The REWRITE Study - REal-WoRld effectIveness of TrifluridinE/tipiracil in Patients with Previously Treated Metastatic Colorectal Cancer.

AIMS: In the pivotal RECOURSE trial, trifluridine/tipiracil improved survival outcomes in refractory metastatic colorectal cancer (mCRC), while demonstrating an acceptable toxicity profile. Routine clinical practice evidence is important to support the ongoing value of recently approved medicines. Our objective was to assess the utilisation patterns and real-world effectiveness of trifluridine/tipiracil in previously treated mCRC patients. MATERIALS AND METHODS: This was a retrospective observational study including consecutive patients who started trifluridine/tipiracil between 1 April 2018 and 30 September 2019 in the medical oncology departments of three major public hospitals in Portugal. The primary outcome measure was overall survival. Associations between overall survival and patient and tumour characteristics were assessed using multivariate Cox regression analyses. RESULTS: In total, 111 patients were included in the study, with a mean age of 64 years. From these, 45.9% received two prior lines of treatment, 47.8% had three or more previous lines of treatment and 83.6% had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at baseline. The median duration of trifluridine/tipiracil treatment was 3.7 cycles (95% confidence interval 3.4-4.1). Most patients (80.4%) remained on their planned dose throughout the trifluridine/tipiracil treatment period, fulfilling 100% relative dose intensity. The median overall survival in the total study cohort was 7.9 months (95% confidence interval 6.4-9.8) and the median progression-free survival was 3.4 months (95% confidence interval 3.2-3.9). The median overall survival was significantly higher in patients with a normal serum lactate dehydrogenase (LDH) level (median overall survival 11.2 months for [135, 205] IU/l LDH [95% confidence interval 8.2-NR] and 13.6 months for [205, 251] IU/l LDH [95% confidence interval 8.2-NR]) and in better fitted (ECOG = 0-1) patients (median overall survival 8.0 months; 95% confidence interval 6.7-10.0). The median time to worsening performance status was 6.2 months (95% confidence interval 5.0-8.0). Treatment discontinuation due to adverse events was low (3.1%). CONCLUSION: Our study confirms the effectiveness of trifluridine/tipiracil in real-life mCRC patients. Overall survival and progression-free survival outcomes are consistent with the efficacy profile reported in the earlier randomised RECOURSE clinical trial. Like other real-world studies, we found no additional safety concerns in the use of trifluridine/tipiracil.

Alexithymia may explain the relationship between autistic traits and eating disorder psychopathology.

BACKGROUND: Autistic people are disproportionately vulnerable to anorexia nervosa and other eating disorders (ED), and within the general population, autistic traits correlate with ED psychopathology. A putative mechanism which may underpin this heightened risk is alexithymia, a difficulty identifying and describing emotional states which is observed in both autism and ED. In two experiments with independent non-clinical samples, we explored whether alexithymia might mediate the heightened risk of eating psychopathology in individuals high in autistic traits. METHODS: Our first experiment used the PROCESS macro for SPSS to examine relationships between alexithymia (measured by the Toronto Alexithymia Scale (TAS-20)), autistic traits (autism quotient (AQ)), and eating psychopathology (Eating Attitudes Test (EAT-26)) in 121 participants. Our second experiment (n = 300) replicated and furthered this analysis by examining moderating effects of sex and controlling for anxiety and depression as covariates. We also included an additional performance-based measure of alexithymia, the Levels of Emotional Awareness Scale (LEAS). RESULTS: Study 1 suggested that TAS-20 scores mediated the relationship between heightened autistic traits and eating psychopathology. Replication and further scrutiny of this finding, in study 2, revealed that this mediation effect was partial and specific to the female participants in this sample. The mediation effect appeared to be carried by the difficulty identifying feelings subscale of the TAS-20, even when depression and anxiety were controlled for. LEAS scores, however, were not significantly related to autistic traits or eating psychopathology. LIMITATIONS: Cross-sectional data prevents any conclusions around the direction and causality of relationships between alexithymia, autistic traits, and eating psychopathology (alongside depression and anxiety), necessitating longitudinal research. Our non-clinical sample was predominantly Caucasian undergraduate students, so it remains to be seen if these results would extrapolate to clinical and/or autistic samples. Divergence between the TAS-20 and LEAS raises crucial questions regarding the construct validity of these measures. CONCLUSIONS: Our findings with respect to autistic traits suggest that alexithymia could partially explain the prevalence of ED in autistic people and may as such be an important consideration in the pathogenesis and treatment of ED in autistic and non-autistic people alike. Further research with clinical samples is critical to explore these ideas. Differences between men and women, furthermore, emphasize the importance of looking for sex-specific as well as generic risk factors in autistic and non-autistic men and women.

Mining EEG scalp maps of independent components related to HCT tasks.

This work presents an unsupervised mining strategy, applied to an independent component analysis (ICA) of segments of data collected while participants are answering to the items of the Halstead Category Test (HCT). This new methodology was developed to achieve signal components at trial level and therefore to study signal dynamics which are not available within participants' ensemble average signals. The study will be focused on the signal component that can be elicited by the binary visual feedback which is part of the HCT protocol. The experimental study is conducted using a cohort of 58 participants.

Accessory subscapularis muscle - A forgotten variation?

The quadrangular space is a space in the axilla bounded by the inferior margin of the teres minor muscle, the superior margin of the teres major muscle, the lateral margin of the long head of the triceps brachii muscle and the surgical neck of the humerus, medially. The axillary nerve (C5-C6) and the posterior circumflex humeral artery and veins pass through this space in order to supply their territories. The subscapularis muscle is situated into the scapular fossa and inserts itself into the lesser tubercle of the humerus, thus helping stabilize the shoulder joint. A supernumerary muscle known as accessory subscapularis muscle originates from the anterior surface of the muscle and usually inserts itself into the shoulder joint. It is a rare variation with few reports of its existence and incidence. We present a case of the accessory subscapularis muscle in a male cadaver fixated with a 10% formalin solution. The muscle passed anteriorly to the axillary nerve, thus, predisposing an individual to quadrangular space compression syndrome. We perform a review of the literature and address its clinical, anthropological and anatomical significance.

ERP correlates of error processing during performance on the Halstead Category Test.

The Halstead Category Test (HCT) is a neuropsychological test that measures a person's ability to formulate and apply abstract principles. Performance must be adjusted based on feedback after each trial and errors are common until the underlying rules are discovered. Event-related potential (ERP) studies associated with the HCT are lacking. This paper demonstrates the use of a methodology inspired on Singular Spectrum Analysis (SSA) applied to EEG signals, to remove high amplitude ocular and movement artifacts during performance on the test. This filtering technique introduces no phase or latency distortions, with minimum loss of relevant EEG information. Importantly, the test was applied in its original clinical format, without introducing adaptations to ERP recordings. After signal treatment, the feedback-related negativity (FRN) wave, which is related to error-processing, was identified. This component peaked around 250ms, after feedback, in fronto-central electrodes. As expected, errors elicited more negative amplitudes than correct responses. Results are discussed in terms of the increased clinical potential that coupling ERP information with behavioral performance data can bring to the specificity of the HCT in diagnosing different types of impairment in frontal brain function.

Potential of volatile compounds produced by fungi to influence sensory quality of coffee beverage.

Fungi are known producers of a large number of volatile compounds (VCs). Several VCs such as 2,4,6 trichloroanisole (TCA), geosmin and terpenes have been found in coffee beverages, and these compounds can be responsible for off-flavor development. However, few studies have related the fungal contamination of coffee with the sensory characteristics of the beverage. The aim of this research was to investigate the production of VCs by fungi isolated from coffee and their potential as modifiers of the sensory coffee beverage quality. Three species were isolated from coffee from the southwest of São Paulo state and selected for the study: Penicillium brevicompactum, Aspergillus luchuensis (belonging to section Nigri) and Penicillium sp. nov. (related to Penicillium crustosum). VCs produced by the fungal inoculated in raw coffee beans were extracted and tentatively identified by SPME-GC-MS. Different VCs that may interfere in the coffee beverage quality were detected in the raw coffee beans inoculated with these fungal species (mainly A. luchuensis). Oct-1-en-3-ol was detected in the raw coffee inoculated with A. luchuensis. This compound, which is characterized by earthy and moldy/mushroom aroma, can be related to negative characteristics of coffee beverage in sensory analysis. On the other hand, the presence of some fungal species in the coffee, even at a high percentage of infection, did not necessarily result in loss of the sensorial quality of the beverage, since the samples with a high infection of P. brevicompactum showed positive sensory evaluation.

Mechanisms of cisplatin ototoxicity: theoretical review.

INTRODUCTION: Cisplatin is an effective chemotherapeutic agent commonly used in the treatment of malignant tumours, but ototoxicity is a significant side effect. OBJECTIVES: To discuss the mechanisms of cisplatin ototoxicity and subsequent cell death, and to present the results of experimental studies. MATERIAL AND METHODS: We conducted a systematic search for data published in national and international journals and books, using the Medline, SciELO, Bireme, LILACS and PubMed databases. RESULTS: The nicotinamide adenine dinucleotide phosphate oxidase 3 isoform (also termed NOX3) seems to be the main source of reactive oxygen species in the cochlea. These reactive oxygen species react with other molecules and trigger processes such as lipid peroxidation of the plasma membrane and increases in expression of the transient vanilloid receptor potential 1 ion channel. CONCLUSION: Cisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence.

Clustering evoked potential signals using subspace methods.

This work proposes a clustering technique to analyze evoked potential signals. The proposed method uses an orthogonal subspace model to enhance the single-trial signals of a session and simultaneously a subspace measure to group the trials into clusters. The ensemble averages of the signals of the different clusters are compared with ensemble averages of visually selected trials which are free of any artifact. Preliminary results consider recordings from an occipital channel where evoked response P100 wave is most pronounced.

Management of uncommon hernias in cirrhotic patients.

BACKGROUND: Abdominal hernias are a common disease among cirrhotic patients, because of malnutrition and persistently high intra-abdominal pressure due to ascites. When tense ascites is present, life-threatening complications are likely to occur. In such cases, the morbidity and mortality rates are high. OBJECTIVE: We describe 3 cirrhotic patients with rare complicated hernias that needed surgical repair. We discuss optimal timing for surgical approaches and the necessity of ascites control before surgery, as well as the technical details of the procedures. METHOD: Review of hospital charts of selected rare cases of herniae in cirrhotic patients. CONCLUSION: Elective surgical approaches can treat even uncommon hernias in cirrhotic patients with good results.

Laparoscopic resection of left liver segments using the intrahepatic Glissonian approach.

BACKGROUND: Recent advances in laparoscopic techniques have resulted in growing indications for laparoscopic hepatectomy. However, this procedure has not been widely developed, and anatomic segmental liver resection is not currently performed due to difficulty controlling the segmental Glissonian pedicles laparoscopically. This study aimed to report a novel technique for laparoscopic anatomic resection of left liver segments using the intrahepatic Glissonian approach based on small incisions according to anatomic landmarks such as Arantius' and round ligaments. METHODS: Nine consecutive patients underwent laparoscopic liver resection using the intrahepatic Glissonian technique from April 2007 to June 2008. Five patients underwent laparoscopic bisegmentectomy 2-3, one laparoscopic left hemihepatectomy, two resections of segment 3, and one resection of segment 4. RESULTS: One patient required a blood transfusion. The mean operation time was 180 min (range, 120-300 min), and the median hospital stay was 3 days (range, 1-5 days). No patient had postoperative signs of liver failure or bile leakage. No postoperative mortality was observed. CONCLUSION: The main advantage of the intrahepatic Glissonian procedure over other techniques is the possibility of gaining a rapid and precise access to the left Glissonian sheaths facilitating left hemihepatectomy, bisegmentectomy 2-3, and individual resections of segments 2, 3, and 4. The authors believe that the intrahepatic Glissonian technique facilitates laparoscopic liver resection and may increase the development of segment-based laparoscopic liver resection.

Subspace techniques to remove artifacts from EEG: a quantitative analysis.

In this work we discuss and apply projective subspace techniques to both multichannel as well as single channel recordings. The single-channel approach is based on singular spectrum analysis(SSA) and the multichannel approach uses the extended infomax algorithm which is implemented in the opensource toolbox EEGLAB. Both approaches will be evaluated using artificial mixtures of a set of selected EEG signals. The latter were selected visually to contain as the dominant activity one of the characteristic bands of an electroencephalogram (EEG). The evaluation is performed both in the time and frequency domain by using correlation coefficients and coherence function, respectively.

Laparoscopic right hemihepatectomy for hepatolithiasis.

BACKGROUND: Liver resection is the definitive treatment for unilateral hepatolithiasis. Recently, laparoscopic major hepatectomias have become more common and are being performed in highly specialized centers. However, few laparoscopic liver resections for hepatolithiasis have been reported. Chen et al. reported two cases of laparoscopic left lobectomy for hepatolithiasis, but to our knowledge, right hepatectomy has never been reported to date. This video demonstrates technical aspects of a totally laparoscopic right hepatectomy in a patient with hepatolithiasis. METHODS: A 21-year-old woman with right-sided nonoriental primary intrahepatic stones was referred for surgical treatment. The operation followed four distinct phases: liver mobilization, dissection of the right portal vein and right hepatic artery, extrahepatic dissection of the right hepatic vein, and parenchymal transection with harmonic shears and linear staplers for division of segment 5 and 8 branches of the middle hepatic vein. No Pringles' maneuver was used. In contrast to liver resection for other indications, the right bile duct was enlarged and filled with stones. It was divided during parenchymal transection and left open. After removal of the surgical specimen, the biliary tree was flushed with saline until stone clearance, under radioscopic surveillance, was complete. The right hepatic duct then was closed with running suture. RESULTS: The operative time was 240 min, and the estimated blood loss was 120 ml, with no blood transfusion. The hospital stay was 5 days. At this writing, the patient is well and asymptomatic 7 months after the procedure. CONCLUSION: Laparoscopic liver resection is safe and feasible for patients with hepatolithiasis and should be considered for those suffering from intrahepatic stones. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00464-007-9666-1) contains supplementary material, which is available to authorized users.

Relationship between the presence of tonsilloliths and halitosis in patients with chronic caseous tonsillitis.

OBJECTIVE: To study the volatile sulphur compounds (VSC) halitometry profile in a population with chronic caseous tonsillitis (CCT) and halitosis and to evaluate the relationship between the presence of a tonsillolith and abnormal halitometry in this population. DESIGN: Clinical prospective non-randomised study. SUBJECTS AND METHODS: Forty-nine patients with halitosis and CCT, 17 male (35%) and 32 female (65%), were selected among patients referred for CO(2) laser cryptolysis. Anamnesis, physical examination and VSC halitometry were carried out. Halitometry values less than 150 ppb of VSC were considered normal. RESULTS: Patients were divided in two groups: Group A - normal halitometry (41 patients - 83.7%) and Group B - abnormal halitometry (8 patients - 16.3%). Halitometry results in Group B were 5.2 times (429%) higher than in Group A and the majority of the patients with abnormal halitometry presented with a tonsillolith at the moment of examination. A tonsillolith was present in 75% of the patients with abnormal halitometry and only 6% of patients with normal halitometry values. CONCLUSIONS: The presence of a tonsillolith represents a tenfold increased risk of abnormal VSC halitometry and can be considered as a predictable factor for abnormal halitometry in patients with CCT.

Greedy kernel PCA applied to single-channel EEG recordings.

In this work, we propose the correction of univariate single channel EEGs using a kernel technique. The EEG signal is embedded in its time-delayed coordinates obtaining a multivariate signal. A kernel subspace technique is used for denoising and artefact extraction. The proposed kernel method follows a greedy approach to use a reduced data set to compute a new basis onto which to project the mapped data in feature space. The pre-image of the reconstructed multivariate signal is computed and the embedding is reverted. The resultant signal is the high amplitude artifact which must be subtracted from the original signal to obtain a corrected version of the underlying signal.

Chagas disease.

Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi-infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite-induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.

Automatic removal of high-amplitude artefacts from single-channel electroencephalograms.

In this work, we present a method to extract high-amplitude artefacts from single channel electroencephalogram (EEG) signals. The method is called local singular spectrum analysis (local SSA). It is based on a principal component analysis (PCA) applied to clusters of the multidimensional signals obtained after embedding the signals in their time-delayed coordinates. The decomposition of the multidimensional signals in each cluster is achieved by relating the largest eigenvalues with the large amplitude artefact component of the embedded signal. Then by reverting the clustering and embedding processes, the high-amplitude artefact can be extracted. Subtracting it from the original signal a corrected EEG signal results. The algorithm is applied to segments of real EEG recordings containing paroxysmal epileptiform activity contaminated by large EOG artefacts. We will show that the method can be applied also in parallel to correct all channels that present high-amplitude artefacts like ocular movement interferences or high-amplitude low frequency baseline drifts. The extracted artefacts as well as the corrected EEG will be presented.

On the use of simulated annealing to automatically assign decorrelated components in second-order blind source separation.

In this paper, an automatic assignment tool, called BSS-AutoAssign, for artifact-related decorrelated components within a second-order blind source separation (BSS) is presented. The latter is based on the recently proposed algorithm dAMUSE, which provides an elegant solution to both the BSS and the denoising problem simultaneously. BSS-AutoAssign uses a local principal component analysis (PCA)to approximate the artifact signal and defines a suitable cost function which is optimized using simulated annealing. The algorithms dAMUSE plus BSS-AutoAssign are illustrated by applying them to the separation of water artifacts from two-dimensional nuclear overhauser enhancement (2-D NOESY) spectroscopy signals of proteins dissolved in water.

Blood-sucking lice may disseminate Trypanosoma cruzi infection in baboons.

Trypanosoma cruzi (Schyzotrypanum, Chagas, 1909), and Chagas disease are endemic in captive-reared baboons at the Southwest Foundation for Biomedical Research, San Antonio, Texas. We obtained PCR amplification products from DNA extracted from sucking lice collected from the hair and skin of T. cruzi-infected baboons, with specific nested sets of primers for the protozoan kinetoplast DNA, and nuclear DNA. These products were hybridized to their complementary internal sequences. Selected sequences were cloned and sequencing established the presence of T. cruzi nuclear DNA, and minicircle kDNA. Competitive PCR with a kDNA set of primers determined the quantity of approximately 23.9 +/- 18.2 T. cruzi per louse. This finding suggests that the louse may be a vector incidentally contributing to the dissemination of T. cruzi infection in the baboon colony.

Trypanosoma cruzi prolyl oligopeptidase Tc80 is involved in nonphagocytic mammalian cell invasion by trypomastigotes.

Trypanosoma cruzi is an intracellular protozoan parasite able to invade a wide variety of mammalian cells. To have access to the target organs/cells, the parasite must cross the basal laminae and the extracellular matrix (ECM). We previously characterized an 80-kDa proteinase (Tc80) secreted by the infective trypomastigotes that hydrolyzes native collagens and might be involved in infection by degrading ECM components. Here, we present evidence indicating a role for Tc80 in the invasion of nonphagocytic cells. Tc80 was classified as a member of the prolyl oligopeptidase (POP) family of serine proteases and was also found to hydrolyze fibronectin. Selective inhibitors for POP Tc80 were synthesized that blocked parasite entry into cells. Blockage occurred when trypomastigotes were preincubated with irreversible inhibitors but not after host cell preincubation, and the blockage correlated with inhibition of POP Tc80 activity in treated parasites. These data and the enzyme location inside a vesicular compartment close to the flagellar pocket, a specialized domain in endocytosis/exocytosis, strongly suggest a role for POP Tc80 in the maturation of parasite protein(s) and/or, after secretion, in a local action on parasite or host cell/ECM components required for invasion.

Human IgG1 and IgG4: the main antibodies against Triatoma infestans (Hemiptera: Reduviidae) salivary gland proteins.

The Triatoma infestans salivary gland proteins (TSGP) can induce local and systemic hypersensitivity reactions in humans. IgG antibodies against TSGP were present in higher levels in sera of Chagas disease patients, and in individuals living in triatomine-infested areas than in controls living in triatomine-free areas. TSGP-specific IgG1 was found in sera of Chagas patients, and of individuals living in triatomine-infested rural areas, and uniquely specific IgG4 was present in sera of Chagas patients living in triatomine-infested areas, reactive against TSGP. Unique specificities were not detected in sera of individuals reacting against the ubiquitous mosquito Culex quinquifasciatus saliva proteins (CSGP). In conclusion, IgG1 reactive against TSGP is the main antibody present in individuals living in the triatomine-infested study areas. Also, IgG4 is found in the sera of insect-transmitted Chagas disease patients living in study areas.