Anti epidermal growth factor receptor therapy in small bowel adenocarcinoma

Rationale:Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal cancer, thus limited data about treatment for advanced disease are available. The lack of specific guidelines has justified the use of therapeutic protocols usually applied in advanced colorectal cancer. Few and preliminary data have suggested possible clinical benefit from the use of target therapy such as bevacizumab and cetuximab.Patient concerns:We present the case of a young woman who was admitted to the emergency department for acute abdominal pain, nausea, and vomiting related to a jejunal stenosis.Diagnoses:An enteroscopy with jejunal biopsy showed poorly differentiated cancerous cells suggestive for primary intestinal cancer. There were no signs of metastatic disease at radiological evaluation. A jejunal resection was subsequently carried out and the diagnosis of mucinous adenocarcinoma of the jejunum was confirmed.Interventions:The computed tomography scan performed 1 month after surgery showed metastatic disease. Therefore, the patient received combined protocols of chemotherapy and either bevacizumab or the anti-epidermal growth factor receptor (EGFR) panitumumab.Outcomes:A partial response (PR) was achieved with Folfox plus panitumumab and a maintenance therapy with panitumumab is being conducted with a mild toxicity and a progression free survival of 19 months since the beginning of panitumumab.Lessons:This is, to the best of our knowledge, the first report in the literature of a patient with SBA who has benefitted from panitumumab with an overall survival of 83 months

The cost of space independence in P300-BCI spellers.

Background: Though non-invasive EEG-based Brain Computer Interfaces (BCI) have been researched extensively over the last two decades, most designs require control of spatial attention and/or gaze on the part of the user. Methods: In healthy adults, we compared the offline performance of a space-independent P300-based BCI for spelling words using Rapid Serial Visual Presentation (RSVP), to the well-known space-dependent Matrix P300 speller. Results: EEG classifiability with the RSVP speller was as good as with the Matrix speller. While the Matrix speller’s performance was significantly reliant on early, gaze-dependent Visual Evoked Potentials (VEPs), the RSVP speller depended only on the space-independent P300b. However, there was a cost to true spatial independence: the RSVP speller was less efficient in terms of spelling speed. Conclusions: The advantage of space independence in the RSVP speller was concomitant with a marked reduction in spelling efficiency. Nevertheless, with key improvements to the RSVP design, truly space-independent BCIs could approach efficiencies on par with the Matrix speller. With sufficiently high letter spelling rates fused with predictive language modelling, they would be viable for potential applications with patients unable to direct overt visual gaze or covert attentional focus

Attention is more than prediction precision [Commentary on target article]

A cornerstone of the target article is that, in a predictive coding framework, attention can be modelled by weighting prediction error with a measure of precision. We argue that this is not a complete explanation, especially in the light of ERP (event-related potentials) data showing large evoked responses for frequently presented target stimuli, which thus are predicted

A new method for detecting deception in Event Related Potentials using individual-specific weight templates [Abstract]

A new method called the weight template (WT) is proposed for classifying Event related potentials (ERPs) into deceiving and non-deceiving. In this study, EEG data from two P300-based lie detection experiments were analyzed to demonstrate the efficiency of the WT method in detecting deception. A comparison was made with a common method used to measure P300 presence, called Peak-to-Peak, which is believed to be more accurate than other methods in measuring P300 amplitudes [1, 2]. One experiment consisted of presenting participants with birth date stimuli and 12 participants were instructed to lie about their own birthday. The other experiment consisted of 15 participants who were instructed to lie about their first names [3]. Using simulated EEG data [4], Receiver Operating Characteristic (ROC) curves were also generated to examine the efficiency of the proposed method in detecting deception in low signal-to-noise ERPs. Typically, P300-based lie detection systems employ the P300 component to detect concealed information. They present three stimulus types: Probes (P), which represent concealed information or crime details and can be recognized only by the guilty person; Irrelevants (I), which are frequent and task (crime)-irrelevant, and Targets (T), which are irrelevant items, but participants are asked to do a task whenever they see a Target. For practical lie detection, the key comparison is between Probe and Irrelevant ERPs, since, for the nondeceiver, the former would be an Irrelevant. Importantly, the Probe for a deceiver typically generates a P300 ERP component, which is absent for the Irrelevant. The principle underlying the WT method is that as the Target stimulus is task-relevant, it will evoke a robust P300 pattern for each subject, which we hypothesize is characteristic in form and polarity of that individual's P300. Accordingly, this TERP can serve as an individual-specific template, with which to search for the Probe P300. Specifically, the difference between Tand IERPs was used as a template (i.e. effectively as a kernel) and this template was applied to Pand IERPs. Using such a template, with some pre-processing steps, we found that the WT achieved significantly better detection performance in comparison to Peak-to-Peak. In the names lie detection, the WT was able to detect deception for 93% in the guilty group compared with 80% by Peak-to peak. The false alarm rates using WT and Peak-to-Peak were 2% and 8% respectively. In the birthdays lie detection, hit rates were 50% using WT and 33% using Peak-to-Peak. The false alarm rates of both methods were 5%. ROC curve analysis also showed that in ERPs with high signal-to-noise ratio (SNR), both methods could detect deception successfully and almost equally. However, the WT performed better in ERPs with low SNR. We thus conclude that the WT is simple and very effective for detecting deception, even in ERPs with low SNR

Breakthrough percepts of famous names

Studies have shown that presenting own-name stimuli on the fringe of awareness in Rapid Serial Visual Presentation (RSVP) generates a P3 component and provides an accurate and countermeasure resistant method for detecting identity deception (Bowman et al., 2013, 2014). The current study investigates how effective this Fringe-P3 method is at detecting recognition of familiar name stimuli with lower salience (i.e., famous names) than own name stimuli, as well as its accuracy with multi-item stimuli (i.e., first and second name pairs presented sequentially). The results demonstrated a highly significant ERP difference between famous and non-famous names at the group level and a detectable P3 for famous names for 86% of participants at the individual level. This demonstrates that the Fringe-P3 method can be used for detecting name stimuli other than own-names and for multi-item stimuli, thus further supporting the method's potential usefulness in forensic applications such as in detecting recognition of accomplices. (c) 2021 Elsevier Ltd. All rights reserved.Peer reviewe

Risk stratification of neck lesions detected sonographically during the follow-up of differentiated thyroid cancer

Context: The European Thyroid Association (ETA) has classified post-treatment cervical ultrasound findings in thyroid cancer patients based on their association with disease persistence/recurrence. Objective: To assess this classification's ability to predict the growth and persistence of such lesions during active post-treatment surveillance of patients with differentiated thyroid cancer (DTC). Design: Retrospective, observational study Setting: Thyroid cancer center, large Italian teaching hospital. Patients: Center referrals (2005–2014) were reviewed and patients selected with pathologically confirmed DTC; total thyroidectomy, with or without neck dissection and/or radioiodine remnant ablation; abnormal findings on ≥2 consecutive post-treatment neck sonograms; subsequent follow-up consisting of active surveillance. Baseline ultrasound abnormalities (thyroid bed masses, lymph nodes) were classified according to the ETA system. Patients were divided into group S (those with ≥1 lesion classified as ‘suspicious’) and group I (‘indeterminate’ lesions only). We recorded baseline and follow-up clinical data through 30 June 2015. Main Outcomes: Patients with growth (> 3 mm, largest diameter) of ≥1 lesion during follow-up, patients with ≥1 persistent lesion at the final visit. Results: The cohort included 58 (9%) of the 637 DTC cases screened. A total of 113 lesions were followed (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 years), group I had significantly lower rates than group S of lesion growth (8% vs. 36%, p=0.01) and persistence (64% vs. 97%, p=0.014). Median time to scan normalization: 2.9 years. Conclusions: The ETA's evidence-based classification of sonographically detected neck abnormalities can help identify PTC patients eligible for more relaxed follow-up

Motivational intensity and visual word search : Layout matters

Motivational intensity has been previously linked to information processing. In particular, it has been argued that affects which are high in motivational intensity tend to narrow cognitive scope. A similar effect has been attributed to negative affect, which has been linked to narrowing of cognitive scope. In this paper, we investigated how these phenomena manifest themselves during visual word search. We conducted three studies in which participants were instructed to perform word category identification. We manipulated motivational intensity by controlling reward expectations and affect via reward outcomes. Importantly, we altered visual search paradigms, assessing the effects of affective manipulations as modulated by information arrangement. We recorded multiple physiological signals (EEG, EDA, ECG and eye tracking) to assess whether motivational states can be predicted by physiology. Across the three studies, we found that high motivational intensity narrowed visual attentional scope by altering visual search strategies, especially when information was displayed sparsely. Instead, when information was vertically listed, approach-directed motivational intensity appeared to improve memory encoding. We also observed that physiology, in particular eye tracking, may be used to detect biases induced by motivational intensity, especially when information is sparsely organised.Peer reviewe

RET mutation and increased angiogenesis in medullary thyroid carcinomas

Advanced medullary thyroid cancers (MTCs) are now being treated with drugs that inhibit receptor tyrosine kinases, many of which involved in angiogenesis. Response rates vary widely, and toxic effects are common, so treatment should be reserved for MTCs likely to be responsive to these drugs. RET mutations are common in MTCs, but it is unclear how they influence the microvascularization of these tumors. We examined 45 MTCs with germ-line or somatic RET mutations (RETmut group) and 34 with wild-type RET (RETwt). Taqman Low-Density Arrays were used to assess proangiogenic gene expression. Immunohistochemistry was used to assess intratumoral, peritumoral and nontumoral expression levels of VEGFR1, R2, R3, PDGFRa, PDGFB and NOTCH3. We also assessed microvessel density (MVD) and lymphatic vessel density (LVD) based on CD31-positive and podoplanin-positive vessel counts, respectively, and vascular pericyte density based on staining for a-smooth muscle actin (a-SMA), a pericyte marker. Compared with RETwt tumors, RETmut tumors exhibited upregulated expression of proangiogenic genes (mRNA and protein), especially VEGFR1, PDGFB and NOTCH3. MVDs and LVDs were similar in the two groups. However, microvessels in RETmut tumors were more likely to be a-SMA positive, indicating enhanced coverage by pericytes, which play key roles in vessel sprouting, maturation and stabilization. These data suggest that angiogenesis in RETmut MTCs may be more intense and complete than that found in RETwt tumors, a feature that might increase their susceptibility to antiangiogenic therapy. Given their increased vascular pericyte density, RETmut MTCs might also benefit from combined or preliminary treatment with PDGF inhibitors

Papillary thyroid carcinomas with biochemical incomplete or indeterminate responses to initial treatment: repeat stimulated thyroglobulin assay to identify disease-free patients

Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg ≥1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels ≤1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (<10 ng/mL). In unselected PTC cohorts with incomplete/indeterminate biochemical responses to thyroidectomy and RRA, periodic remeasurement of stimulated Tg allows most patients to be classified as disease-free