Aims: The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but ...genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC. Methods: A hospital-based case–control study was conducted in São Paulo, Brazil. We here investigated ADH1C Ile350Val, ADH1B Arg48His, ADH1B Arg370Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital. Results: Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg48His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21–0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20–0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13–0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg48His who consume alcohol >30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21–16.11). Conclusions: The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is <30.655 g/L/day.
Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall ...survival (OS) of only 25% to 33%.
STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab 1 mg/kg, every three weeks (Q3W) plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint.
Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months 95% confidence interval (CI) 7.0-not estimable (NE) versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively.
The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.
•First randomised trial comparing nivolumab/ipilimumab versus observation after standard chemo-radiotherapy and PCI in LD-SCLC.•Period on active treatment was short with a median time to nivolumab/ipilimumab discontinuation <2 months.•No improvement for PFS and OS for immunotherapy consolidation over observation.•Higher OS benefit observed for patients on twice daily radiotherapy schedule (versus once daily), female sex and ECOG PS 1.
The physical and chemical properties of tris(8-hydroxyquinolinato)aluminum (Alq3), one of the organic materials most commonly used as the light-emitting layer of OLEDs, and the interface with ...possible metal cathodes are investigated by means of first- principles computer simulations. A number of new insights have emerged from this study, and we emphasize the consequences of the properties thus discovered with respect to the functioning of OLED devices.
In this paper we report the experimental study of high-pressure xenon used as a scintillator, in the context of developing a gamma ray detector. We measure a light yield near 2 photoelectrons per keV ...for xenon at 40bar. Together with the light yield, we also measured an energy resolution of ∼9% (FWHM) at 662keV.
Liquid xenon (LXe) is an excellent material for experiments designed to detect dark matter in the form of weakly interacting massive particles (WIMPs). A low energy detection threshold is essential ...for a sensitive WIMP search. The understanding of the relative scintillation efficiency (L{sub eff}) and ionization yield of low energy nuclear recoils in LXe is limited for energies below 10 keV. In this article, we present new measurements that extend the energy down to 4 keV, finding that L{sub eff} decreases with decreasing energy. We also measure the quenching of scintillation efficiency caused by the electric field in LXe, finding no significant field dependence.
Molecular tumor profiling to identify oncogenic drivers and actionable mutations has a profound impact on how lung cancer is treated. Especially in the subgroup of non-small cell lung cancer (NSCLC), ...molecular testing for certain mutations is crucial in daily clinical practice and is recommended by international guidelines. To date, a standardized approach to identify druggable genetic alterations are lacking. We have developed and implemented a new diagnostic algorithm to harmonize the molecular testing of NSCLC.
In this retrospective analysis, we reviewed 119 patients diagnosed with NSCLC at the University Hospital Zurich. Tumor samples were analyzed using our standardized diagnostic algorithm: After the histological diagnosis was made, tissue samples were further analyzed by immunohistochemical stainings as well as the real-time PCR test Idylla™. Extracted DNA was further utilized for comprehensive genomic profiling (FoundationOne®CDx, F1CDx).
Out of the 119 patients were included in this study, 100 patients were diagnosed with non-squamous NSCLC (nsqNSCLC) and 19 with squamous NSCLC (sqNSCLC). The samples from the nsqNSCLC patients underwent testing by Idylla™ and were evaluated by immunohistochemistry (IHC). F1CDx analysis was run on 67 samples and 46 potentially actionable genomic alterations were detected. Ten patients received the indicated targeted treatment. The median time to test results was 4 days for the Idylla test, 5 days for IHC and 13 days for the F1CDx.
In patients with NSCLC, the implementation of a standardized molecular testing algorithm provided information on predictive markers for NSCLC within a few working days. The implementation of broader genomic profiling led to the identification of actionable targets, which would otherwise not have been discovered.
•Multiple methods have been integrated to generate an efficient algorithm for NSCLC diagnostics•No discordance has been detected between different sequencing methods•The use of a standardized molecular testing algorithm provided information on predictive markers for NSCLC within a few working days
The effect of baking and digestion on the allergenicity of wheat flour proteins has been studied. Pooled sera of patients suffering from food allergy to wheat products were tested for IgE binding to ...the proteins of the wheat dough and of the bread crumb and crust, before and after being in vitro digested. During in vitro digestion, the IgE binding protein components of the unheated dough tended to disappear, whereas a permanence of IgE recognition was evident for both the bread crumb and crust. This indicates that the baking process increases the resistance of the potential allergens of the wheat flour to proteolytic digestion, allowing them to reach the gastrointestinal tract, where they can elicit the immunological response. Therefore, the effects of baking must be carefully considered in studying food allergies to wheat products. Keywords: allergy, bread, baking, digestion, food processing, wheat proteins
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