Paste was tested in a nonblinded crossover taste trial among children (n = 52), aged ≥ 6 months to 18 years, and their caregivers. Eight organoleptic qualities were assessed on a 5-point hedonic scale, as well as a ranking test. A score of 1 to 3 was categorized as acceptable. The acceptability of NumTrey-RUTF was assessed using the caregivers' perception during an SAM treatment intervention. Taste trial: The proportion of children categorizing products as overall acceptable was lowest for NumTrey-Paste compared to for BP-100 and NumTrey-RUSF (21% vs 43% [BP-100] and 36% [NumTrey-RUSF]). No difference was found in the proportion of children who ranked BP-100 or NumTrey-RUSF as "liked most" ( P > .05). Acceptability of NumTrey-RUSF ranked highest in appearance and taste (caregiver), whereas acceptability of NumTrey-Paste was ranked lowest in appearance and smell among the products. Intervention trial: The acceptability of NumTrey-RUTF increased from 72% to 86%. The overall acceptability was ranked lowest for a pure paste product. However, filling the paste into a wafer made the product more acceptable.

Editor's Choice- Heparin pre-treatment in patients with ST-segment elevation myocardial infarction and the risk of intracoronary thrombus and total vessel occlusion. Insights from the TASTE trial.

Pre-treatment with unfractionated heparin is common in ST-segment elevation myocardial infarction (STEMI) protocols, but the effect on intracoronary thrombus burden is unknown. We studied the effect of heparin pre-treatment on intracoronary thrombus burden and Thrombolysis in Myocardial Infarction (TIMI) flow prior to percutaneous coronary intervention in patients with STEMI. The Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial angiographically assessed intracoronary thrombus burden and TIMI flow, prior to percutaneous coronary intervention, in patients with STEMI. In this observational sub-study, patients pre-treated with heparin were compared with patients not pre-treated with heparin. Primary end points were a visible intracoronary thrombus and total vessel occlusion prior to percutaneous coronary intervention. Secondary end points were in-hospital bleeding, in-hospital stroke and 30-day all-cause mortality. Heparin pre-treatment was administered in 2898 out of 7144 patients (41.0%). Patients pre-treated with heparin less often presented with an intracoronary thrombus (61.3% vs. 66.0%, p<0.001) and total vessel occlusion (62.9% vs. 71.6%, p<0.001). After adjustments, heparin pre-treatment was independently associated with a reduced risk of intracoronary thrombus (odds ratio (OR) 0.73, 95% confidence interval (CI)=0.65-0.83) and total vessel occlusion (OR 0.64, 95% CI=0.56-0.73), prior to percutaneous coronary intervention. There were no significant differences in secondary end points of in-hospital bleeding (OR 0.84, 95% CI=0.55-1.27), in-hospital stroke (OR 1.17, 95% CI=0.48-2.82) or 30-day all-cause mortality (hazard ratio 0.88, 95% CI=0.60-1.30). Heparin pre-treatment was independently associated with a lower risk of intracoronary thrombus and total vessel occlusion before percutaneous coronary intervention in patients with STEMI, without evident safety concerns, in this large multi-centre observational study.

Wine consumers' subjective responses to wine mouthfeel and understanding of wine body

Wine mouthfeel is considered important for wine quality by experts, while consumers understanding of mouthfeel and the role of wine body in their wine choice is unknown. One experiment determined the influence of intrinsic wine mouthfeel on consumers' wine liking and emotions, and the other, how consumers understand the term wine body. The first experiment used a 2 astringency level×2 body level experimental design. The samples were base wine with; nothing added (control), added xanthan gum (for increased body), added grape seed extract (GSE, for increased astringency), and with both added xanthan gum and GSE. The consumer taste trial (n=112) indicated that wine with increased body did not influence wine liking and emotions; while increased astringency decreased liking and elicited more intense negative emotions. The second experiment examined consumers' knowledge of wine body through an online survey (n=136). Consumers described wine body most frequently using words such as flavour, fullness, and strength. Wine body was therefore understood by consumers predominantly as a holistic multi-sensory perception of flavour. Wine flavour was indicated by consumers to be the most important factor driving purchase decisions followed by balance of flavours and wine body. It is crucial that wine professionals carefully communicate wine characteristics to consumers to prevent possible misunderstandings such as the meaning of wine body and as a result better meet consumer expectations. In future, the term body may benefit from a clearer definition for academic research as well as industry.

OA06.05 Proteomic Analysis of ERCC1 Predicts Benefit of Platinum Therapy in NSCLC: A Reevaluation of Samples from the TASTE Trial

It is hypothesized that low or absent expression of the excision repair cross-complementation group 1 (ERCC1) protein predicts improved survival in NSCLC patients treated with platinum-based therapy. However, the International Adjuvant Lung Cancer Trial Collaborative Group concluded that current ERCC1 assessment methods are inadequate for clinical decision-making. Due to the unreliability of ERCC1 immunohistochemistry (IHC), the IFCT-0801 TASTE (Tailored Postsurgical Therapy in Early-Stage NSCLC) trial of adjuvant therapy for NSCLC was discontinued. We reevaluated a subset of samples from the TASTE trial using mass spectrometry-based proteomics to quantitate ERCC1 protein. We correlated ERCC1 proteomic status with survival after chemotherapy with cisplatin/pemetrexed and compared it to ERCC1 IHC ranking. Formalin-fixed, paraffin-embedded NSCLC tumor tissues were laser microdissected, solubilized, digested, and proteomically analyzed. A multiplexed, selected reaction monitoring mass spectrometric assay was used to quantitate levels of multiple proteins including ERCC1. The Kaplan-Meier method and univariate Cox analysis assessed overall survival (OS) and relapse-free survival (RFS). A chi-squared test compared binary proteomic levels of ERCC1 (detectable vs. undetectable) with the IHC status assessed using an anti-ERCC1 antibody (8F1) during the TASTE trial. Of 146 evaluable patients, 33 (22.6%) had undetectable ERCC1 by quantitative proteomics. Proteomics found no detectable ERCC1 protein in 8/36 (22.2%) IHC-positive patients nor in 8/22 (19.3%) IHC-indeterminate patients. ERCC1 was detected in 71/88 (80.7%) IHC-negative patients (range: 36-137 amol/μg total tumor protein). Undetectable ERCC1 by proteomics was prognostic of OS (hazard ratio [HR]: 5.45; p=0.031). In survival analyses of cisplatin-treated patients (n=122), only one of the 15 deaths occurred among the patients with undetectable ERCC1 protein. These patients had better OS than cisplatin-treated patients with detectable ERCC1, although the difference statistically nonsignificant (HR: 3.98; p=0.102). RFS was similar between patients with and without detectable ERCC1. GARFT protein (predictive of response to pemetrexed) was quantified in 100% of patients (range: 492-4006 amol/μg). The 10 cisplatin/pemetrexed-treated patients with GARFT levels >900 amol/μg had nonsignificantly worse OS than their counterparts with lower GARFT levels (p=0.08). Although underpowered to detect statistically significant survival differences, this study clearly demonstrates that quantitative proteomics can increase accuracy in identifying NSCLC patients who will respond to platinum-based therapy because they do not express ERCC1. Approximately 28% of such patients were misclassified by ERCC1 IHC in the TASTE trial. Clinicians should be aware that multiplexed quantitative proteomics can quantitate ERCC1 simultaneously with multiple clinically relevant proteins in lung tumors and small biopsies.

Hedonic Escalation: When Food Just Tastes Better and Better

Hedonic escalation is the increased liking of each additional bite of a palatable food. Hedonic escalation is more likely to occur when (1) a palatable food consists of a complex combination of flavors, and (2) a person is motivated to taste additional flavors on each successive bite. Consequently, hedonic escalation is more prevalent when people can identify more flavors (pilot study), attend to additional flavors on each taste trial (study 1), have an opportunity to identify an additional flavor on each taste trial (study 2), and isolate distinct flavors on each taste trial (study 3). Changes in hedonic escalation can be attributed to increased sensitization to flavors as opposed to changes in the rate of habituation (study 4). Hedonic escalation can also increase consumption (study 5) and influence food choices (study 6). Collectively, these studies show that hedonic escalation is enabled by the opportunity to identify an additional source of hedonic experience on each successive taste of a food.

ESUS and INTERACT.

In this edition of IJS new therapeutic opportunities are highlighted. First, a metanalysis of all the trials so far of tenectaplase versus alteplase for acute stroke thrombolysis using individual patient data, clearly tenectaplase has great promise as a more effective, and safer form of thrombolysis but phase III, level 1 evidence is required, such as may be generated from the ongoing TASTE trial. Second, interesting data from the embolic stroke of unknown embolic stroke of undetermined source (ESUS) global registry provides additional background for the opportunity for new interventions such as the novel oral anticoagulants (NOACS). They found about 1/6 of all ischemic strokes were in the ESUS category and that they generally were younger, had milder deficits, and were usually treated with antiplatelet agents. This should prime us for the results of such trials as RE-SPECT ESUS, and NAVIGATE ESUS. Those who have been following the INTERACT studies will be interested to see that a post hoc analysis of the entire data set for the use of heparin prophylactically for thromboembolic events within seven days of ICH had a poor outcome, a result which should influence clinical practice. Finally, our fascinating series profiling young stroke investigators from around the globe continues with the spotlight on Dar Dowlatshahi from Canada. We hope to see you at the coming World Stroke Congress!

Impact of thrombus aspiration during ST-Elevation Myocardial Infarction: a six month composite endpoint and risk of stroke analyses of the TASTE trial.

BackgroundRoutine thrombus aspiration during primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) did not reduce the primary composite endpoint in the “A Randomised Trial of Routine Aspiration ThrOmbecTomy With PCI Versus PCI ALone in Patients With STEMI Undergoing Primary PCI” (TOTAL) trial. We aimed to analyse a similar endpoint in “The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia” (TASTE) trial up to 180 days.MethodsIn TASTE, 7244 patients with STEMI were randomised to thrombus aspiration followed by PCI or to PCI alone. We analysed the quadruple composite endpoint of cardiovascular death, cardiogenic shock, rehospitalisation for myocardial infarction, or new hospitalisation for heart failure. Furthermore, an extended net-benefit composite endpoint including stent thrombosis, target vessel revascularization or stroke within 180 days was analysed.ResultsThe primary quadruple composite endpoint occurred in 8.7 % (316 of 3621) in the thrombus aspiration group compared to 9.3 % (338 of 3623) in the PCI alone group (hazard ratio (HR), 0.93; 95 % confidence interval (CI); 0.80 - 1.09, P = 0.36) and the extended net-benefit composite endpoint in 12.0 % (436) vs. 13.2 % (479) (HR, 0.90; 95 % CI; 0.79 - 1.03, P = 0.12). Stroke within 30 days occurred in 0.7 % (27) vs. 0.7 % (24) (HR, 0.89; 95 % CI; 0.51–1.54, P = 0.68).ConclusionsA large and an extended composite endpoint analysis from the TASTE trial did not demonstrate any clinical benefit of routine thrombus aspiration during PCI in patients with STEMI. There was no evidence of an increased risk of stroke with thrombus aspiration.